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Jan Ruff MR Spectroscopy


MREA-MRS

Jan. 2004
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Content

 Why to use MR spectroscopy


 Basics
 What is a spectrum
 Spin-spin coupling
 Water suppression
 Acquisition Techniques
 FID
 SVS
 CSI
 1H MRS Applications
 Head
 Prostate
 Breast
 Tim and Spectroscopy
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Why to use MR spectroscopy?

Spectra contain information from tissue metabolites,


hence they …

 … reflect metabolic states of various tissues

 … show metabolic changes resulting from disease

 … allow to monitor the effect of therapy

 … allow to follow metabolic pathways


in biochemical research
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What is a spectrum?

 The resonance frequency of nuclei is proportional to their local


magnetic field

 =  Beff =  B0 (1-)
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What is a spectrum?
 The local magnetic field depends on the chemical environment of
the proton

Beff = B0 (1-)

B0 applied B0 effective
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What is a spectrum?
 Nuclei of different molecular groups “see” different
local magnetic fields
O
||
C6H5 – CH2 – O – C – CH3 Benzylacetate

H
H |
| –C–H
–C– |
| H
H

/ppm
8 4 0
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J-Coupling (Spin-spin coupling)


Ethylformiat

 interaction of nuclei with nuclear magnetic spin ...


… mediated via adjacent electrons ...
… leads to line splitting into multiplets in n+1 lines ...
… which are independent of magnetic field strength
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Linewidth

 The resonance linewidth is limited due to spin-spin relaxation

1/2 = 1/( T2*)


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About the Concentrations


 In vivo concentration of metabolites of interest: ~ 10 mMol/l

 1H conc. in water : 2 x 55.6 Mol/l

 Sig.Int. (metabolites)
~1/10000 Sig.Int. (H2O)
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Water Suppression
 Chemical Shift selective suppression (Chess)
 realized as WET (water supprssion enhanced through T1 effects)
with three frequ. sel. (~35 Hz) saturation pulses with optimized flip
angles
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Acquisition techniques

 FID
selection of the entire part of the object
“seen” by the coil

 SVS: Single Voxel Spectroscopy


selection of a volume of interest (VoI)
by slice selective pulses

 CSI: Chemical Shift Imaging


spatial encoding over a VoI by
phase encoding
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FID

90° data acquisition


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FID

90° data acquisition

0.35ms

 Pulse – acquire
 selection of the entire part of the object
“seen” by the coil
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FID

90° data acquisition

G phase

G read

G slice

spoiler
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SVS: Overview

Advantages (vs. CSI methods)


 simplicity
 low minimal scan times
 precise VoI definition
 allows accurate localized shimming

Disadvantages
 time consuming in the case of multivoxel applications
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SVS: Voxel Selection


exc.
RF

Gy

refoc. refoc.
RF RF

Gx Gz
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SVS – Spin Echo

90° 180° 180° data acquisition

TE1/2 TE1/2 - TE2/2 TE2/2

G read

G phase

G slice
spoiler

 90º -- TE1/2 -- 180º -- TE1/2 -- TE2/2 -- 180º -- TE2/2 -- AQC

 Asymmetric echo timing


 Theoretical treatment as a spin echo sequence, with only one 180 º pulse; the coupling effect
only influences the period after the second refocusing.
 Self-refocussing 180º pulses
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SVS – STimulated-Echo Acquisition Mode

90° 90° 90° data acquisition

TE/2 TM TE/2

G read

G phase

G slice
spoiler

 90º -- TE/2 -- 90º -- TM/2 -- 90º -- TE/2 -- AQC.

 TE/2 = time between 1st and 2nd pulse.

 TM : magnetization is saved in longitudinal direction


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Chemical Shift Imaging (CSI): Overview

= Spectroscopic Imaging (SI)

 Spatial encoding by Phase Encoding


of One, Two, or Three Dimensions
(1D-, 2D-, 3D-CSI)

 Reconstruction of nD-CSI datasets


by nD-FFT (+ 1 FFT for spectral dim.)

