1. Introduction to Magnetic Resonance Spectroscopy
Atiyah Yahya
Ph.D., FCCPM, P.Eng.
Department of Medical Physics, Cross Cancer Institute Department of Oncology, University of Alberta Edmonton, AB, Canada

2. Conflicts of Interest
None.

3. Learning Objectives
At the end of the session the audience should have a basic understanding of the acquisition of MRS spectra, the challenges involved in interpreting spectra and some MRS quality control tests.

4. Introduction to NMR Preparation of the nuclear system
1H nuclei
z, Bo Mo y
Excitation of the nuclear system Mo Bo y x z
o = Bo x
Absence of magnetic field
Presence of a static field Bo
RF coil: A resonating LC circuit tuned to o creates an excitation pulse.
90 pulse

5. Acquisition of the nuclear signal
RF coil: A resonating LC circuit tuned to o C C
To Receiver M C o
spectrum  FT
time
signal

6. How can we use NMR spectroscopy?
Non-invasive biochemical analysis.
Metabolite concentrations in the brain.
1H is the most abundant and most sensitive NMR viable nucleus in the body.
NMR spectrum from a rat brain at 9.4 T.
Tkac et al. (1999)

7. Metabolite concentrations are on the order of a few millimoles (mM)
About 10-4 times the concentration of water.
Water suppression techniques need to be implemented to minimize the water signal.
Gradient RF
Frequency selective water excitation
time

8. Two important phenomena of spectroscopy
Chemical shift
Chemical shielding arises because nuclei in different chemical environments are bonded by different electronic orbitals and therefore experience different electronic magnetic fields.
The electronic magnetic fields give rise to a shift in the resonance frequency called the “chemical shift”.
electron
Beff = Bo(1-)
nucleus

9. TMS is tetramethylsilane, (CH3)4Si, and its proton signal is defined as the zero ppm reference.
Chemical shift = a = (a - TMS)/o x 106 ppm
ppm = parts per million
At Bo = 3 T, fo = MHz and 1 ppm corresponds to Hz.
Expressing chemical shifts in ppm makes them field strength independent.
The chemical shift frequency difference between peaks increases linearly as function of Bo.
Spectral resolution improves with increased Bo.

10. 3 T 9.4 T mI mI Glx Tau + mI Lac Glx + mI Cho Cr mI Cr Lac Glu mI Glx
Gln
Lac
Chemical shift (ppm)

11. Scalar coupling (J-coupling)
Nuclei also interact with each other, via the electrons in the bonds joining the nuclei, causing splitting in the resonant peaks of the spectrum.
Example:
C C H J
CH3-CH-COOH OH
Lactate
For lactate (Lac), J is about 6.9 Hz.

12. Peaks are separated by J Hz
CH3-CH-COOH OH
Lactate
C C H J
Peaks are separated by J Hz
chemical shift (ppm) CH
CH3

13. 3D-localization using PRESS (Point RESolved Spectroscopy)
Acquisition
90x
180y
180y RF
gradients
time
TE1/ (TE1+TE2)/ TE2/2
Gx Gy Gz
time
= slice selection gradients
= spoiler gradients
= slice selective pulses

14. STEAM Sequence
STimulated Echo Acquisition Mode – another single shot localization MRS sequence.
90x
90x
90x RF
gradients
time
TE/ TM TE/2
Gx Gy Gz
time
= slice selection gradients
= spoiler gradients
= slice selective pulses

15. Typical brain spectrum
chemical shift (ppm)
mI+Tau
Cr+PCr
Glx
mI+Glx
mI+Gly
Cho
NAA+GABA
Asp
NAA
Glx+GABA 3T
8 cm3 volume.
Healthy volunteer.
PRESS sequence (TE = 30 ms, TR = 3 s)

