recent advances in quantitative mr spectroscopy · recent advances in quantitative mr spectroscopy...
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July 2009
Recent advances in quantitative MR spectroscopy
Anke Henning, PhDInstitute for Biomedical Engineering, University and ETH Zurich, Switzerland
AAPM 2009 – Quantitative MRI and MRS Symposium
Cho tCr
Ins
tCr
GlxGlx
NAA
Gln
NAA
3T
Courtesy: Dept. of Radiology, University of Bonn, GermanyCourtesy: Dept. of Radiology, University of Bonn, Germany
MOTIVATION: non-invasive metabolite quantification
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AAPM 2009 – Quantitative MRI and MRS Symposium
NAA
CreCho
MOTIVATION: Spectroscopic Imaging
NAA
Cho
AAPM 2009 – Quantitative MRI and MRS Symposium
B0
f0 = γ* x B0
γ: property of nucleus
γ*H = 42.58 Mhz/T
γ*P = 17.24 Mhz/T
γ*C = 10.71 Mhz/T
)2πγ
*(γ =
51.7 MHz25.85 MHz31P
127.73 MHz63.86 MHz1H
3 T1.5 T
Lamor frequency
13C 32.12 MHz16.06 MHz
BASIC PRINCIPLE: Larmor frequency
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AAPM 2009 – Quantitative MRI and MRS Symposium
+H
-e
B0
BASIC PRINCIPLE: Chemical Shift
AAPM 2009 – Quantitative MRI and MRS Symposium
H HC
H
ion bondinghydrogen deprived from electron
weak shielding
covalent bondingshared electrons
strong shielding
Water Water FatFat
BASIC PRINCIPLE: Chemical Shift
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AAPM 2009 – Quantitative MRI and MRS Symposium
Cho
Cre
NAA
t
FID
Spectrum
f
Cho CreNAA
FTTime domain Frequency domain
BASIC PRINCIPLE: Chemical Shift
AAPM 2009 – Quantitative MRI and MRS Symposium
BASIC PRINCIPLE: J-coupling
O H
C-C-CH3
O OHrest CH CH3
OH
1:1
1:3:3:1
1H SPECTRUM OF LACTATE
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AAPM 2009 – Quantitative MRI and MRS Symposium
BASIC PRINCIPLE: metabolite concentrations
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION
area under peak / amplitue of FID
estimation of fitting reliability
additional influence factors
reference standard
concentrations in mM
relat
iveab
solu
te
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION
Estimation of area under peak / amplitue of FID: - time domain vs. frequency domain- peak integration- line fitting (JMRUI/AMARES; scanner packages)
- fitting of basis spectra (LC Model; JMRUI/QUEST; TDFD Fit )
- considering phase evolution & distortion- considering RF pulses- spatial statistics for MRSI fitting- 2D prior knowledge fitting (ProFit)
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: time vs. frequency domain
jMRUIVAPRO
SVD
TDFDfitLCmodel
ProFit
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: time vs. frequency domaintime domain fitting frequency domain fitting
TDFDfit: Slotboom et al; Magn Reson Med. 1998 Jun;39(6):899-911.
signal truncationcan be considered
frequency range can not berestricted residual waterand lipid signals have to bemodeled or suppressed byadditional filters
fitting of multi-frequencybasis spectra is not straight forward
user-dependent prior knowledgerequired to initialise fit: frequencies, linewidth, phase
signal truncationcan not be considered directly
frequency range can berestricted residual waterand lipid might be consideredas baseline
fitting of linear combination of multi-frequency basis spectrastraight forward
no user-dependent priorknowledge required to initialisefit
discrete time domain model and frequency domain fitting
AAPM 2009 – Quantitative MRI and MRS Symposium
Problemsoverlapping peaksbaselinephasing
-> magnitude spectra-> complex integration
depends on shimming
QUANTIFICATION: peak integration
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: peak fitting
Problemsoverlapping peaks baselinephasing
-> magnitude spectra-> complex integration
depends on shimming
JMRUI/AMARES; scanner packages
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: Fitting basis spectraFitting a linear combination of basis spectra
LCmodel; TDFDfit; ProFit; jMRUI/QUEST
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: macro-molecular baseline
De Graaf; In vivo NMR spectroscopy; WILEY 2007 (2nd Edition)
Hofmann L et al, Magn Reson Med.2002 Sep;48(3):440-53.
