Susmita Shrestha MR Spectroscopy Bsc. MIT 4rth yr, CMCTH

1. SUSMITA SHRESTHA
Bsc.MIT 4th year, CMCTH
MAGNETIC
RESONANCE
SPECTROSCOPY
(MRS)

2. OBJECTIVES
 Introduction
 Basic principle
 Techniques and physics
 Steps in MRS acquisition
 Metabolites (normal and abnormal condition)
 Clinical application and limitations
 MRS artifacts
 MRS of other nuclei
 Some cases
 Key points
 Questions

3. INTRODUCTION
 Noninvasive physiologic imaging technique that measures relative
levels of various tissue metabolites in form of spectrum.
 In 1991, Richard Ernst developed high resolution NMR Spectroscopy.
 Theoretically, MRS can be performed with nuclei of 1H, 13C, 23Na and
31P.
 Clinically used are 1H(proton) and 31P (non-proton) spectroscopy.

4. BASIC PRINCIPLES
 Usual MRI images are formed by signal from water and fat
protons
 By comparison, MRS analyzes chemical composition of
tissues by excluding the overwhelming signal from fat and
water protons thereby, detects small metabolites existing in
mM concentrations
 Small metabolites are detected by chemical shift (δ) which is
expressed in terms of parts per million(ppm) and reference
point is Tetramethylsilane (TMS).
 Homogenous magnetic field. In MRI homogeneity required
is about 0.5 ppm whereas for MRS it is about 0.1 ppm
 Shimming
 No frequency encoding gradient in MRS

5. CONTD…
 Size and shape of peaks depends on:
- concentration of active nuclei
- T1, T2 and T2* effects
- overlapping peaks
- splitting by J – coupling.

6. WATER AND FAT SUPPRESSION
 Large water peak must be suppressed to allow visualization of low concentration
metabolites.
 Most common method is a group of CHESS ( chemical shift selective ) pulses
tuned to the water resonance to suppress the water.
 Lipid contamination is problematic in Breast (normal breast contain large amount
of fat), Prostate (small organ located in pelvic fat) and in brain (scalp and marrow
fat).
 Use of OVS (outer volume suppression), Inversion recovery method and Basing
will eliminate unwanted fat signal to reliably measure metabolite concentrations.

7. LOCALIZATION TECHNIQUES IN MRS:
 (Surface coil MRS) :
i) Rotating frame zeugmatography
ii) Topical magnetic resonance (TMR)
iii) Fast rotating gradient spectroscopy (FROGS)
iv) Depth resolved surface coil spectroscopy (DRESS)
 ISIS (Image selected in vivo spectroscopy)______________
 PRESS (Point resolved spectroscopy)__________________ ( Single Voxel)
 STEAM (Stimulated echo acquisition mode)_____________
 CSI(Chemical shift imaging) or SI (Spectroscopic imaging)- (Multi-voxel
spectroscopic imaging)

8. SURFACE COIL MRS
 Small circular wire loop that is positioned adjacent to the site of detection in
such a way that field generated by a coil is orthogonal to the Bo field.
 Advantages:
- To obtain spectra from surface and superficial tumors
 Disadvantages:
- Rough localization
- Inhomogeneous transverse magnetic field.
- Difficulty in assessing VOI.
- Contamination of signals from extraneous tissues.
 For these reasons they were used with other techniques like phased array surface
coil and adiabatic pulse sequences.

9. i) Rotating frame zeugmatography
- method : B1 gradient
- use: spectra from various depth along axis of surface coil
ii) Topical magnetic resonance (TMR)
- method : Bo inhomogeneities
- use : detect signal from a large VOI
iii) Fast rotating gradient spectroscopy (FROGS)
- method : Bo slice selective gradient
- use : detects signal from large VOI

10. iv) Depth resolved surface coil spectroscopy (DRESS)
- method : Bo slice selective gradient with frequency selective
RF pulses.
- use : Can detect signal from slices parallel to the plane of
surface coil.
- disadvantages: reduced sensitivity and significant loss of
signal for metabolites with short T2.

11. IMAGE SELECTED IN VIVO
SPECTROSCOPY (ISIS)
 3 slice selective inversion
pulses are applied in the
presence of three orthogonal
gradients.
 Recorded signal is a free
induction decay (FID)
 It is used in 31p
spectroscopy.
 The major limitation is the
subtraction errors.

