Novel MRI based Approaches to Study Human Body

Novel MRI based Approaches to
Study Human Body
Uzay E Emir
Center for Magnetic Resonance Research
University of Minnesota
Minneapolis, Minnesota, USA

Declaration of Relevant
Financial Interests or Relationships
Speaker Name: Uzay E Emir
I have no relevant financial interest or relationship to disclose with regard to the
subject matter of this presentation.
ISMRM
20th ANNUAL MEETING & EXHIBITION
“Adapting MR in a Changing World”

Comparative History
• Comparative history is the comparison of
different societies which existed during the
same time period.
– Automobile Society
– Smartphone Society
– 1H MRS @high field

Automobile Society
• 2001
…
• 2012

Smartphone Society
• 2001
…
• 2012

2001
NAA
Glu
Asp
NAA
Gln
Cr
PCr
Ins
Tau
Cr
PCr
Gln
Glu
Ins
H2O
Glc
NT = 64
STEAM
TE = 6 ms TR = 5 s
VOI = 2 x 2 x 2 cm3
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 ppm
5.0
5.5
6.0
Tkáč, MRM,2001

Potentials
Tkáč, MRM,2009
1
2
3
4
5
6 ppm
6
x 5
NT = 128
S/N = 130
1
2
3
4
5 ppm
Glc
x 5
NT = 128
S/N = 264
• Increase in signal-to-noise-
ratio (SNR)
• Increase in chemical shift
dispersion

Potentials
• Increase in signal-to-noise-
ratio (SNR)
• Increase in chemical shift
dispersion
• Reliable quantification of
up to 17 metabolites
Glu
4T
7T
Gln
4T
7T
2 4 8 16 32 64 128
NT
0.0
0.2
0.4
0.6
0.8
1.0
CRLB
(µmol/g)
2 4 8 16 32 64 128
NT
0.0
0.3
0.6
0.9
1.2
1.5
CRLB
(µmol/g)
The precision at 4T
for NT 128
corresponds to the
precision at 7T for
NT 4.
Tkáč, MRM,2009

• Non-uniform B1 field
• B1 (max) transmit field > 24 μT
– long RF pulses (Chemical Shift
Displacement Error)
• Limits of specific absorption rate
(SAR)
• Increased hardware requirements
– B0 gradients
– RF coils
– Shim coils/currents
• Short T2 relaxation times of
metabolites in the human brain
(Deelchand, JMR,2010)
Challenges
0 2 4 6 8 10
0
100
200
300
400
500
Field Strength (T)
NAA
Cr
T
2
(ms)

Puzzle
Tkáč, MRM, 2001
Garwood, JMR,2001
Scheenen, MAGMA, 2008,
Avdievich, MRM, 2009
Boer, NMR Biomed, 2011
Emir, NMR Biomed, 2012
Marjanska, NMR Biomed, 2012
Boer, NMR Biomed, 2011

Requirements for in vivo MRS
MRS
Hardware
• Transceiver
Coil
• B1 shimming
• B0 shimming
Optimized Pulse
Sequence
• Localization
• Water Suppression
Data
Acquisition
Processing

Spectral Quality
flat baseline
efficient
water suppression
SNR
localization performance
(no lipid contamination)
spectral resolution
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 ppm
5.0
5.5
6.0

Transceiver Coils and B1 shimming
Transmit Receive
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0

Local B1
+ Shimming (Single Voxel
Spectroscopy)
1.3±0.1
Pons
2.6±0.3
Cerebellar Vermis
1.2±0.1
Substantia Nigra
1.6±0.2
Putamen
1.7±0.2
Frontal White
Matter
1.4±0.4
Posterior
Cingulate
Relative Transmit
Efficiency
2.5±0.2
Occipital Cortex
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Preshim Postshim
Postshim
Preshim

B1
+ Shimming (MRSI)
Hetherington, MRM, 2010

B0 Shimming
• Magnetic field distortions:
– non-linear
– scaled with magnetic field
• NOT POSSIBLE TO
COMPENSATE WITH
LINEAR SHIM COILS
– Higher order shims are
required
• 1st and 2nd order shims for SVS
(FASTMAP )
• 3rd and 4th orders shims MRSI
• Good Shimming
– Easier water suppression
– Increased resolution (the
ability to identify and separate
overlapping peak)
– Increased SNR

B0 Shimming
STEAM TE = 8 ms,
VOI = 8ml
Occipital Cortex
FWHM = 20.3 Hz
FWHM = 11.2 Hz
X, Y, Z
XY, XZ, YZ, Z2, X2Y2
X, Y, Z
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 ppm
5.0
5.5
6.0

B0 Shimming (SVS )
Volume
of Interest
Linewidth
[Hz]
Posterior Cingulate 11.3±0.7
Occipital Cortex 12.7±0.3
Cerebellum 14.5±0.6
Pons 14.3±1.9
Frontal White Matter 15.9±0.8
Putamen 15.9±1.2
Substantia Nigra 18±1

Very High Order and Degree B0
Shimming for MRSI @7T
Pan, MRM,2011

Optimized pulse sequence
Water
Suppression
- VAPOR, 7 - 8 RF
pulses
Outer Volume
Suppression
(OVS)
- HS broadband
pulses
-OVS1, OVS2,
OVS3, …
Localization
- STEAM
- SEMI-LASER
- LASER
ACQ

Short echo-time STEAM pulse sequence
Tkáč, Appl. Magn. Reson,2005

Short echo-time SEMI-LASER
Oz, MRM, 2011

OVS
x 10 x 10
without OVS with OVS
-30 0 30
-60 mm -30 0 30
-60 mm
5 4 3 2 1 ppm 5 4 3 2 1 ppm

