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TRANSCRIPT
CONTRAST AGENTS IN MRI Lucie Paulet 15072013
1
Contents
1 A few definitions
2 Relaxation enhancing Contrast Agents
3 CEST Contrast Agents
4 Conclusion and Outlook
2
A few definitions hellip
3
What is contrast
bull In MRI relative difference of the signal intensity between two adjoining tissues
bull One possible definition
3
What is a Contrast Agent
bull Substance administered during MRI to
Enhance natural contrast
Obtain dynamic information
NB Unlike CArsquos in CT and Xray indirect effect
5
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Contents
1 A few definitions
2 Relaxation enhancing Contrast Agents
3 CEST Contrast Agents
4 Conclusion and Outlook
2
A few definitions hellip
3
What is contrast
bull In MRI relative difference of the signal intensity between two adjoining tissues
bull One possible definition
3
What is a Contrast Agent
bull Substance administered during MRI to
Enhance natural contrast
Obtain dynamic information
NB Unlike CArsquos in CT and Xray indirect effect
5
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
A few definitions hellip
3
What is contrast
bull In MRI relative difference of the signal intensity between two adjoining tissues
bull One possible definition
3
What is a Contrast Agent
bull Substance administered during MRI to
Enhance natural contrast
Obtain dynamic information
NB Unlike CArsquos in CT and Xray indirect effect
5
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
What is contrast
bull In MRI relative difference of the signal intensity between two adjoining tissues
bull One possible definition
3
What is a Contrast Agent
bull Substance administered during MRI to
Enhance natural contrast
Obtain dynamic information
NB Unlike CArsquos in CT and Xray indirect effect
5
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
What is a Contrast Agent
bull Substance administered during MRI to
Enhance natural contrast
Obtain dynamic information
NB Unlike CArsquos in CT and Xray indirect effect
5
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Why we need Contrast Agents bull Early 1980rsquos first use of
Contrast Agents
bull Sometimes distinction between region of interest and evironment is impossible
signals are cancelled by
space averaging tissue properties too
similar
6
[1]
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Characteristics
bull Ability to modify some aspect of the observables tissue property involved in image contrast
bull Tissue specificity
bull Reasonable clearing period
bull Low toxicity and stability
bull Long Shelf Life
7
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Contrast Mechanisms in MRI
bull Difference of proton density (cannot be modified)
bull Modification of T1 or T2 relaxation times
bull Susceptibility effects (T2)
bull Resonance Frequency Shifting
8
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
(Current) Classification of Contrast Agents
Magnetic Properties Biodistribution
Paramagnetic Superparamagnetic Diamagnetic (CEST)
Extracellular Intravascular (so called blood pool contrast agents) Tissue Specific
9
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Relaxation enhancing CAs
10
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Modification of Relaxation Times
bull Relaxivity defines the quality of a CA
ri = ∆(1Ti)
[C]
bull Modification of relaxation rate
Ri = Ri0 + ri [C]
11
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
How modifying Relaxation affects signal intensity
Assuming SE sequence
SI(C) = ρ (1- exp ( -(R1deg + r1C)TR)) exp(-(R2deg+r2C )TE)
Linear rise at low concentrations
saturation behaviour
T2 effects predominant at higher concentrations
12
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Paramagnetic Contrast Agents
bull Positive contrast (T1 enhanced)
bull Relaxation to relax water proton needs to encounter fluctuating field
bull Without Contrast Agents this means other
protons
bull But Melectron asymp 700 Mproton
13
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Paramagnetic Contrast Agents
bull Paramagnetic materials Unpaired outer electrons dipoles
bull large field fluctuations
bull If close enough to the Larmor frequency relaxation of neighbouring protons significantly modified
1T1 = (1T1)innersphere + (1T1)outersphere
14
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Chemical Structure
bull Most paramagnetic substances are toxic (ie Gadolinium)
Chelation to a ligand
bull Complex Binding is a reversible process
Excess of free compounds in case toxic ions are released
15
[2]
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Comparison of T1 and T2 weighted images with and without Contrast Agent
16
[3]
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Superparamagnetic Contrast Agents
bull Modify T2T2 (negative contrast)
bull nanoparticles
bull Most common used compound Iron Oxide
17
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Contrast Agent Nanoparticle
18
[4]
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
How it works
bull Superparamagnetic compound induces very large field inhomogeneities
bull Provoques dephasing of neighbouring protons (susceptibility effects)
bull Decreases T2 (T2)
19
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Limits of Relaxation Enhancing CArsquos
bull Toxicity
bull Low specifity
bull Mostly exogenous affect bulk water relaxation properties for contrast
20
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Chemical Exchange Saturation Transfer Contrast Agents
21
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
CEST Contrast Agents
bull Based on the notion of chemical shift
bull Works provided chemical exchange rate is in the right regime