12. STIMULATED ECHO ACQUISITION MODE
(STEAM)
 The VOI is excited by three 90
degree RF pulses.
 Only the part of available signal
produces the stimulated echo so the
signal is weak.
 Use for short TE(20-30ms)
 Exclusive use of 90 degree RF
pulses.
 Reduced J-coupling modulation.
 Major signal – noise ratio penalty.
Timing diagram of a STEAM sequence

13. POINT RESOLVED SPECTROSCOPY (PRESS)
 One 90 degree and two 180
degree RF pulses are applied.
 Use for long TE (135,270ms)
 Strong signal.
 Better SNR.
 High J –coupling modulation.
 Use of multiple 180 degree
pulses.
Timing diagram of a PRESS sequence

14. CHEMICAL SHIFT IMAGING (CSI) OR
SPECTROSCOPIC IMAGING (SI)
 Multivoxel spectroscopic technique.
 Data is collected in absence of readout
gradient.
 Advantage - acquisition of the spectral data
of smaller voxels from
large area coverage
- high spatial resolution
- ability to reconstruct the low
resolution metabolite images.

15. CONTD…..
 Disadvantage – signal from a voxel is prone to contamination coming from
outside the VOI
- individual spectra being offset in frequency.
 Recently, hybrid SV – SI pulse sequence has been developed in an approach to
acquire in vivo data
 The advantage of SI to localize multiple voxels + use of SV method to preselect
large VOI.

16. SINGLE VOXEL V/S MULTI VOXEL

17. STEPS IN MRS ACQUISITION
 Patient positioning
 Global shimming
 Acquisition of MR images for localization
 Selection of MRS measurements and parameters
 Selection of VOI
 Local shimming
 Water suppression
 MRS data collection
 Data processing and display
 Interpretation

18. VARIATIONS OF TE IN SPECTRA

19. OBSERVABLE METABOLITES
Metabolite Location
ppm
Normal function Increased Decreased
NAA 2 Nonspecific neuronal
marker
Canavan’s disease stroke, dementia,
hypoxia, neoplasia,
abscess
(absent in case of mets)
Glutamate / Glutamine
(Glx)
2.1- 2.4 Neurotransmitter Hypoxia, hepatic
encephalopathy
Hyponatremia
Succinate 2.4 Part of TCA cycle Brain abscess
Creatine 3.03 Cell energy marker Trauma, hyperosmolar
state
Stroke, hypoxia,
neoplasia
(absent in case of mets)

20. CONTD….
Metabolite Location
ppm
Normal function Increased Decreased
Choline 3.2 Marker of cell
membrane
Neoplasia,
demyelination (MS)
Hypomyelination
Myoinositol 3.5 & 4 Astrocyte marker Gliosis, neonates,
schwanoma, tuberous
sclerosis,
Demyelinating
diseases
Ischemia, neoplasm,
demyelination

21. CONTD…
Metabolite Location
ppm
Normal function Increased
Lipids 0.9 & 1.3 Cell membrane component Hypoxia, trauma, high grade neoplasia.
Lactate 1.3 Denotes anaerobic
glycolysis
Hypoxia, stroke, necrosis, mitochondrial
diseases, neoplasia, seizure
Alanine 1.5 Amino acid Meningioma, pyogenic abscess
Acetate 1.9 Anabolic precursor Abscess ,
Neoplasia,

22. SHORT TE 35(used for metabolic and diffused
disease)
 MI
 LACTATE
 LIPIDS
 GLUTAMATE / GLUTAMINE
BOTH SHORT 35 AND LONG TE 144 (better
definition of peaks used for focal lesions)
 NAA
 CREATINE
 CHOLINE
 LACTATE signal lowered
METABOLITES

23. HUNTER’S ANGLE
Gray matter
has more
Creatine
NAA
Cr
cho
Mi Glx
lac lip

24. CLINICAL APPLICATION OF MRS
1) Brain tumors
 There is increased in choline , lactate and
lipid in tumors .
 There is reduction in NAA and Cr in
tumors.
- MRS in tumor evaluation
- In treatment planning
- In treatment monitoring
Cho map for biopsy guidance

25. CONTD…

26. 2) RADIATION NECROSIS V/S RECURRENT
TUMORS
 True necrosis - an absence of the typical brain metabolite signals and an
increase in lipid signals.
 Radiation induced changes - MR spectrum may reflect a brisk
inflammatory process – MRS measuring signals from the activated
immune cells that are predominant and are characterized by elevated
Cho.
 In Radiation necrosis - typically a slight elevation of Cho and often the
presence of the lipid resonance.