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: “spline fit” (LCModel)
insufficient water suppression
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AAPM 2009 – Quantitative MRI and MRS Symposium
RF
GR
90°5.5 ms
Cre
Cho
Glx
NAA
MM
strong linear phaseacquisition delay
= truncation of first
few points of the FID
FID(LOVS) MRSI
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
QUANTIFICATION: truncation of FID
AAPM 2009 – Quantitative MRI and MRS Symposium
OVSOVSOVS
RF
GM
GP
GS
VAPOR - WS MRSI
90° * 90° 160° 90° 140° 90° 160° 160°
150 ms 100 ms 122 ms 105 ms 102 ms 61 ms 67 ms **
FID acquisition Localized by Outer Volume Supression
Tkac et al, Magn Reson Med, 41:649-659, 1999. Henning et al, Magn Reson Med 59:40-51, 2008.
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
QUANTIFICATION: truncation of FID
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AAPM 2009 – Quantitative MRI and MRS Symposium
NAA
a ba
b
c
NAA
Cre
Cho
modulationsidebands
two pulse WS prior OVS VAPOR
QUANTIFICATION: truncation of FID
AAPM 2009 – Quantitative MRI and MRS Symposium
Non-apodized spectra from individual voxels
white matter
Voxel size: 1 ml; TR = 4500 ms; Acquisition time: 26 min
AspGln
NAAG
Glu
Cho
Tau
mI
GlxCre
scylloI
CreGM
Cre
NAA
NAAG
GSHCho
GABA
NAA
Cre Glx mI
NAA
WM
grey matter
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
How reliable is the quantification of FIDLOVS MRSI data?
QUANTIFICATION: truncation of FID
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AAPM 2009 – Quantitative MRI and MRS Symposium
NAA
Cre
Cho
mI
GSH
GABA
Glu
Gln
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
QUANTIFICATION: truncation of FID
truncationincorporated
in the time domainof model spectra
AAPM 2009 – Quantitative MRI and MRS SymposiumHenning et al, NMR in Biomedicine (Epub ahead of print), 2009.
QUANTIFICATION: truncation of FID
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AAPM 2009 – Quantitative MRI and MRS Symposium
voxel size: 1 ml
(1 cm3)
no phase correction prior fitting
phase correction prior fitting
QUANTIFICATION: truncation of FID
AAPM 2009 – Quantitative MRI and MRS Symposium
90° 180°t2
Tacq=TE=t1(1)
QUANTIFICATION: 2D J-resolved MRS
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AAPM 2009 – Quantitative MRI and MRS Symposium
90° 180°t2
Tacq=TE=t1(2)
QUANTIFICATION: 2D J-resolved MRS
AAPM 2009 – Quantitative MRI and MRS Symposium
90° 180°t2
Tacq=TE=t1(3)
QUANTIFICATION: 2D J-resolved MRS
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AAPM 2009 – Quantitative MRI and MRS Symposium
90° 180°
CSsame evolution
FT along t1
Jdifferent evolution
QUANTIFICATION: 2D J-resolved MRS
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: 2D JPRESS & ProFIT
Schulte et al, NMR Biomed 19(2), 255-263 & 264-270, 2006.
