MRI spectroscopy- Its Application, Principle & Techniques

1. MAGNETIC RESONANCE
SPECTROSCOPY
(MRS)

2.  Introduction
 Physics
 Interpretation
 Indications
 Cases
 Summary

3.  Magnetic resonance spectroscopy (MRS) is a means of
noninvasive physiologic imaging of the brain that measures
relative levels of various tissue metabolites
 Purcell and Bloch (1952) first detected NMR signals from
magnetic dipoles of nuclei when placed in an external
magnetic field.
 Initial in vivo brain spectroscopy studies were done in the
early 1980s.
 Today MRS-in particular, IH MRS-has become a valuable
physiologic imaging tool with wide clinical applicability.

4. PRINCIPLES:
• The radiation produced by any substance is dependent on
its atomic composition.
• Spectroscopy is the determination of this chemical
composition of a substance by observing the spectrum of
electromagnetic energy emerging from or through it.
• NMR is based on the principle that some nuclei have
associated magnetic spin properties that allow them to
behave like small magnet.
• In the presence of an externally applied magnetic field,
the magnetic nuclei interact with that field and distribute
themselves to different energy levels.
• These energy states correspond to the proton nuclear
spins, either aligned in the direction of (low-energy spin
state) or against the applied magnetic field (high-energy
spin state).

5. MR Spectroscopy
Noninvasive means of assessing the
biochemical and metabolic processes in
intracranial tissues without ionizing
radiation.
For the brain in particular, MRS hasbeen a
powerful research tool and provide
additional clinical information for several
disease such as brain tumors, metabolic
disorders, and systemic diseases

6. There are numerous metabolites found in the
human brain.
Fortunately, only several of them are useful in
spectroscopic studies.
There is evidence that the normal metabolites in the
brain vary with according to the patient's age.
The changes are most noticeable during the first
three years of life.

7.  If energy is applied to the system in the form of
a radiofrequency (RF) pulse that exactly
matches the energy between both states. a
condition of resonance occurs.
 Chemical elements having different atomic
numbers such as hydrogen ('H) and
phosphorus (31P) resonate at different Larmor
RFs.

8. N-ACETYLASPARTATE (NAA)
NAA is the marker of neuronal density and viability.
•It is present in both gray and white matter and the
difference in concentration is not clinically significant.
•
•
NAA is detected by the its N-acetyl methyl group.
Its concentration appears to decrease with any brain
insults such as infection, ischemic injury, neoplasm, and
demyelination process.
NAA is not in found in tumors outside the central nervous
system (CNS) such as meningioma.
NAA is the tallest peak in the proton MR spectrum and it is
assigned at 2.0ppm. Additional smaller peaks may be
seen at 2.6 and 2.5 ppm.
•
•

10. Choline
The choline peak receives contribution from
glycerophosphocholine, phosphocholine, and
phosphatidylcholine.
It is the precursor of acetyl choline and
phosphatidylcholine.
Acetylcholine is an important neurotransmitter and
the latter is an integral part of cell membrane
synthesis.
Disease processes affecting the cell membrane and
myelin can lead to the release of
phosphatidylcholine.
Thus, elevation of choline can be seen during
ischemic injury, neoplasm or acute demyelination
diseases.
Choline is the second largest peak and assigned to
3.2 ppm.

12. Creatine (Cr)
The Cr peak receives contribution mainly from
creatine, and creatine phosphate.
The phospocreatine supplies phosphate to
adenosine diphosphate (ADP) to form adenosine
triphosphate (ATP) with the release of creatine.
The overall level of total creatine in normal
brain is fairly constant.
Reduced Cr level may be seen in pathologic
processes such as neoplasm, ischemic injury,
infection or some systemic diseases.
Most metastatic tumors to the brain do not produce
creatine since they do not possess creatine
kinase.
Cr is the third highest peak and is assigned to 3.03
ppm. It is usually seen next to the right of choline.