Water Suppresion
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 ppm
5.0
5.5
6.0
STEAM TE = 8 ms,
VOI = 8ml
Occipital Cortex

Fine Adjustment of Gradient spoiling
(k-space analysis of unwanted signals)
Gz Gz Gz Gz Gz
k-space

Reconstruction of 1H NMR Spectrum From
Multi Channel Coil
Multi Channel Receive Coil
Water
Spectrum
Water Suppressed
Spectrum
Phase and Eddy Current Correction
Weighted Summation
Weighting Factors
Natt, MRM, 2005

Phase and Eddy Current Correction
Occipital cortex
Water suppressed
spectrum
Water spectrum
Phase and Eddy
current corrected spectrum

Weighted Summation
Occipital Cortex Substantia Nigra
Weighting Factor

MRSI @ 7T
Hetherington, MRM,2010
TE=15 ms

MRSI @ 7T
Boer, MRM,2011
TE=2.75 ms

LCModel
4.0 3.5 3.0 2.5 2.0 1.5 1.0 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
MAC
GABA
Glc
Gln
Glu
GSH
Ins
Lac
NAA
NAAG
PE
Scyllo
Tau
Baseline
Asc
Asp
STEAM
TE = 8 ms TR = 5 s
VOI = 8 ml NT = 128
# of subject = 1
Measurement
Fit
Residual

Neurochemical Profiles @ 7T
CRLB ≤ 50%. p < 0.05, ** p < 0.005. Error bars: SD Emir, NMR Biomed, 2012

Summary
• Multiple brain regions-of-interest to study
several neurological diseases
– Multi channel coil
– B1 Shimming
• Reliable quantification of metabolites
• Increased SNR
• Implemented on a clinical consoles

Recipe for MRS @ 7T
routine clinical use
Automatic B0 shimming
Manual RF power adjustment
B1
+ shimming
Highly efficient water suppression (VAPOR)
spectroscopic acquisition

SPINOCEREBELLAR ATAXIAS (SCAs)
Emir, ISMRM, 2012, p1802
Control SCA1
PONS
Cerebellar
Hemispheres
Vermis
Healthy Control SCA1 Presym

Parkinson’s Disease
STEAM + VAPOR + OVS (TE = 8 ms,
TR = 5 s)
VOI: 4.5 mL in pons, 1.7mL in putamen,
1 mL in SN
Emir, PlosOne, 2012

MRSI Tumor
Avdievich, MRM, 2009

Recipe for MRS @ 3T
routine clinical use
Automatic shimming
Automatic RF power adjustment
Highly efficient water suppression (VAPOR)
Spectroscopic acquisition

SPINOCEREBELLAR ATAXIAS
(SCAs)
@3T @7T
PONS
Cerebellar
Hemispheres
Vermis
PONS
Cerebellar
Hemispheres
Vermis
SEMI-LASER
TE=28 ms
TR=5ms
SEMI-LASER
TE=26 ms
TR=5ms

3T vs. 7T
Correlation between
metabolite concentrations
(Glu, Gln, myo-Ins,
NAA+NAAG,
GPC+PCho, Cr+PCr,
Glc+Tau) of individual
subjects determined from
3T and 7T spectra.
# dots ~ (13 patients+15
controls) x 3 brain regions
x 7 metabolites
R2 > 0.8, p <0.0001

MRS @ 3T
1.0
2.0
3.0
4.0 ppm
5.0
6.0
1.0
2.0
3.0
4.0 ppm
5.0
6.0
1.0
2.0
3.0
4.0 ppm
5.0
6.0
CMRR,
SEMI-
LASER
TE=28 ms
TR=5ms
VOI=6.25 ml
MGH,
SEMI-
LASER
TE=28 ms
TR=5ms
VOI=6.25 ml
UPMC, Paris
SEMI-
LASER
TE=28 ms
TR=5ms
VOI=6.25 ml

SEMI-LASER TE=28 ms
TR=5ms VOI 10x10x11 mm3
The Royal Children's Hospital
Caudate

SEMI-LASER TE=28 ms
TR=5ms VOI 11x15x11 mm3
The Royal Children's Hospital
Putamen

Comparative History
• 2001
…
• 2012

Future Remarks
• Current trends suggest
that multimodal imaging
approaches are likely to
be more fruitful than a
single tool.
A representative fusion image set of the brainstem area from a single subject
obtained by positron emission tomography–magnetic resonance imaging
(PET–MRI). F]Fluorodeoxyglucose (18F-FDG)-PET image obtained by high-
resolution research tomograph (HRRT-PET). Son, Neuroimage,2012

Acknowledgements
• Gülin Öz
• Ivan Tkáč
• Melissa Terpstra
• Małgorzata Marjańska
• Pierre-Francois Van De
Moortele
• Eddie Auerbach
• Gregor Adriany
Funding:
• WM KECK Foundation
• R01 EB008645
• P41 RR008079
• P30 NS057091
• NIBIB-EB006835
• R21 EB009133

SPINOCEREBELLAR ATAXIAS (SCAs)
Cerebellar Hemisphere PONS
[myo-Ins] (μmol/g)
[tNAA]
(μmol/g)
[myo-Ins] (μmol/g)
[tNAA]
(μmol/g)
Healthy Control SCA1 Presym

Changes in brain glutathione concentrations after
a single dose of Nacetylcysteine
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
-60 -40 -20 0 20 40 60 80 100 120 140
Time (minutes)
Brain GSH response to NAC
GSH
concentration
(mM)

Novel MRI based Approaches to Study Human Body

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