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: 2D JPRESS & ProFIT
Schulte et al, NMR Biomed 19(2), 255-263 & 264-270, 2006.
time efficient
model-free regularization
fit of linear combination of model spectra(discrete, simulated time domain model:
max echo sampling pattern considered)
global fit parameters: zeroth-order phaseGaussian line broadening in f2shift in f1biexponential phase decay due
to eddy currents
individual fit parameters: concentrationsame exponential line-broadening
for f1 and f2shift in f2
robust convergence
ProFit = VAPRO & LCModel
AAPM 2009 – Quantitative MRI and MRS Symposium
fitting a linear combinationof 2-dimensional COSY basis metabolite sets
Alexander Fuchs, IBT
QUANTIFICATION: COSY & ProFIT
Extension of ProFitto other 1D or 2D sequences possible!
courte
sy of IBT, Unive
rsity a
nd ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION
Estimation of fitting reliability:- Residue- Cramer-Rao lower bounds (CRLB) - Covariance matrix- CRLB maps for MRSI
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: residue
Tkac I et al; ISMRM (2008) 16:1624 Govindaraju et al; ………………..
mouse brain, 9.4 T
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: Fisher information matrix
De Graaf; In vivo NMR spectroscopy; WILEY 2007 (2nd Edition)
)(1
2 DPDPF HT
Nσ=
Fisher information matrix
standard deviation of noise
transposition
Hermitianconjugation
j
iij p
xD
∂∂
=
model function matrix element:
model function
parameter n
mmn p
pP
∂∂
=
prior knowledge matrix element:
parameter n
parameter m
model function: exponentially damped, gaussian filtered sinusoidsparameters: metabolite prior knowledge (frequencies, coupling constants)
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: CRLB1−=≥ iipp FCRLB
iiσ inverted Fisher
information matrix
Cramer-Rao Lower bounds
standard deviationof fitting result for
parameter i
Tkac I et al; ISMRM (2008) 16:1624.
diagonal elements
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AAPM 2009 – Quantitative MRI and MRS Symposium
Ala
Asc
Asp Glc
LacCre
GA
BA
Gln
Glu
tCh
o
GS
H mI
MM
/ L
ip
NA
A
NA
AG
PE
scyl
loI
Tau
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
1H FIDLOVS MRSI @ 7T
statistical analysis considers SNR
QUANTIFICATION: CRLB
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: covariance matrix
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1
−−
−
=nnmm
mnmn
FF
Fρ
unambiguous and simultaneous quantification of GABA, Gln, Glu and NAA
JPRESS @ 3T
Walter/Henning/Grimm et al, Archives of General Psychiatry 2009; 66(5):478-486
covariance coefficientfor parameters m and n inverted Fisher
information matrices
off-diagonal elements
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: covariance matrix
JPRESSCOSY
1D
Fuchs et al, ISMRM (2009) 17: 2406.
3T
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
GM WM
GM WM Cortex voxel
GM
WM Cor
voxel size: 0.2 ml (6 mm3)
QUANTIFICATION: covariance matrix & CRLB maps1H FIDLOVS MRSI @ 7T
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
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AAPM 2009 – Quantitative MRI and MRS Symposium
no phase correction prior fittingTau
scylloIPE
PChNAAGNAA
MM/LipmI
LacGSHGPCGluGlnGlc
GABACreAspAscAla
Ala
Asc
Asp Cre
GA
BA
Glc
Gln
Glu
GP
CG
SH
Lac m
IM
M/ L
ipN
AA
NA
AG
PC
hP
Esc
yllo
IT
au Ala
Asc
Asp Cre
GA
BA
Glc
Gln
Glu
GP
CG
SH
Lac m
IM
M/ L
ipN
AA
NA
AG
PC
hP
Esc
yllo
IT
au
phase correction prior fitting
correlation analysis considers spectral overlap at original shim quality
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
QUANTIFICATION: covariance matrix1H FIDLOVS MRSI @ 7T
AAPM 2009 – Quantitative MRI and MRS Symposium
no phase correction prior fitting
QUANTIFICATION: CRLB maps
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
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AAPM 2009 – Quantitative MRI and MRS Symposium
phase correction prior fitting
QUANTIFICATION: CRLB maps
Henning et al, NMR in Biomedicine (Epub ahead of print), 2009.