27. CONTD…
 To differentiate Radiation Necrosis from Recurrent tumor, combination of perfusion
imaging with MR spectroscopy can be very useful especially when they provide
concurrent findings.
 For example, low CBV in perfusion MRI and only a slight elevation of Cho/Cr in
the MR spectrum suggest radiation necrosis.
 Conversely, high CBV and an MRS displaying high Cho would likely represent
recurrent tumour as the predominant process.

28. Radiation change

29. 3) ACUTE ISCHEMIC STROKE
 Most reliable clinical method for identifying the ischemic core and
penumbra in ischemic stroke is the use of diffusion and perfusion MRI.
 MRS can be useful in assessing the severity of ischemia within the
region that is being perfused by collateral flow.
 With further reduction of perfusion, progression to frank ischemia will
result in the elevation of lactate and the reduction of NAA.

30. CONTD…
MRS of a patient with an acute stroke

31. 4) EPILEPSY
 During seizure, the metabolic demands of brain cells can exceed the supply of oxygen
and nutrients to the portion of the brain that is undergoing enhanced electrical
activity.
 Metabolic changes can be detected by MRS, including the production of lactate and,
if prolonged, the reduction of NAA .
 Abnormalities, including the elevation of lactate, can still be observed some time after
seizure activity ceases.
 The purpose is to help localize the source of the seizures.
 Most common clinical scenario - Temporal lobe epilepsy (TLE).

32. Temporal lobe epilepsy

33. 5) METABOLIC DISORDERS AND WHITE MATTER
DISEASES
 MRS is valuable in paediatric brain disorders that are due to inborn errors of
metabolism :
- Leukodystrophies
- Mitochondrial disorders and
- Enzyme defects that cause an absence or accumulation of metabolites.
 MRS can be diagnostic for some of these diseases.
 An example of such a disorder is Canavan disease.
 Elevation of lactate doublet is seen in mitochondrial disorder like MELAS
(mitochondrial encephalopathy lactic acidosis and stroke).

34. Lactate peak in metabolic disorders

35. 6) NEURO AIDS
 The first reports on the use of MRS in NeuroAIDS were published the early 1990s.
 Demonstrated a significant reduction in levels of NAA in the brains of these
patients .
 Subsequently it was shown that earlier in the disease, elevations of Cho , MI , and
sometimes Cr preceded a drop in NAA.
 These findings suggested that a cerebral inflammatory process occurred before
neuronal injury, and that neuronal injury occurred later, after the inflammatory
process had persisted for some time.

36. CONTD….
 MRS may help to differentiate lymphoma, toxoplasma and
progressive multifocal leukoencephalopathy (PML)
 Lymphoma – shows elevation in lactate, lipids and choline; and
reduction in NAA , Cr and MI
 Toxoplasma – shows elevation in lipids and lactate; and reduction in
all other metabolites.
 PML – shows elevation of cho and slight elevation of lactate, lipids
and MI; and reduction in NAA and Cr.

37. 7) BREAST SPECTROSCOPY
 Main purpose is to distinguish
benign from malignant tumors
 Performed using surface coil and
SVS technique with fat
suppression and long TE value
 Major peak characteristics of
cancer is total choline (tCho) at
3.2 ppm

38. 8) PROSTATE MRS
 Focused on detection and localization of
cancer
 Both endorectal and pelvis phased – array
coils are needed.
 Outer volume fat suppression and careful
shimming mandatory.
 Multi – voxel spectroscopy is required
 Recommended sequence is 3D PRESS
CSI with voxel size in the range of 6 – 10
mm , short TR ~ 1000ms and TE ~
125ms at 1.5 T.

39.  Dominant MRS peak for normal prostate is citrate (δ = 2.2 ppm)
 Small peaks from choline, creatine and polyamines also seen.
 In cancer, citrate and polyamines decreases while choline increases

40. 9) MRS OF MSK
 Compared to its uses in the brain and
other body regions, spectroscopy has
had rather limited application in the
MSK system.
 SVS techniques are preferred using
water suppressed PRESS sequence
with TE values ( 130 – 144ms)
 Spectrum dominated by
Intramyocellular (IMCL) and
Extramyocellular (EMCL) lipids.
 Elevated choline may indicate
malignancy.

