Download - MY CONFLICTS OF INTEREST ARE Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline
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MY CONFLICTSOF INTEREST ARE
Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline
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Advanced Angioplasty 2007
MRI in Ischemic Heart Disease
Stefan Neubauer, MD FRCP FACCProfessor of Cardiovascular Medicine
Department of Cardiovascular MedicineUniversity of Oxford
John Radcliffe HospitalOxford UK
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Imaging in Ischemic Heart DiseaseImaging in Ischemic Heart Disease
• Chest X-ray
• Echocardiography
• Nuclear scintigraphy
• Catheterisation
• Chest X-ray
• Echocardiography
• Nuclear scintigraphy
• Catheterisation
Resolution
Information Radiation
Invasiveness• Cardiac Cardiac MRMRII
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The Comprehensive Cardiac MR (CMR) ExaminationThe Comprehensive Cardiac MR (CMR) Examination
• Cardiac and great vessel anatomy
• Cardiac volumes and mass
• Global and regional contractile function
• Regional myocardial tissue perfusion
• Regional myocardial tissue characteristics:
Viability, oedema, inflammation, fibrosis, metabolism
• Coronary artery lumen, wall anatomy, blood flow
Goal: <30 min acquisition, <10 min post-processingGoal: <30 min acquisition, <10 min post-processing
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1. What CMR has to offer
2. CMR research in PCI
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Comprehensive CMR Study
• High resolution anatomy
• Global / regional function
• Regional perfusion
• Viability/Oedema/Fibrosis
• Coronary Angiography
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Horizontal long axis Vertical long axis
Cardiac Function: True-FISP MRI
Jane Francis, MR technologist,
University of Oxford Centre for Clinical MR Research
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Short axis Stack of short axes
+10mm +20mm +30mm +40mm
+50mm +60mm +70mm +80mm +90mm
Base
Apex
Simpson’s Rule
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HLA cinePre-vs. post-surgery MRI
pre postNorm
EDV (ml) 1423 167 77-195
EF (%) 3 54 56-78
Selvanayagam J et al, Circulation 2003
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Tissue Phase Mapping
Regional Tissue Contractility
3D Velocities: Radial, circumferential, longitudinal
Petersen S et al, Radiology 2005
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Dobutamine-Stress MR: 4-Chamber
rest 20 µg
40 µg30 µg
Nagel E et al, Circulation 1999
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Influence of image quality
0
10
20
30
40
50
60
70
80
90
100
good / very good moderate
sensitivity (DSE)
specificity (DSE)
sensitivity (DSMR)
specificity (DSMR)
E. Nagel, Z Kardiol 1999
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• High resolution anatomy
• Global / regional function
• Regional perfusion - GdDTPA
• Viability/Oedema/Fibrosis
• Coronary Angiography
Comprehensive CMR Study
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<10s
PerfusioPerfusionn
10-20 min
InfarctInfarct
[Gd]
time
“First pass” study: Time-intensity curves
Normal
Ischemia/Infarct
LV Blood pool
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Myocardial Perfusion - Quantification
Wilke N et al. MRM 1993
• Qualitative (eyeballing)
• Semi-quantification (upslope)
→ perfusion reserve
• Absolute quantification (ml/min x g)
Rest and stress perfusion(i.v. Adenosine 140g/kg x min)
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Regional Myocardial Perfusion
• n=84
• Prevalence of CAD 51%
• Sensitivity 88%
• Specificity 90%
• Diagnostic accuracy 89%
Nagel E el al. Circulation 2003
Wolff SD et al, Circulation 2004Giang TH et al, Eur Heart J 2004
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MR IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial)
A phase III multicenter, multivendor trial comparing perfusion cardiac magnetic resonance versus
single photon emission computed tomography for the detection of coronary artery disease.