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATIONAdditional influence factors:
Smet = Cmet x NS x RG x V x ω0 x fsequence x fcoil x fadd
# averages receive gain
volume
volume
metaboliteconcentration
metabolitesignal
intensity
fsequence:
fcoil:
fadd:
TE (T2); TR (T1); partial volume effectsRF pulses (phase evolution, NOE);gradients (diffusion)
transmit and receive B1 distribution, power optimizationcoil load (load dependent resistance of coil)contributing nuclei per moleculeB0 , temperature, pH, conductivity artifacts (f.i. eddy currents; lipid and water)
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AAPM 2009 – Quantitative MRI and MRS Symposium
Relaxation
Tkac et al; Magn Reson Med 46:451, 2001
T2 relaxation
invivoE
phantomET TT
TTf
)/exp(
)/exp(
2
2
2 −−
=
invivoR
phantomRT TT
TTf
)/exp(1
)/exp(1
1
1
1 −−−−
=
1T2T
metcorr,met f*f
cc =
Or: TR > 5 T1, max
TE ultra-short (also for diffusion)
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: IDAP
IDAP: Kreis et al, Magn Reson Med 54, 761-768, 2005; .TDFDfit:
multi-dimensional fitting
Slotboom et al; Magn Reson Med. 1998 Jun;39(6):899-911.
Basis spectra can be subdived intoparts with different T2 relaxation behavior:T2 determination from lineshape analysis.
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AAPM 2009 – Quantitative MRI and MRS Symposium
0.5 kHz
0.9 kHz
1.6 kHz90°
180°
180°
1.6 kHz
3.6 kHz
28.3 kHz9.1 kHz4.65 kHz
90°
180°
30°90°150°
RF pulses
AAPM 2009 – Quantitative MRI and MRS Symposium
LacGlxH2O NAACre
0 -1000-200 -400 -600 -800
90° 180°90° 180°
excitation & refocusing
RF pulses
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AAPM 2009 – Quantitative MRI and MRS Symposium
RF pulses
90° 180°
90°
180°
PRESS7T
brain phantomTE = 66 ms
pulses andgradients need
to be consideredin simulations
of basis spectra
AAPM 2009 – Quantitative MRI and MRS Symposium
Contributing nuclei per molecule
CH3
HO-CH2-CH2-N-CH3
CH3
CholineO O
C-CH2-CH-C
O NH O
C=O
CH3
N-Acetylaspartate
H3C-N-CH2-COO-
C=NH2+
NH2
Creatine
2 mM 6 mM
12 mM
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AAPM 2009 – Quantitative MRI and MRS Symposium
B1 and B0 inhomogeneity
De Graaf; In vivo NMR spectroscopy; WILEY 2007 (2nd Edition)
Transmit B1
B0
line broadephase encod
AAPM 2009 – Quantitative MRI and MRS Symposium
Conductivity, pH and temperature
0))()(3
21()( BTTTwater σχγω −−=
Buchli R.; SMRM (1990) 9:504
De Graaf; In vivo NMR spectroscopy; WILEY 2007 (2nd Edition)
bulk susceptibility electronicshielding
)log(δδ
δδ−
−+=A
HAApKpH
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION
Reference standards:-Internal reference standards (water, creatine)
-External reference calibration (simultaneous phantom calibration)
-Symmetric phantom calibration-Phantom replacement method (simulation phantom calibration)
-ERETIC (Electric reference to assess in vivo concentrations)
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: metabolite ratios
tCr (PCr + Cr): 1. Energy Buffer:H + PCr + ADP ⇔ ATP + Cr
2. Energy shuttle: “Energy transport” from production (mitochondria) to energy utilizing sites
The CRE peak is stable during activation/exercise and therefore may serve as an internal reference for 1H MRS.