41. 10) MRS OF LIVER
 Primary role is to quantify fat fraction
in non – alcoholic liver disease
 STEAM SVS breath - hold technique
typically used with long TR and short /
multiple TEs
 Neither fat nor water suppression
pulses are used
 Areas under T2- corrected and modeled
water and fat peaks are used to
calculate fat fraction i.e. Af / Af + Aw

42. LIMITATIONS OF CLINICAL MRS
 Operator and interpreter dependent.
 Positioning of voxel is a very important step in performing MRS, which if not
accurate will obtain contaminated or sub optimal spectra.
 Difficult to perform MRS on smaller lesions.
 susceptibility broadening effect in areas of basal ganglia resulting in lower-quality
spectra.
 Proximity of the VOI to the scalp can result in contaminating lipid signals.

43. MRS ARTIFACTS
1) Poor shimming – recognized by
spectral lines that are too wide , short and
poorly separated.
2) Incomplete water suppression – lost in
background noise and metabolite spectra
may be inapparent

44. 3) Phasing errors – results when
absorption and dispersion modes are
mixed. Therefore, spectrum is adjusted
to display optimal absorption mode
waveform.
4) Spectral contamination – refers to
erroneous assignment of metabolite
signals to the wrong voxel. So, the
effects can be reduced through digital
filtering techniques and increasing
number of voxels.

45. 5) Chemical shift displacement – has
identical nature to fat – water artifacts seen
on conventional MRI. Therefore, solution is
to employ larger bandwidth RF pulses and
stronger imaging gradients.

46. MRS OF OTHER NUCLEI
 Use of non – hydrogen nuclei for NMR is commonly called multi – nuclear
spectroscopy
 Commonly used MNS nuclei include:
1) 31p
 Phosphorus has 100% natural abundance. However, lower nuclear sensitivity than 1H
so weaker signal.
 Relatively small (<10) and more widely separated peaks than 1H
 To counteract scalar J – coupling effect decoupling is commonly performed.
 Requires separate RF front end and coils tuned to its lower resonant frequency. i.e. the
dual –tuned coil.
 Technique include : ancillary signal enhancement using proton decoupling and Nuclear
Overhauser Enhancement (NOE) stimulation of 1H

47. 31P SPECTRA DIFFER AMONG VARIOUS ORGANS

48. 2) 13C
 Difficult to perform due to low natural abundance 1.1%
and low nuclear sensitivity.
 Special equipment, longer imaging time and decoupling
technique required.
 Limited success has been reported studying glycolysis,
dynamics of Krebs cycle and in certain aspects of
neurochemistry
3) 23Na
 23Na is NMR active, with resonance frequency about ¼
that of 1H
 No natural chemical shift dispersion, so not useful for
MRS, but can be used for MRI
 Quadrupolar relaxation produces very short T2 value in
tissues.

49. Magnetic resonance properties of some medically important nuclei

50. MENINGIOMA
SOME CASES….

51. MEDULLOBLASTOMA

52. MULITPLE TUBERCULOMA

53. ALZHEIMER’S DISEASE

54. CANAVAN’S DISEASE

55. LYMPHOMA

56. PYOGENIC ABSCESS

57. CHOROID PLEXUS PAPILLOMA

58. KEY POINTS
 High Cho - High tumor cell density & high vascular proliferation.
 Low Cho and elevation of lipids - Necrosis.
 Cho higher enhancing rim -may be the faster growing side of the
tumor.
 Vasogenic edema -Normal Cho and slightly decreased NAA.

59. QUESTIONS ???
 Explain basic principles of MRS
 Why do some spectra split into smaller peaks while others do not?
 How do you suppress signal from fat and water in MRS?
 How do you localize MRS signal while frequency-encoding gradient cannot be
used?
 Difference between single and multi-voxel MRS
 Which of the MRS localization technique is most clinically used and why?
 How does variations of TE affects the spectral lines?
 What is Hunter’s angle? What does it mean if the peaks do not line up?
 What are the various clinical application and limitations of MRS?
 How does various metabolites response accordingly to disease state?

60. THANK YOU