bull PARACEST and DiaCEST
bull Advantage of PARACEST tissue contrast can be turned on and off
22
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Chemical Saturation Transfer Imaging
bull Exogenousendogenous compounds bull Selective saturation of exchangeable protons or
molecules
bull Saturation is transfered through Chemical Exchange
bull Indirectly detected through the water signal with modified sensitivity
23
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
2 Exchange Sites Model
24
[5]
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Limits of CEST CArsquos
bull B0 and B1 inhomogeneities especially at high magnetic fields
bull CEST pulse sequence should be a long rectangular pulse but usually succession of gaussian pulses
25
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Other Contrast Agents
26
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Other Contrast Agents
bull Possibility of using X-ray Contrast Agents in MRI
bull Multispectral magnetic resonance imaging agents
bull Biodegradable Gadolinium Compounds
27
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Conclusion and Outlook
28
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Conclusion and Outlooks
bull We have seen what contrast agents are
what main mechanisms are used today to design them
bull The physics behind Contrast Agents will not change
bull Progress to be made in the chemistry of contrast agents
29
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
30
Thank you for your attention
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
References General Concepts of Contrast Media
Papers
[1] A Sorensen A Tievsky L Ostergaard R Weisskoff B Rosen Contrast Agents in Functional MR Imaging JanuaryFebruary 1997 7 47-55
[2] WR Bauer K Schulten Theory of Contrast Agents in Magnetic Resonance Imaging Magnetic Resonance in Medicine 1992 26 16-39
[3] H Ersoy F Rybicki M Prince Contrast Agents for Cardiovascular MRI Contemporary Cardiology Cardiovascular Magnetic Resonance Imaging 237-253
[4] R Heindricl E Haacke Basic Physics of MR Contrast Agents and Maximization of Image Contrast JMRI 1993 3 137-148
[5] G Yan L Robinson P Hogg Magnetic resonance imaging contrast agents Overview and perspectives Radiography 2007 13 e5-e9
Books
[6] D Weishaupt V D Koumlchli B Marincek How Does MRI Work An Introduction to the Physics and Function of Magnetic Resonance Imaging second edition Berlin Springer 2008
31
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
Lecture Notes
[7]Atle Bjornerud The Physics of Magnetic Resonance Imaging FYS-KJM 4740 Lecture Notes march 2008
Videos
httpwwwyoutubecomwatchv=Osx8Ced9Eyw
T2 and T1 Contrast Agents
[8] C Cunningham T Arai P Yang M McConnell J Pauly S Conolly Positive Contrast Magnetic Resonance Imaging of Cells labeled with Magnetic Nanoparticleslaquo
[9] M Woods D Woessner A Sherry Paramagnetic lanthanide complexes as PARACEST agents for medical imaging Chemical Society Reviews April 11 2006
[10] R Lauffer Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging Theory and Design Chem Rev 199787901-927
[11] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced materials 2009 21 2133-2148
[12] S Mornet S Vasseur F Grasset E DugMagnetic nanoparticle design for medical diagnosis and therapyuet Journal of Materials Chemistry 2004142161-2175
[13] J Bulte D Kraitchman Iron oxide MR contrast agents for molecular and cellular imaging NMR Biomed 2004 17 484-499
32
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
34
CEST Contrast Agents
[15] R M Henkelman G J Stanisz S Graham Magnetization transfer in MRI a review
NMR in Biomedicine 2001 14 57-64
[16] A Vinogradov A Sherry RLenkinski CEST From basic principles to applications
challenges and opportunities Journal of Magnetic Resonance 2013 229 155-172
[17] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST)
ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14
February 2013 1 102-114
[18] K Ward A Aletras R S Balaban A New Class of Contrast Agents for MRI Based on
Proton Chemical Exchange Dependent Saturation Transfer (CEST) Journal of Magnetic
Resonance 2000 14379-87
Other Contrast Agents
[19] G Zabow A Koretsky J Moreland Design and fabrication of a micromachinedmultispectral
resonance imaging agent J Micromech Microeng 20 January 2009 19
[20] S Aime L Calabi L Biondi M Miranda S Ghelli L Paleari C Rebaudengo E Terreno Ipamidol
Exploring the Potential Use of a Well-Established X-Ray Contrast Agent for MRI Magnetic
Resonance in Medicine 2005 53 830-834
33
Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
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Image Credits [1] V Runge Clinical MRI Texas WB Saunders Company [2] httpwwwgoogledeimgresq=gadolinium+chelateampum=1ampclient=ubuntuampsa=Nampcha
nnel=fsamphl=enampbiw=1303ampbih=647amptbm=ischamptbnid=mg_2MAlsetAegMampimgrefurl=httpwwwsepsciencecomInformationArchiveFeatured-Articles450-IC-ICPMS-Analysis-of-Gadolinium-based-MRI-Contrast-Agentsampdocid=yiJhdkK40Ps4FMampimgurl=httpwwwsepsciencecomimagesArticlesIssues1011pFUNFSTEINFig-1jpgampw=1468amph=568ampei=pZvjUf_SHoKitAaErIGQDAampzoom=1ampiact=hcampvpx=169ampvpy=215ampdur=786amphovh=139amphovw=361amptx=204ampty=53amppage=1amptbnh=79amptbnw=200ampstart=0ampndsp=18ampved=1t429r1s0i85
[3 V Runge Clinical MRI Texas WB Saunders Company [4] ] H Bin Na I Song T Hyeon Inorganic Nanoparticles for MRI Contrast Agents Advanced
materials 2009 21 2133-2148 [5] F Kogan H Hariharan R Reddy Chemical Exchange Saturation Transfer (CEST) ImagingDescription of Technique and Potential Clinical Applications Curr Radiol Rep 14 February 2013 1 102-114
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