J. Schwitter, 1 C. Wacker, 2 N. Wilke, 3 N. Al-Saadi, 4 N. Hoebel, 5 T. Simor 6
1 Zurich, Switzerland, 2 Würzburg, Germany, 3 Gainesville/Jacksonville, US 4 Berlin Germany, 5 Munich, Germany, GEHC, 6 Pecs, Hungary
• 33 centres, 1.5 Tesla, 465 patients• Patients with chest pain undergoing coronary angiography• CAD defined as >50% diameter stenosis in at least one vessel with at
least 2mm diameter
CardioVascularMR Center Zurich
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0
0.25
0.5
0.75
1
0 0.25 0.5 0.75 1
1-Specificity
MR-IMPACT II 33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA
*
Se
ns
itiv
ity
CardioVascularMR Center Zurich
SPECT all n=465 AUC: 0.65±0.03 P=0.0004
Perfusion-CMR n=465 AUC: 0.75±0.02
gated-SPECT n=277 AUC: 0.69±0.03 P=0.018ungated-SPECT n=188 AUC: 0.63±0.04 P=0.023 P=ns vs Gated
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0
0.25
0.5
0.75
1
0 0.25 0.5 0.75 1
1-Specificity
MR-IMPACT II - MVD33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA
Se
ns
itiv
ity
CardioVascularMR Center Zurich
SPECT all n=339 AUC: 0.72±0.03 P=0.003
Perfusion-CMR n=339 AUC: 0.80±0.03
gated-SPECT n=188 AUC: 0.75±0.04 P=0.040ungated-SPECT n=140 AUC: 0.69±0.05 P=0.049 P=ns vs Gated
1-3 VD SPECT
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MR-IMPACT IIIt is the largest multicenter MR/SPECT trial performed so far using 99mTc-tracers and ECG-gating (33 centers, 465 patients)It shows:
Perfusion-CMR (at 0.075 mmol/kg Gd-DTPA- BMA) is superior to SPECT for the detection of coronary artery disease
Perfusion-CMR is a short and safe test, is sensitive and specific, and can be recommended as an alternative for SPECT imaging in experienced centers
CardioVascularMR Center Zurich
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Comparison of 3T vs. 1.5T CMR Comparison of 3T vs. 1.5T CMR PerfusionPerfusion3T Stress3T Stress 1.5T Stress1.5T Stress
• 61 patients (age 64±8 years)61 patients (age 64±8 years)
• Referred for diagnostic CA for Referred for diagnostic CA for investigation ofinvestigation of exertional CP exertional CP
• Stress/rest perfusion CMR at Stress/rest perfusion CMR at both 1.5T both 1.5T (Sonata) (Sonata) and 3T and 3T (Trio) (Trio) on same dayon same day
1.00.80.60.40.20
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0
Se
ns
itiv
ity
3 T AUC: 0.89±0.05
1.5 T AUC: 0.70±0.08
p < 0.05
1.00.80.60.40.20
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0
Se
ns
itiv
ity
3 T AUC: 0.89±0.05
1.5 T AUC: 0.70±0.08
p < 0.05
1.00.80.60.40.20
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0
Se
ns
itiv
ity
3 T AUC: 0.95±0.03
1.5 T AUC: 0.82±0.06
p < 0.05
1.00.80.60.40.20
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0
Se
ns
itiv
ity
3 T AUC: 0.95±0.03
1.5 T AUC: 0.82±0.06
p < 0.05
MVDMVD SVDSVD
3T provided a significant 3T provided a significant increase in SNR (17±6 vs. increase in SNR (17±6 vs. 11±2; p<0.01) compared to 11±2; p<0.01) compared to 1.5T1.5T
Cheng A et al, JACC in pressCheng A et al, JACC in press
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• High resolution anatomy
• Global / regional function
• Regional perfusion
• Viability/Oedema/Fibrosis
• Coronary Angiography
Comprehensive CMR Study
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Delayed Enhancement MRI
• 10 – 20 min post Gd DTPA
• Inversion recovery FLASH or True-FISP
• “Bright is dead”
• Normal, stunned, hibernating
