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Applications of Clinical Magnetic

Resonance Spectroscopy

Jeffry R. Alger, PhD


Department of Neurology
Department of Radiology
University of California, Los Angeles
jralger@ucla.edu

ESMP October 2008


Outline
• Principles of MRS

• MRS signals

• Clinical Applications
Principles of Magnetic
Resonance Spectroscopy (MRS)
Biomedical Magnetic Resonance

• MRI
– Imaging water and sometimes lipid protons

• MRS
– Imaging all other chemicals including lipids

• Fundamental physics of signal detection


is essentially identical for MRI and MRS
Clinical MRS Applications
• Evaluation of brain metabolites

• Application to other body regions is


growing
– breast
– prostate

• Evaluation of cancer
Biomedical MRS signals
• Arise from stable (not radioactive) nuclei

• Endogeneous nuclei
– 1H, 31P, 23Na, 13C

• Exogeneously supplied nuclei


– 13C, 7Li, 19F
1H-MRS

• Most frequently used for routine clinical


MRS studies

• Focus of this presentation


Signal Frequency Measurement
• Frequency measurement is fundamental to
MRS

• Unique nuclear isotopes are distinguished


by their unique characteristic radio
frequencies

• Chemical structure imposes a “fine


structure” allowing the detection of
individual chemicals
1 part per
million (ppm)

13C 31P 19F 1H

16 26 60 63
Radio frequency (MHz) using a 1.5 Tesla magnetic field
MRS Localization Methods
• Single Voxel MRS • Spectroscopic Imaging (MRSI)
– Obtains single spectrum at – Obtains multiple spectra
• Better spatial resolution & extent
user-defined location • Enables image formation
– Simple – More complex to acquire
• Longer acquisition times
• Largely automated
– More complex to analyze
• Good SNR and spectral • Lower SNR
quality • more spectral distortions
• more data
– Limited spatial information

NAA Creatine Choline


4.0 3.0 2.0 1.0

A.A. Maudsley
MRS Localization Techniques
• Single voxel MRS
– STEAM
– PROBE
– PROBE-SV (General Electric)
– SVS (Siemens)

• Magnetic Resonance Spectroscopic


Imaging (MRSI)
– Chemical Shift Imaging (CSI)
– Spectroscopic Imaging (SI)
– PROBE-MV (General Electric)
– CSI (Siemens)
– “Multivoxel” MRS
1H-MRS Signals
1H-MRS Signals
• Signals arise mostly from intracellular molecules

• Signals arise from small molecules involved in


metabolism
– MRS is a “metabolite imaging” technique

• Signal-to-noise ratio limits the number of


detectable metabolites

• Overlap between signals limits the number of


detectable metabolites
Brain 1HMRS Spectrum
Key Signals
Water (suppressed )
Choline(s)
Creatine
NAA

Lactate &
Lipids
N-acetylaspartate (NAA)
Present in neurons including axons
Used to assess for disruption of neuronal cytoarchitecture

H
- OC CH2 C CO2-
2

C O

CH3
T2w MRI NAA

Spectroscopic Imaging of a newly


diagnosed oligodendroglioma
Choline
Generated by a group of metabolites involved in membrane metabolism
Often said to relate to “membrane turnover”
Often elevated in primary brain tumors

CH3

RO CH2 CH2 N CH3

CH3
T2w MRI NAA Choline

Spectroscopic Imaging of a newly diagnosed


oligodendroglioma
MRS of Breast Cancer
Cecil & Lenkenski

• Choline signal is
elevated in breast
tumors

• Helpful in evaluating
whether tumor is
– Benign
– Malignant

• Lipid signals are


complications
MRS of Prostate Cancer
Kurhanewicz et al

• Choline signal is
elevated in prostate
tumors

• Helpful in evaluating
whether tumor is
– Benign
– Malignant

• Lipid signals are


complications
Creatine
Generated by the sum of creatine and phosphocreatine (i.e total
creatine)
Often used as an internal standard

H CH3

- OP N C N CH2 CO2-
3

NH
Lactic acid
Produced by anaerobic metabolism
Glycolytic metabolism in tumors
Ischemic penumbra in stroke

O
- OC C CH3
2
Lactate Signals
• Marker of anaerobic metabolism

• Often present in cystic cavities

• Bad prognostic feature


Lactate
Postconstrast MRI
Spectroscopic
Image

ppm
3 2 1 0
Clinical Applications
Brain Cancer
MRS & Brain Cancer
• Initial diagnosis without surgery
– MRS can not be used to diagnose the type of tumor
– MRS can sometimes be used for differential
diagnosis
• Tumor vs infarction
• Tumor vs multiple sclerosis
• Tumor vs infection

• Surgical or radiation therapy planning

• Diagnosis of recurrent tumor following


radiation therapy
Diagnosis of Brain Tumor with MRS
Howe et al Magnetic Resonance in Medicine 2003;49:223-232

• Some unique types of


tumors produce unique
MRS patterns

• MRS patterns of unique


tumors can overlap

• No single signal is
“diagnostic”
Epilepsy
• MRS can be used to help lateralize seizure focus

• Typically in temporal lobe epilepsy

• NAA decreased in focus

• NAA decrease usually attributed to sclerosis

• Lactate may be increased in focus


MRS - “Clinical” Uses
• Diagnosis and Management of Individual
Patients
– Cancer
• Brain
• Breast
• Prostate
• Head and Neck
– Epilepsy
– Metabolic Diseases
– Brain Trauma

• Clinical Research
– Dementia
– Mental Disorders
Summary
• MRS detects signals from a limited number of
brain chemicals in situ without the use of
radiation

• Single voxel and spectroscopic imaging


techniques are available as FDA-cleared
packages on several manufacturers’ MRI
scanners

• MRS is helpful in several clinical contexts

• Clinical research studies are teaching us how to


exploit the MRS features for clinical purposes

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