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: metabolite ratios
relative quantification: ambigious
or ?
healthy pathology
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: internal water reference
assumes stable and known water concentration
additional unsuppressed water spectrum needs to be measured from same voxel
be sure the same preparation settings are used (e.g. receiver gain & power optimizations, shimming)
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: internal referencesAdvantages Disadvantages
coil loadreceive gain settingsvolumetemperaturpHconductivity
are considered
B1 inhomogeneities power optimization
are considered forthe same type of nucleus (f.i. internalwater reference for 1H MRS)
internal water or referencemetabolite concentrations as well as all relaxation times depend on:
agevoxel composition (f.i. CSF content)
and change in pathologies
B1 inhomogeneities PO
are not considered fordifferent types of nuclei(f.i. internal water referencefor 31P and 13C MRS)
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: external reference calibration
External reference calibrationphantom with known concentrationB1 variations should be taken into account especiallyfor surface coilsbe sure the same preparation settings are used
(f.i. receiver gain & power optimizations, shimming)
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: external reference calibrationAdvantages Disadvantages
additional reference spectrumneeded each timereceive gain settingsvolumetemperaturpHconductivityB1 inhomogeneitiespower optimizationrelaxation times of in vivo metabolites
need to be consideredby adjustments or correctionfactors determined byadditional measurements
known & stableconcentration forreference standard
known relaxation timesfor reference standard
coil load is directlyconsidered
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: symmetrical phantom calibration
Symmetric phantom calibrationphantom with known concentrationbe sure the same preparation settings are used for localized version(f.i. receiver gain & power optimizations, shimming)
Buchli et al, MRM (1993) 30: 552-558.
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: symmetrical phantom calibrationAdvantages Disadvantages
additional reference spectrumneeded each timereceive gainvolumetemperaturpHconductivityrelaxation times of in vivo metabolites
need to be consideredby adjustments or correctionfactors determined byadditional measurements
known & stableconcentration forreference standard
known relaxation timesfor reference standard
coil load is directlyconsideredB1 inhomogeneities aredirectly considered ifconductivity of phantom isadjusted to in vivo valuesand PO is not repeated forphantom measurement
AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: phantom replacement method
make sure to adjust coil load to in-vivo condition by moving the saline tube in or out each time
correction for receiver gain is necessary
power optimization & shim differences are not considered
saline
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: phantom calibration methodsAdvantages Disadvantages
coil load (additional reference spectrumneeded each time)receive gain settingsvolumetemperaturpHconductivityB1 inhomogeneities PO relaxation times of in vivo metabolites
need to be consideredby adjustments or correctionfactors determined byadditional measurements
known & stableconcentration forreference standardknown relaxation timesfor reference standard
AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: Electric REference To access In vivo Concentrations
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: Fitting with LC Model & TDFD fit
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: Electric REference To access In vivo Concentrations
Why ERETIC?
1H MRS @ 1.5T and 3T: reliable reference standard in lesions where waterconcentration is unknown
clinical application
13C & 31P MRS @ 3T & 7T: reliable reference standard
no internal reference availablewater reference is unreliable sincetransmit and receive fields of waterand heavy nucleus are very different at 3T & 7T
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AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: optical signal transmission
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: optical vs. electrical signal transmission
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: scaling with coil load
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: stability over time
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: phantom calibration
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
ERETIC: cross validation with internal water reference
Heinzer-Schweizer et al, ISMRM 2009: 232
courtesy of IBT, University and ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
31P MRS: simultaneous 1H decoupling and ERETIC
Schweizer et al, ISMRM 2008: 193.
ATP ATP
courtesy of IBT, University and ETH Zurich
AAPM 2009 – Quantitative MRI and MRS Symposium
JPRESS & ERETIC
ERETIC NAA Cho Cr Cr
in vivo, 3T, GM rich voxel
H2OMM
Fuchs et al, ISMRM 2009: 2405.
courtesy of IBT, University and ETH Zurich
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AAPM 2009 – Quantitative MRI and MRS Symposium
QUANTIFICATION: ERETICAdvantages Disadvantages
volumetemperaturpHconductivityB1 inhomogeneities PO relaxation times of in vivo metabolites
need to be considereddue to adjustments orcorrection factorsdetermined byadditional measurements
known & stablereference standardknown relaxation timesfor calibration metabolitesreceive gain settingsconsideredcoil load directlyconsideredphantom calibration needsto be performed only once
AAPM 2009 – Quantitative MRI and MRS Symposium
IBT spectroscopy group
Mateo PavanNicola de Zanches Rolf F. SchulteKlaas Pruessmann