MAGNETIC RESONANCE

SPECTROSCOPY

(MRS)

DR .Anurag Kumar Singh

Introduction

Physics

Interpretation

Indications

Cases

Summary

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.

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).

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.

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.

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.

NORMAL MRS CHOLINE NAA CREATINE

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

MULTI VOXEL MRS

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,

PRINCIPLE METABOLITESMetabolite 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

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

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

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

MalignancyDemyelinating

disease Pyogenic

abscess

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

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

A 50 yr M with fever, headache and Lt hemiparesisB, 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

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

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

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

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

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

MRS in hippocampal sclerosis

Short TE (35msec) spectra at 3T obtained in the left and right hippocampalformation 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

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

LacNAACho Cr

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

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.

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 cytotoxicedema.(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.

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

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

7 MONTH INFANT WITH DELAYED MILESTONES & SPASTICITY

T 1W– diffuse hypointensityof supratentorial white matter.

T2W -diffuse hyperintensityof supratentorial white matter

MRS show markedly raised NAA peak as compared to control subject.

Dx – Canavan’s disease.

5 YRS CHILD WITH SEIZURES & 2 STROKE LIKE EPISODES

A – T 2 W- hyperintense left occipital region.

B- MRS obtained from rt & ltoccipital cortices.

-inverted doublet lactate peak

from rt occipital cortex at 1.3 ppm

-reduced all peaks from old lt

lesion.

Dx – MELAS

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

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

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.

J Neurol Neurosurg Psychiatry 1998;64:516-523 doi:10.1136/jnnp.64.4.516

OTHER CONDITIONS:

Hepatic encephalopathy: increased glutamate,

decreased myoinositol

Phenylketonuria: increased Phenylalanine peak at

7.3ppm

Parkinson’s disease

Motor neuron disease

Psychiatric disease

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

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

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.

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.

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 neuroectodermaltumors (PNET) from other common brain tumors in pediatric patients as taurine concentration was significantly elevated in PNETs compared to other tumors

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

EFFECT OF TE ON THE PEAKS

__________

TE 35ms

___________

___________

TE 144ms

__________

Normal spectral data obtained at intermediate echo-time by single-voxel 1H magnetic resonance spectroscopy of the cerebellar vermisusing 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

CASE 9- CANAVAN’S DISEASE

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.

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