14. Lactate
Lactate has a molecular structure of CH3-COH2-
CO2.
Lactate levels in the brain are normally are very low
or absent. When oxygen supply is depleted, the
brain switches to anaerobic respiration (Not from
O2) for which one end product is lactate.
Therefore, elevated lactate peak is a sign of
hypoxic tissue.
Low oxygen supply can result from decreased oxygen
supply or increased oxygen requirement.
The former may be seen in vascular insults, or
hypoventilation and the latter may be seen in neoplastic
tissue.

15. Lactate peak occurs at twodifferent locations.
The lower field peak (a doublet) occurs at
approximately 1.32 ppm.
The other peak (a quartet) is seen at 4.1 ppm and
this is very close to the water peak (4.7 ppm).
– usually suppressed during data processing.

17. Myo-Inositol (mI)
Myo-Inositol is a glucose-like metabolite and it
involves primarily in hormone-sensitive
neuroreception. It is found mainly in astrocytes
and helps to regulate cell volume.
Elevated level of mI would be seen where there
is glial cell proliferation as in gliosis.
The main mI peak is assigned to 3.56 ppm and
additional peak may be seen at 4.06 ppm

19. Lipids
Lipids are composition of triglycerides, phospholipids, and fatty
acids.
These substances are incorporated into cell membranes and
myelin.
Lipid peak should not be seen unless there is destructive
process of the brain including necrosis, inflammation or
infection.
Lipids have a very short T1 relaxation time and are
normally not seen unless short TEs are utilized.
Lipid resonance at 1.2 ppm can sometimes obscure the lactate
peak at 1.32 ppm.
Fat in the cranium can contaminate the true disease process
if the voxels are placed too close the cranium.

20. Glutamate and Glutamine (Glx)
Glutamate is an excitatory neuro transmitter
in mitochondrial metabolism.
Glutamine and glutamate resonateclosely together.
Their sum is often designated as Glx and is assigned
between 2.1 and 2.5 ppm.

22. SINGLE-VOXELMR
SPECTROSCOPY
Lessadvance.
Volume averaging
Small area ofcoverage.
acquires spectrafrom
single smallvoxel.
short acquisitiontimes.
Histologically simpler
lesions.
MR SPECTROSCOPIC
IMAGING/MULTI-VOXEL.
more technicallyadvanced
technique.
small voxel sizedec.
volume averaging
large volume ofcoverage
acquires spectra from
numerous smallvoxels.
long acquisitiontimes.
For complexlesions

23. MULTI VOXEL SPECTROSCOPY
Multivoxel spectroscopy can be used to obtained
one, two or three dimensional localization.
The major engine behind multi voxel is
CHEMICAL SHIFT IMAGING (CSI).
This technique is developed to obtain separate
images from water and fat bound protons.
It is referred as Magnetic Resonance
Spectroscopic Imaging(MRSI).

24. It obtains simultaneously many voxels and
spatial distrubution of the metabolities in a
single sequence.
Large volume of coverage.
It is used for complex lesions.
Long acquisition time (6-12 min).
Time of echo:35 and 144 ms.

25. Echo-Time
As in MR imaging, the echo time affects the
information obtained with MRS.
Short TE refers to a study in which it varies from 20
to 40 ms.
It has a higher SNR and less signal loss due to T2
and T1 weighting than long TE.
These short TE properties result in a spectrum with
more metabolites peaks, such as myoinositol and
glutamine-glutamate which are not detected with
long TE .

26. •MRS spectra may also be obtained with long TEs,
from 135 to 288 ms.
•With a long TE of 270 msec, only metabolites with
a long T2 are seen, producing a spectrum with
primarily NAA, creatine, and choline.
•One other helpful TE is 144 msec because it
inverts lactate at 1.3 ppm.
•With TE of 270-288 ms there is a lower SNR and
the lactate peak is not inverted

27. Planning of MRS
The ROI will be placed at the center of the enhancing
tumor covering the lesion and the normal brain as much
as possible but excluding the subcutaneous fat and
sinuses.