16. Quantification Challenges
chemical shift (ppm)
mI+Tau
Cr+PCr
Glx
mI+Glx
mI+Gly
Cho
NAA+GABA
Asp
NAA
Glx+GABA
Overlap of peaks
Macromolecule
baseline
Spectral fitting software
Long TE to enable macromolecule T2 decay
Spectral editing

17. Example of spectral editing: long-TE PRESS for myo-inositol
Cr + PCr + GABA
Cr + PCr
Cho
TE1=TE2=15ms
mI+Glx
mI+Gly
Glx
mI+Tau
Cho
Cr + PCr + GABA
TE1 = 36 ms TE2 = 160 ms
Cr + PCr
mI+Gly
Glx
chemical shift (ppm)
Kim et al. Magnetic Resonance in Medicine, 53, p.760, 2005

18. Response of glutamate to PRESS
TE1 = TE2 = 10 ms
TE1 = TE2 = 20 ms PQ MN PQ MN A M N P Q
Glu O C 1 2 5 3 4 A A
TE1 = TE2 = 30 ms
TE1 = TE2 = 40 ms
TE1 = TE2 = 50 ms
TE1 = TE2 = 60 ms
ppm
ppm

19. Spectroscopic imaging
NAA
NAA
Cho Cr
Cho Cr
NAA
NAA
Cho Cr
Cho Cr

20. Spin echo spectroscopic imaging
= slice selective pulses
90x
180y
= slice selection gradients
time
TE/ TE/2
= spoiler gradients Gz
time
= phase encode gradients Gx
time Gy
time

21. Voxel resolution = 200/12  16.7 mm
For example:
Field of view (FOV) = 200 mm
12 x 12 phase encodes
Voxel resolution = 200/12  16.7 mm
Voxel volume = (16.7 x 16.7 x slice thickness) mm3
Acquisition time =
12 x 12 x repetition time
200 mm
200 mm

22. Examples of metabolites relevant to tumors
NAA = N-acetyl aspartate
Glx = glutamate + glutamine
Cr = creatine
Cho = choline
Ino = inositol
Spectrum from white matter.
Spectrum from a low grade oligodendroglioma.
Lac
Lac = lactate
Spectrum from a high grade oligodendroglioma.
Rijpkema et al., NMR in Biomedicine, 2003

23. Quality Control for MRS
Use a phantom dedicated for MRS quality control (QC)
Use the same setup each time and the same RF coil e.g. head coil
Establish baseline values

24. D-C. Woo et al., Development of a QA phantom and protocol for proton magnetic resonance spectroscopy, Concepts in Magnetic Resonance, v. 35B, p. 168 (2009)
D. Drost et al., Proton magnetic resonance spectroscopy in the brain: Report of AAPM MR task group #9, Med. Phys., v. 29, p (2002)
S. Nicolosi et al., Minimal protocol for MRS quality control and acceptance testing for Philips-Achieva MRS tool,

25. Example Protocol
3 T, transmit receive head coil, double compartment MRS phantom placed at coil centre
2 x 2 x 2 cm3 PRESS voxel in centre of inner compartment, 1 x 1 x 1 cm3 in outer compartment
Spectral width = 2000 Hz, number of samples = 4096, number of averages = 32, echo time = 100 ms, repetition time = 4 s
6 cm
9 cm

26. Double compartment phantom to verify spatial localization
10 mM creatine (Cr)
Double compartment phantom to verify spatial localization
20 mM acetate

27. 10 mM creatine (Cr)
20 mM acetate

28. Resonance Frequency
Record resonance frequency of water, e.g. 127,806,294 Hz
Record receiver gain
Record chemical shifts of peaks

29. SNR Record peak area Peak height
standard deviation of noise
Record peak area

30. Peak Linewidth (FWHM)
1.6 Hz

31. Water Suppression Record height of residual peak
Or acquire a non-suppressed water spectrum and determine % suppression

32. Questions? Concluding Remarks Overview of MRS Techniques used in MRS
Quantification challenges
Spectroscopic imaging
QC protocol for MRS
Questions?