myocardium is dark
Kim R et al, Circulation 1999
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Kim R et al, NEJM 2001
Delayed Enhancement MRI
In vivo infarct imaging
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LV Function: cine MRILV Function: cine MRI Myocardial Viability: Myocardial Viability: DE-MRIDE-MRI
Superior to SPECT for the Superior to SPECT for the detection of sub-endocardial detection of sub-endocardial infarctioninfarctionWagner et al Lancet 361:378Wagner et al Lancet 361:378
Example: Acute Antero-Septal Infarction
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Relationship between transmural extent of HE before bypass Relationship between transmural extent of HE before bypass surgery and likelihood of increased contractility after surgerysurgery and likelihood of increased contractility after surgery
Transmural Extent of Hyperenhancement (%)
Imp
rove
d c
on
trac
tili
ty (
%)
0
20
40
60
80
01-25
26-5051-75
76-100
100
(156
/190
)
(156
/190
)(1
10 /1
72)
(110
/172
)(8
0/16
2)
(80/
162)
(16/
63)
(16/
63)
(1/ 2
5)
(1/ 2
5)
All Dysfunctional Segments
Selvanayagam J et al Selvanayagam J et al Circulation 2004Circulation 2004
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Example: Viable vs. non-viable myocardium
Baseline Cine
Del. Enhancement
6 Months Cine
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Delayed Enhancement Phenomenon
Acute Myocarditis HCM: Fibrosis
Not specific for ischemic injury
M. Friedrich et al S. Petersen et al McCrohon et al Circulation 2003
DCM: Fibrosis
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Imaging of Myocardial Oedema
Aletras et al Circulation 2006
Salvaged myocardium = Area at risk (T2w)– Area of necrosis (DE)
90 min occlusionreperfusionMicrospheres: AARTTC staining: AON
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• High resolution anatomy
• Global / regional function
• Regional perfusion
• Viability/Oedema/Fibrosis
• Coronary Angiography
Comprehensive CMR Study
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MR Coronary Angiography:Fundamental challenges
• Small structures (1-4mm diameter)
• Need 3 D resolution
• Move rapidly with cardiac cycle
and respiration (RCA by ~ 10cm)
Spatial resolution Temporal resolution
Cardiac cath 0.3 x 0.3 mm 8 ms (shutter speed)
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CT Coronary Angiography
Spatial resolution Temporal resolution0.4 x 0.4 x 0.4 mm 120 ms
Achenbach S,Erlangen University
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MR Coronary Angiography
Spatial resolution Temporal resolution0.6 x 0.6 x 0.6 mm minutes (navigator)
Sakuma H,Matsusaka Central Hospital, Mie, Japan
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CMR research in patients undergoing PCI
CMR: New level of understanding of the interrelations amongst coronary stenosis, myocardial blood flow, function and irreversible injury
1. Use of CMR in monitoring injury from revascularisation procedures
2. Blood flow in
hibernating myocardium
With A. Banning, K. Channon, J. Selvanayagam
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Use of CMR in monitoring injury from revascularisation procedures
Questions Occurrence and location of peri-procedural myocardial necrosis in complex PCI?
Relationship between magnitude of troponin rise to the volume of myocardial
tissue loss?
Mechanisms of irreversible myocardial tissue injury?