30. Normal MRS

32. Lymphoma

33. Anaplastic Astrocytoma

34. Glioma

35. MRS TECHNIQUES
Single Volume MRS
STEAM (Stimulated Echo
Acquisition Mode)
PRESS (Point Resolved
Spectroscopy)
Short TE can be used to
detect glutamate,
glutamine, myoinositol
Not possible
Chemical shift selective
pulse used to suppress
water signal can be given
throughout volume
localisation phase
Can be given only at
preparation phase
Factor of 2 loss in signal
intensity
Factor of 2 gain in signal
intensity
Susceptible to motion Not affected by motion
Multivolume MRS- multiple adjacent volume over a large region of interest
can be assessed in a single measurement. Acquisition time is 6-12 min.

36. TECHNIQUE:




 Single volume and Multivolume MRS.
 1) Single volume:
Stimulated echo acquisition mode (STEAM)
Point-resolved spectroscopy (PRESS)
It gives a better signal-to noise ratio
 2) Multivolume MRS:
chemical shift imaging (CSI) or spectroscopic imaging (SI)
 Much larger area can be covered, eliminating the sampling error to an
extent but significant weakening in the signal-to-noise ratio and a longer
scan time.
 Time of echo: 35 ms and 144ms.
 Resonance frequencies on the x-axis and amplitude (concentration) on the
y-axis.

37. NORMALMRS CHOLINE NAA CREATINE

38.  MRS of white matter in a normal brain. (A) Long TE spectra have
less baseline distortion and are easy to process and analyze but
show fewer metabolites than short TE spectra. Also, the lactate
peaks are inverted, which makes them easier to differentiatethem
from lipids.
(B) Short TE demonstrates peaks attributable to more metabolites,
including lipids, glutamine and glutamate, and myo-inositol

39. MULTI VOXEL MRS

40. Metabolite
OBSER
V
Location
ppm
ABLE METAB
Normal function
OLITES
Increased
Lipids 0.9 & 1.3 Cell membrane Hypoxia, trauma, high grade
component neoplasia.
Lactate 1.3 Denotes anaerobic Hypoxia, stroke, necrosis,
TE=272 glycolysis mitochondrial diseases,
(upright) neoplasia, seizure
TE=136
(inverted)
Alanine 1.5 Amino acid Meningioma
Acetate 1.9 Anabolic precursor Abscess ,
Neoplasia,

41. PRINCIPLE METABOLITES
Metabolite Location
ppm
Normal
function
Increased Decreased
NAA 2 Nonspecific
neuronal
marker
(Reference for
chemical shift)
Canavan’s
disease
Neuronal loss,
stroke, dementia,
AD, hypoxia,
neoplasia,
abscess
Glutamate ,
glutamine,
GABA
2.1- 2.4
Neurotransmitt
er
Hypoxia, HE Hyponatremia
Succinate 2.4 Part of TCA
cycle
Brain abscess
Creatine 3.03 Cell energy
marker
(Reference for
metabolite
ratio)
Trauma,
hyperosmolar
state
Stroke, hypoxia,
neoplasia

42. Metabolite Location
ppm
Normal
function
Increased Decreased
Choline 3.2 Marker of cell
memb turnover
Neoplasia,
demyelination
(MS)
Hypomyelinatio
n
Myoinositol 3.5 & 4 Astrocyte
marker
AD
Demyelinating
diseases

43. METABOLITE
RATIOS:
Normal abnormal
NAA/ Cr 2.0 <1.6
NAA/ Cho 1.6 <1.2
Cho/Cr 1.2 >1.5
Cho/NAA 0.8 >0.9
Myo/NAA 0.5 >0.8

44. MRS
Dec NAA/Cr
Inc acetate,
succinate,
amino acid,
lactate
Neuodegener
ative
Alzheimer
Dec
NAA/Cr
Dec NAA/
Cho
Inc
Myo/NAA
Slightly inc Cho/ Cr
Cho/NAA
Normal Myo/NAA
± lipid/lactate
Inc Cho/Cr
Myo/NAA
Cho/NAA
Dec NAA/Cr
± lipid/lactate
Malignancy
Demyelinating
disease Pyogenic
abscess