 Representation of Results
 Single spectra related to single voxels
 Spectral maps
 Metabolite images
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Chemical Shift Imaging (CSI): Overview

 Advantages
 Acquisition of multiple voxels
 Metabolite images
 (many voxels within the same dataset)

 Disadvantages
 larger VoI
 more difficult and less opimal shimming
 Voxel bleeding
 (large datasets)
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CSI – Spin Echo

90° 180° 180° data acquisition

TE1/2 TE1/2 - TE2/2 TE2/2

G read

G phase

G slice
spoiler

 2D hybrid spin-echo CSI


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CSI – k-space sampling

Elliptical
kx
NA ky
Full
averages

Weighted
kx
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CSI – k-space sampling

The effect on SNR

Phantom-Measurement
TR = 1.5 s, NA = 4

Phase S/N Acqu. Time Acqu. Time


encoding 2D: 16 x 16 3D: 8 x 8 x 8
(min.s) (min.s)
FULL 1.0 26 51
ELLIPTICAL 1.0 15 (58%) 20 (39%)
WEIGHTED 1.0 7 (28%) 8 (16%)
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Measure and Invoke Post-Processing

Apply protocol
 starts measurement

Double-click on raw-data icon


 activates
Spectroscopy Post-Processing 
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1HMRS Results
Automized Acquisition and Quantitation

Spin-Echo SVS, VoI = 2 x 2 x 2 cc, TE = 135 ms, TA = 6’ 24 s

Parietal lobe
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1HMRS Results
Automized Acquisition and Quantitation

Spin-Echo SVS, VoI = 2 x 2 x 2 cc, TE = 30 ms, TA = 6’ 24 s

Frontal lobe
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Clinical 1H MRS Results: Glioma


courtesy of M. Shapiro M.D., Neurological Imaging Institute, Florida, USA

Abnormality in the pons?

Spin-Echo post CE FLAIR post CE


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Clinical 1H MRS Results: Glioma


courtesy of M. Shapiro M.D., Neurological Imaging Institute, Florida, USA

Spin-Echo SVS, VoI = 3 cc, TE = 135 ms, TA = 6’ 24s

Control Spectrum Healthy Area


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Clinical 1H MRS Results: Glioma


courtesy of M. Shapiro M.D., Neurological Imaging Institute, Florida, USA

Spin-Echo SVS, VoI = 3 cc, TE = 135 ms, TA = 6’ 24s

Tumor Spectrum Biopsy: pontine glioma


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Clinical 1H MRS Results:


acute and subacute demyelinating lesions
courtesy of W. Küker, F. Mehnert , T. Nägele, U. Klose, Dept. of Neuroradiology, University of
Tuebingen, Germany

Acquisition weighted CSI


acquired with 12 channel head coil
+ fully automated postprocessing

a) TSE-FLAIR (TI = 2.5 s):


the acute and subacute lesion is enhanced
b) NAA metabolite image (TE = 135 ms)
a b c) myo-Inositol and
d) Lipid/macromolecule metabolite
image (TE = 30 ms)

Good differentiation of acute and subacute


lesions.

c d
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Clinical 1H MRS Results:


acute and subacute demyelinating lesions
courtesy of W. Küker, F. Mehnert , T. Nägele, U. Klose, Dept. of Neuroradiology, University of
Tuebingen, Germany

a b

Short TE spectra from the the frontal (b) and the dorsal (a) part of the lesion:
a) dorsal: very high lipid/macromolecule signal and slightly decreased myo-Inositol
signal (acute lesion)
b) frontal: strongly increased myo-Inositol (subacute lesion)
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Prostate Cancer
bladder

prostate rectum

urethra

 2nd most cancer-related deaths in men in western countries


 established diagnostic methods (US, MRI, CT) inadequate even
for cancer detection
 gold standard: histopathology of biopsy material
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 combined MR strategy

 T2-weighted MRI
 morphology
 dynamic ce MRI
 vascularity
 spectroscopy
 metabolism

Scheidler, … Kurhanewicz, Radiology 213, 473-480, Nov. 1999:


tumor localization within sextants, 53 patients
MRI + MRS 
specificity = 91 %
sensitivity = 95 %
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Signals of Interest

Citrate:
 Healthy epithelial cells
synthesize and secrete citrate.

High conc. of zinc inhibits the enzyme aconitase (Krebs-cycle). The conc.
of citrate remains high.

 In cancer:
Citrate is significantly reduced or absent

Choline:
 In human cancer:

Changes in cell membrane synthesis and degeneration is


associated with elevation of choline peak.
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Proton 3D CSI Prostate Spectroscopy

 3D CSI with weighted acquisition


 Outer Volume Signal Suppression (OVS)
 Spectral Fat Suppression
  scan time is 7 min.
  nominal voxel size is 6 x 6 x 10 mm3 !

 This examination of the entire prostate takes less than


10 minutes including adjustments!
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Coverage of the entire prostate


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Outer Volume Fat Suppression

 up to 8 saturation bands available

 positioning on 3 localizer images of arbitrary orientation

 CSI VoI and Saturation-Bands can be freely angulated


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Clinical Results*: Prostate cancer

Tumor as seen on a turbo spin echo


coronal image . TR= 4000 ms,
TE= 132 ms.

* Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL
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MR Spectroscopy: Coronal 3D CSI


Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL

Affected
Position of one coronal
section of the 3DCSI data set area
covering the prostate.

Spectra are acquired


from a 16x16 grid as
shown here on the
coronal slice.

Only spectra from


the prostate ( inside
white box) are displayed
and analyzed.
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Spectral Map
Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL

High
Choline

Coronal Spectral Map


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Control Spectra
Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL

Cit

Cho

Cit

Cho

Cit

Cho
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Tumor Spectra
Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL

Cho

Cit

Cho

Cit

Cho

Cit
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Spectral Map and Choline Metabolite Image


Courtesy of A. Heerschap, T. Scheenen, D. Klomp et al. University Hospital Nijmegen, St. Radboud, NL

Spectral map Choline image

Highest choline

concentration
as depicted on

the spectral

map (left) and

on the choline

image (right)
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Differential Diagnosis of Breast Cancer

CE MRI for Breast Cancer examination :


 Sensitivity 94 – 100 %
 Specificity 37 – 94 %  high variability

 Improved variability with


 enhancement kinetics
 MR-spectroscopy

 combined MR strategy
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Will Cho-detection by 1H MRS improve specificity?

 Yeung, Yang, Tse, Radiology, 225:190-197, 2002:

 overall cancer types true positive detection rate: 74%

 sensitivity low for non-infiltrating & high for infiltrating carcinoma

 axillary node metastasis: sens. = 82%, spec. = 100%, acc. = 90%

 all results with respect to FNAB as gold standard

 Katz-Brull, Lavin, Lenkinski, J. Natl. Cancer Inst., 94:1197-1203, 2002

(Meta-Study of 5 original studies)

 benign vs. malignant breast lesions: sens. = 82%, spec. = 85%


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MR Breast - Spectroscopy
Resonance @ 3.25 ppm increases with malignancy
 compounds:

Choline, phosphocholine, glycerophosphocholine and taurin

at 1.5 – 4T not spectrally resolved  termed tCholine,

Yeung DKW et al.

Radiology 225:190-197
(2002)
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Special Sequence

svs_se_bB1 = svs_se + Spectral Suppression

 optimized spectrally selective pulses

 applied twice during TE; TEmin = 100 ms

 lipid and water suppression

 Acquisition using the

Siemens Breast Coil


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Pre-Clinical Results: Control

residual lipid signal


(suppr. factor 220)

no artefactual signal at 3.2 ppm

courtesy of I. Gribbestad et al., St. Olavs Hospital, Trondheim, Norway


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Pre-Clinical Results: Breast Cancer

voxelsize = 3.4 cc, TA = 3 mins. 12 s


courtesy of I. Gribbestad et al., St. Olavs Hospital, Trondheim, Norway
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Pre-Clinical Results: Breast Cancer

lipid signals
water
signals

voxelsize = 2.3 cc, TA = 9 mins. 36 s

courtesy of N.R. Jaganathan et al., AIIMS, New Dheli, India


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Pre-Clinical Results: Lactating Breast

lactose

Cho

voxelsize = 8 cc, TA = 3 mins. 12 s TR/TE = 1500/135 ms

courtesy of N. Salibi, Siemens Medical, USA, and T. Bae, Washington Univ., St. Louis, USA
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Can tCholine be detected in benign lesions only ?

 MRS breast exams @ 4T showed tCho in normal subjects.

 Quantification of tCho is necessary


 Versus ??

 Versus unsuppressed water (BolanPJ, … Garwood M. MRM 50:1134ff 2003)

 Quantification of tCho is also valuable for measuring tumor

response to chemotherapy treatment.


 First promising results showed significant correlation between tCholine decrease and Ki67

decrease (marker for proliferative fraction) after Chemotherapy (Garwood et al. ISMRM ‘03)
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Tim and Spectroscopy

?? ??
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Matrix Coils supported by


Spectroscopy

 Constant phase correction


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Signal Combination
l Si Wi* Si
 phase-coherent, weighted signal addition

leading to optimal SNR


Roemer et al., The NMR Phased Array, MRM, 16, p. 192-225, 1990.

 normalization options:

 to body-coil homogeneity (pre-scan based)

OR

 to Si Ai2

 no restrictions, e.g. support of SVS, 2D & 3D CSI

 storing of uncombined result possible


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Increased SNR especially in


boundary voxels

Matrix Coil Single Array Coil


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Siemens
MR Spectroscopy
helps
You in making Your diagnosis