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New HE-8.5g; Trop I 4.8New HE-8.5g; Trop I 4.8
48 consecutive patients undergoing complex PCI48 consecutive patients undergoing complex PCIall received aspirin, clopidogrel and abciximaball received aspirin, clopidogrel and abciximab
24hr Pre and 24 hr Post PCI MRI; pre and 24 hr troponin I24hr Pre and 24 hr Post PCI MRI; pre and 24 hr troponin I
Selvanayagam JB et al, Circulation 2005Selvanayagam JB et al, Circulation 2005
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Irreversible myocardial injury
New HyperenhancementNew Hyperenhancement• 14/48 14/48 (29%)(29%) patientspatients
4
8
n = 14n = 14 n = 48n = 48
5% of LV 5% of LV MassMass
1.7 % of LV 1.7 % of LV MassMass
New
Hyp
eren
han
cem
ent
(gra
ms)
New
Hyp
eren
han
cem
ent
(gra
ms)
Selvanayagam JB et alSelvanayagam JB et al
Circulation 2005Circulation 2005
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Correlation of cTnI rise with new myocardial hyperenhancement
33
88
1313
1818N
ew H
yper
enh
ance
men
t (g
ram
s)N
ew H
yper
enh
ance
men
t (g
ram
s)
22 55 88
Troponin rise at 24 hrs (Troponin rise at 24 hrs (ųųg/L)g/L)
r= 0.84r= 0.84
p<0.001p<0.001
00
n = 48n = 48
Selvanayagam JB et al, Circulation 2005Selvanayagam JB et al, Circulation 2005
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Relationship Between Plaque Volume and Occurrence and Location of Peri-Procedural Myocardial Necrosis Following PCI
New HENew HE• 15/64 (23%)15/64 (23%) vesselsvessels
2
4
n = 8n = 8 n = 7n = 7New
New
Hyp
eren
han
cem
ent
(gra
ms)
Hyp
eren
han
cem
ent
(gra
ms)
p p = 0.6= 0.6
DistalDistal AdjacentAdjacent
Porto I et al, Circulation 2006 Porto I et al, Circulation 2006
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Example: Pre PCI
AngiogramAngiogram IVUSIVUS DE-CMR DE-CMR
Porto I et al, Circulation 2006 Porto I et al, Circulation 2006
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Example: Post PCI
AngiogramAngiogram IVUSIVUS DE-CMR DE-CMR
Porto I et al, Circulation 2006 Porto I et al, Circulation 2006
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Plaque Volume vs. Location of Peri-Procedural Myocardial Necrosis
}}** }}**}}** }}**
**p<0.001p<0.001
No HENo HE DistalDistal AdjacentAdjacent No HENo HE DistalDistal AdjacentAdjacent
Porto I et al, Circulation 2006 Porto I et al, Circulation 2006
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Blood flow in hibernating myocardium
Impairment in perfusion reserve is well recognized in myocardium supplied by significantly diseased coronary arteries (CAD)
However, it is unknown whether resting blood flow is abnormal in such myocardium
Studies to date mainly using PET have produced conflicting results
Background
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Methods
27 patients undergoing percutaneous coronary intervention (PCI)
one/ two vessel CAD (>85% stenosis by QCA) at least one dysfunctional segment
Cine & Cine & Rest Rest
Perfusion Perfusion DE CMRDE CMR
PCIPCICine Cine
Rest PerfusionRest Perfusion
DE CMRDE CMR
Cine Cine CMRCMR
9 months9 months24h24h 24h24h
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CMR Perfusion: Absolute quantification of blood flow
95% stenosis of proximal LAD95% stenosis of proximal LAD
Selvanayagam JB et al, Circulation 2005Selvanayagam JB et al, Circulation 2005
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Blood flow in hibernating segments
• No delayed enhancement
• Significant recovery of function at 9 months
Selvanayagam JB et al, Circulation 2005Selvanayagam JB et al, Circulation 2005
Segments with
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MeanMeancorrectedcorrected
MBFMBFpre-PCIpre-PCI
** ****
******
p < 0.001p < 0.001p < 0.0001p < 0.0001
NSNS
Selvanayagam JB et al Circulation 2005Selvanayagam JB et al Circulation 2005
Relationship between transmural scar and baseline/post- PCI blood flow