45. CLINICAL APPLICATIONS OF MRS:







 Class A MRS Applications: Useful in Individual Patients
1) MRS of brain masses:
Distinguish neoplastic from non neoplastic masses
Primary from metastatic masses.
Tumor recurrence vs radiation necrosis
Prognostication of the disease Mark
region for stereotactic biopsy.
Monitoring response to treatment.
Research tool
2) MRS of Inborn Errors of Metabolism
Include the leukodystrophies, mitochondrial disorders, and enzyme defects
that cause an absence or accumulation of metabolites

46. CLASS B MRS APPLICATIONS: OCCASIONALLY USEFUL IN
INDIVIDUAL PATIENTS
1) Ischemia, Hypoxia, and Related Brain Injuries
 Ischemic stroke
Hypoxic ischemic encephalopathy. 2)Epilepsy
Class C Applications: Useful Primarily in Groups of Patients (Research)
 HIV disease and the brain
 Neurodegenerative disorders
 Amyotrophic lateral sclerosis
 Multiple sclerosis
 Hepatic encephalopathy
 Psychiatric disorders

47. A 50 yr M with fever, headache and Lt hemiparesis
B, Axial T2-weighted image showing ring
lesion with surrounding hyperintensity and
mass effect.
C, Axial contrast-enhanced T1W image
shows a ring-shaped cystic lesion and
surrounding edema.
D, DWI shows marked hyperintensity in
the cavity and slight iso- to hypointensity
surrounding the edema.
E, ADC map reveals hypointensity in the
cavity, representing restricted diffusion,
and hyperintense areas surrounding the
edema.
DDx- ?abscess, ?tumor
F ,G. MRS from the abscess cavity show
peaks of acetate (Ac), alanine (Ala),
lactate (Lac), and amino acids (AA). At a
TE of 135 (G), the phase reversal
resonances are well depicted at 1.5, 1.3,
and 0.9 ppm, which confirms the
assignment to alanine, lactate, and amino
acids, respectively.
Dx- Pyogenic abscess

48. A 67 YR M WITH POSTERIOR FOSSA SOL
B. Axial T2WI showing hyperintense mass
lesion in Rt cerebellum. Box in the center of
the lesion represents the 1H-MRS volume of
interest.
C, Axial contrast-enhanced T1W image shows
a ring-enhanced lesion in the right cerebellum.
D, DWI shows markedly low signal intensity in
the necrotic part of the tumor.
E, ADC map reveals high signal intensity in the
necrotic part of the tumor that is similar to that
of CSF, reflecting marked diffusion.
DDX- ?tumor
F ,G. MRS from the necrotic center of the
tumor show a lactate (Lac) peak at 1.3 ppm
that is inverted at a TE of 135. No amino acid
or lipid peaks seen
Dx- tumor
Biopsy revealed metastasis from primary lung
adenocarcinoma

49.  Serial magnetic resonance spectroscopic data from a 25-year-old lady
who was under 6-monthly imaging follow-up for a low-grade glioma. A.
Voxel (open square) is situated in the bulk of the tumour, which is
appreciated as an ill-defined area of T2-weighted hyperintensity within
the cingulate gyrus of the right frontal lobe. B. Initial spectra at
presentation demonstrates abnormal Cho/NAA area ratio of 1.4. Note
the absence of lactate at 1.33ppm. C. Spectroscopy 6-months later
demonstrates deterioration in the Cho/NAA area ratio (now 2.21) and
the new presence of an inverted lactate peak

50. A 48 Y F WITH HEADACHE AND LEFT
HEMIPARESIS
A, Coronal contrast-enhanced T1-weighted
MR image shows a large right temporal
mass with rich contrast uptake with
extensive midline shift.
B, Spectrum of the lesion shows increased
Cho/Cr ratio and an absence of NAA.
There is an alanine (Ala) doublet at 1.45
ppm and lipid (lip) signals at 0.8 to 1.2 ppm
Dx- Meningioma

