Magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that measures metabolite levels in tissues. It works by detecting signals from atomic nuclei such as hydrogen placed in a strong magnetic field. MRS is useful for evaluating brain tumors, infections, demyelinating diseases, and neurodegenerative conditions. It provides diagnostic information by analyzing peak levels of metabolites including NAA, creatine, choline, and lactate. MRS can help distinguish tumors from other lesions, detect radiation necrosis, and monitor treatment response. It is also used to diagnose inborn errors of metabolism and mitochondrial disorders.

1. MAGNETIC RESONANCE
SPECTROSCOPY
(MRS)
DR .Anurag Kumar Singh

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.  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.

6. MRS TECHNIQUES
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
Single Volume MRS
Multivolume MRS- multiple adjacent volume over a large region of interest
can be assessed in a single measurement. Acquisition time is 6-12 min.

7. 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.

8. NORMAL MRS CHOLINE NAA CREATINE

9.  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 differentiate them
from lipids.
(B) Short TE demonstrates peaks attributable to more metabolites,
including lipids, glutamine and glutamate, and myo-inositol

10. MULTI VOXEL MRS

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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20.  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

21. 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

22. 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

24. 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

25.  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

26. 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
NAACho Cr

27. 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

28.  Canavan disease, or spongiform leukodystrophy, results from a
deficiency of aspartocylase, an enzyme that hydrolyzes NAA to
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.

29.  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.

30. 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

31. 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

32. 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.

33. 5 YRS CHILD WITH SEIZURES & 2 STROKE LIKE EPISODES
 A – T 2 W- hyperintense left
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

34. 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

35. PATIENT 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

36. 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 lesions.

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

38.  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

39.  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

40.  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);
 brain lesions in patients with acquired immunodeficiency syndrome;
 Diagnosis of dementiaand other degenerative diseases;
 follow-up radiation therapy for patients with brain neoplasms;
 demyelinating diseases such as multiple sclerosis and
leukodystrophy;
 diagnosis and prognosis of brain ischemic and traumatic lesions
 assessment of epilepsy;
 biochemical alterations in hepatic encephalopathies;
 and neuropediatric affections such as brain tumors,
 inborn errors of metabolism and hypoxic encephalopathy.

41.  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.

42.  Short echo times are indicated for the study of
metabolic and diffuse diseases. By using long echo
times (more than 135 milliseconds), smaller
numbers of metabolites are detected, but with
better definition of peaks, thereby facilitating
graphic analysis. Long echo times are more used in
focal brain lesions.
 Quantitation of taurine (Tau) concentrations with
proton magnetic resonance spectroscopy improves
the differentiation of primitive neuroectodermal
tumors (PNET) from other common brain tumors in
pediatric patients as taurine concentration was
significantly elevated in PNETs compared to other
tumors

43.  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

44. EFFECT OF TE ON THE PEAKS
__________
TE 35ms
___________
___________
TE 144ms
__________

45.  Normal spectral data obtained at intermediate echo-time by single-
voxel 1H magnetic resonance spectroscopy of the cerebellar vermis
using a point-resolved spectroscopic sequence . X-axis, labelled in
parts per million (ppm). The amplitude of the resonances is measured
on the Y-axis using an arbitrary scale. The most prominent peak is N-
acetyl aspartate at 2.02ppm. Following from right to left: creatine (Cr)
at 3.02 (and 3.9) and choline (Cho) at 3.2

46. CASE 9- CANAVAN’S DISEASE

47.  Serial magnetic resonance imaging and spin-echo spectra recorded at
an echo time of 135 ms from an acute multiple sclerosis plaque. T2-
FLAIR images show an initial progressive lesion size increase followed
by a decrease over 1 year of follow up. 1H-MRS during the acute stage
shows the presence of Lac, a slight decrease in NAA, and an increase in
Cho. The longitudinal study demonstrates Lac disappearance at 3
months, persistent low levels of NAA, a progressive Cho increase during
the first weeks followed by partial recovery, and relatively stable Cr at all
time points.

48. THANK
YOU