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• Troponin elevation 24 hr post PCI represents new Troponin elevation 24 hr post PCI represents new myocardial injurymyocardial injury
• Both impairment of side branches and distal embolisation of Both impairment of side branches and distal embolisation of plaque material contribute to myocardial necrosis during PCIplaque material contribute to myocardial necrosis during PCI
• Resting myocardial blood flow is reduced in hibernating Resting myocardial blood flow is reduced in hibernating myocardiummyocardium
Summary of Oxford PCI research studies
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Clinical CMR Techniques on the Horizon• Regional strain (tissue phase mapping)
• Non-contrast perfusion (ASL)
• Oxygenation (BOLD)
• 23Na-Imaging
• Metabolism (MRS)
• 7 Tesla
• Molecular ImagingSelvanayagam J et al, works in progress
Robson M et al Works in Progress
PCr
- - -ATP
2,3-DPG
PDE
5 0 -5 -10 -15 -20 ppm
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Non-invasiveimaging tool
MRI in Ischemic Heart Disease
Multi-parametricphenotyping
Clinical studies of patients with IHD
DiagnosticCardiology
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Acknowledgments
OCMRJoseph Selvanayagam, Ranjit Arnold, Adrian Cheng
CollaboratorsAdrian Banning
Keith Channon
Michael Jerosch-Herold
Italo Porto
William van Gaal
FundingBritish Heart FoundationMedical Research CouncilThe Wellcome TrustSiemens Medical Solutions
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Myocardial Viability: Clinical Relevance
Schelbert H et al,Seminars in Nuclear Medicine 2002
Pagano et al, J Thorac Cardiovasc Surgery 1998
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Myocardial ViabilityThe Clinical Problem:
Akinetic myocardium,supplied by stenosed coronary artery
Viable= Stunning, Hibernation
Non-viable= Scar
Revascularisation(PTCA, CABG)
No Revascularisation
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Methods The diagnostic coronary angiogram was used to define affected
myocardial segments
Wall motion was assessed visually:normal 1; hypokinetic 2; akinetic 3; dyskinetic 4.
In each slice, MBF was determined for 8 myocardial sectors in ml/min/g by deconvolution of signal intensity curves with an arterial input function measured in the LV blood pool
Jerosch-Herold, M. et. al JMRI 2004
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ResultsCoronary lesion severity was 80-95% stenosis by quantitative coronary angiography
Mean MBF normalized by rate pressure product (‘corrected MBF’) was 1.2+/-0.3 in segments without significant coronary stenosis and 0.7 +/-0.2 in segments with coronary stenosis pre PCI (z=23.9, p<0.001)
Early post procedure, the MBF was 1.2+/-0.2 in revascularised segments, and 1.3+/-0.2 in non-diseased segments
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Methods
Prep
3 MinAdeno
0.14mg//kg/min
LEImaging
BH BH
25‘
MR Study and Monitoring:
CardioVascularMR Center Zurich
–2 to 0hVit Signs
12-ECG
1-1.5 hVit S
12-ECG
24 hVit SPhys
12-ECGLabAE
1 hVit S
12-ECG
- 36h to 0 hHistory
Phys. ExamSymptomsPreg TestBlood Lab
4 weeks: QCA
4 weeks: SPECT
4 weeks: QCA
4 weeks: SPECT
0.075 mmol/kg Gd-DTPA-BMA
0.075 mmol/kg Gd-DTPA-BMA
Vital signs (HR, BP, O2 sat, etc)
~1.5h
72 hAE10‘
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SPECT stress perfusion
99mTc: Sestamibi, Teboroxime, Tetrofosmin
SPECT Study: gated-SPECT (ungated-SPECT allowed if clinical routine)
Multi-Vendor1-Day Protocol permitted
Preparation
Adeno 0.14mg/ /kg/min
Stress Rest
CardioVascularMR Center Zurich
Methods
Identical to stress perfusion
99mTc: Sestamibi, Teboroxime, Tetrofosmin
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• Physics complex
• Nuclear spin
• External magnetic field
• RF waves -> FID
MR (NMR) - Nuclear Magnetic ResonanceMR (NMR) - Nuclear Magnetic Resonance
• Magnetic field gradient
• MR image contrast: - Spin density
- Relaxation (T1, T2)
- Flow
- Pulse sequence
Nature 1973; 242:190-191