51. A 27 Y M WITH MULTIPLE NODULAR
LESIONS IN BRAIN
A.T1WE at midbrain level shows
nothing remarkable
B. Contrast enhanced T1 W image
revealed multiple small nodular
areas of enhancement
predominantly located at gray
white junction.
DDx- ?Multiple tuberculoma,
?Multiple NCC
C. MR spectroscopy (A; TE = 35ms).
peaks A and B at 0.9 and 1.33
ppm, respectively, represent
typical long-chain lipids
(lipid/lactate). NAA and Cr are
barely detectable. A small Cho
peak, C, is seen to resonate at
3.2 ppm. (B; TE = 144ms) Long
TE MRS depicts persistence of
predominant lipid peak at 1.33
ppm.
Dx- Multiple tuberculoma

53. A 14 Y M WITH REFRACTORY CPS PLANNED
FOR SURGERY
•Conventional MRI
revealed no apparent
abnormality.
•MRS of Left anterior
hippocampus showed
smaller NAA peak (33%
less) compared to Right
indicating a left temporal
seizure focus
LeftRight

54.  MRS in hippocampal sclerosis
Short TE (35msec) spectra at 3T obtained in the left and right hippocampal
formation from a patient with right HS using single-voxel technique.
The decreased NAA signal and the increased mI at the affected region (A) are
shown when compared with the contralateral normal hippocampal formation

55. FUC OF A 48YR F WITH PROVEN GLIOBLASTOMA
MULTIFORME TREATED WITH SURGERY,
EXTERNAL BEAM RADIATION AND
INTERSTITIAL BRACHYTHERAPY.
A, Axial T1-weighted MR image
reveals enhancement of a right
frontal lobe/insular lesion that has
both solid and cavitary components.
The spectroscopy voxel includes
the medial margin of enhancement.
DDx- ?Recurrent tumor,
?Radiation necrosis
B, MR spectrum shows a prominent
lipid/lactate peak with minimal
residual Cho and Cr; NAA is
absent.
Dx -radiation necrosis
Diagnosis was confirmed at
resection. This patient had
subsequent follow-up spectroscopy
studies at 1, 3, and 4 months that
were unchanged (not shown).
Lip
Lac
Cho Cr NAA

56. 76 YRS MALE PRESENTED WITH RECENT MEMORY LOSS
•T1W image shows reduction in
the volume of the hippocampus.
•Proton MRS in hippocampal
region shows
MI peak, decreased NAA and
elevated MI/Cr ratio
•Dx - Alzheimer’s Disease

57.  Canavan disease, or spongiform leukodystrophy, results froma
deficiency of aspartocylase, an enzyme that hydrolyzes NAAto
acetate and aspartate.
In its absence, NAA accumulates in the brain.
MRS is diagnostic for this condition because the abnormally
high NAA peak is almost exclusively seen in Canavan disease.

58.  Patient with known diagnosis of MELAS with new onset of visual
symptoms. (Mitochondrial encephalomyopathy, lactic acidosis and stroke-like
episodes) presenting
(A) 1.5T brain MRI demonstrates areas of T2 hyperintensity and
(B) abnormal restricted diffusion, likely related to stroke-like areas of cytotoxic
edema.
(C)MR spectroscopy (TE=144 ms) from the right occipital abnormality shows
an inverted doublet at 1.3 ppm (arrows) consistent with a lactate peak.

59. MRS IN OTHER CONDITIONS
 Ischemic stroke- appearance of lactate peak
within minutes of ischemia. In chronic phase NAA
is suppressed
 AIDS dementia- increased MI and Gln detected.
MRS may help in detection of subclinical disease,
opportunistic infections and monitoring ART
 Multiple sclerosis- Increased Cho due to active
demylination. Lipid and Lac may also rise.
Presence of MI suggests severe demylination

60. FUNCTIONAL MRS
 It is a promising new technique still in
research phase
 Fast spectroscopic imaging technique is used to
detect transient rise in metabolites during
language or visual tasks
 Increase in Lac and Cr have been noted in left
temporal lobe during language task
 May complement fMRI and PET

61. 7 MONTH INFANT WITH DELAYED MILESTONES & SPASTICITY
 T 1W– diffuse hypointensity
of supratentorial white
matter.
 T2W -diffuse hyperintensity
of supratentorial white
matter
 MRS show markedly
raised NAA peak as
compared to control
subject.
 Dx – Canavan’s disease.

62. 5 YRS CHILD WITH SEIZURES & 2
 A – T 2 W- hyperintenseleft occipital region.
 B- MRS obtained from rt & lt occipital cortices.
• -inverted doublet lactate peak from rt occipital cortex
at 1.3
• ppm
• -reduced all peaks from old lt lesion.
 Dx – MELAS
STROKE LIKE EPISODES

63. ALZHEIMER’S DISEASE
•T1W image shows reduction in the volume
of the hippocampus of the patient with AD
•Proton MRS in hippocampal region shows
MI peak,decreased NAA and elevated MI/Cr ratio

64. PATIE
NT
WITH REFRACTORY CPS PLANNED FOR SURGERY
•Conventional MRI revealed
no apparent abnormality.
•MRS of Left anterior
hippocampus showed
smaller NAA peak (33% less)
compared to Right indicating
a left temporal seizure focus
LeftRight

65. LOCALISED 1H-MR SPECTROSCOPY FOR METABOLIC CHARACTERISATION
OF DIFFUSE AND FOCAL BRAIN LESIONS IN PATIENTS INFECTED WITH HIV I
L SIMONEA ET AL
 A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV
diagnostic
groups in comparison with neurological controls (p<0.003),
 The NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV
encephalopathies (p<0.02) and toxoplasmosis (p<0.05).
 HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant
increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03)
 The presence of a lipid signal was more frequent in lymphomas (71%) than in
other HIV groups
CONCLUSION 1H-MRS shows a high sensitivity in detecting brain involvement in HIV
related diseases, but a poor specificity in differential diagnosis of HIV brain

66. OTHER CONDITIONS:
 Hepatic encephalopathy: increased glutamate,
decreased myoinositol
 Phenylketonuria: increased Phenylalanine peak at
7.3ppm
 Parkinson’s disease
 Motor neuron disease
 Psychiatric disease

67.  Proton magnetic resonance spectroscopy of the brain is useful
whenever biochemical or metabolic assessment may be
necessary, such as in differential diagnosis of focal brain
lesions (neoplastic and non-neoplastic diseases)
 Diagnosis , grading of tumors and response to treatment
 NAA marker of neuronal viability
 Tumors – increased Cho/Cr, Cho/NAA, lipid lactate, decreased
NAA/Cr
 Abscess: increased Cho/Cr, lactate, acetate, succinate peaks
 Demyelinating disease: slightly increased Cho/Cr, Cho/NAA,
lipid , decreased NAA/Cr
 It is non invasive, radiation free, time saving, cost effective,
very sensitive and specific

68. The MR spectra do not come labeled with
diagnoses. They require interpretation and
should always be correlated with the MR
images before making a final diagnosis

69. Conclusion
 There are two methods of proton magnetic resonance spectroscopy:
single voxel and
 multivoxel, with or without spectroscopic imaging.
 Single voxel proton magnetic resonance spectroscopy provides a rapid
biochemical
 profile of a localized volume within a region of interest that may be
determined, especially in brain studies.
 Spectroscopic imaging provides biochemical information about multiple,
small and contiguous volumes focalized on a particular region of interest
that may allow the mapping of metabolic tissue distribution.
 By using this method, the data obtained may be manipulated by computer
and superimposed on the image of an abnormality, thereby illustrating the
distribution of such metabolites within that area.

70. Interpretation of the spectroscopic curve
The spectrum represents radiofrequency signals emitted from
the proton nuclei of the different metabolites into the region of
interest. Specific metabolites always appear at the same
frequencies, expressed as parts per million, and are
represented on the horizontal axis of the graph. The vertical axis
shows the heights of the metabolite peaks, represented on an
arbitrary intensity scale

71. • Bradley’s Neurology in clinical
practice 7th edition
• Neuroradiology in clinical Practice : 1st
edition
• Clinical MR Neuroimaging :
Diffusion, Perfusion &
Spectroscopy :
• MRI Brain and spine : Scott W.
Atlas: 4th edition
Reference

72. Thank You
Nitish Virmani
Lecturer
Department of Radio-Imaging Technology
Faculty of Allied Health Sciences
SGT University
Email- nitishvirmani18@gmail.com