Spectroscopy (January, 2010)

Magnetic ResonanceMagnetic ResonanceSpectroscopySpectroscopy

(MRS)(MRS)

Basic PrinciplesBasic PrinciplesSingle Voxel TechniquesSingle Voxel Techniques

Chemical Shift Imaging (CSI)Chemical Shift Imaging (CSI)Water SuppressionWater Suppression

Clinical ApplicationsClinical Applications

MR SpectroscopyMR Spectroscopy• Magnetic Resonance Spectroscopy (MRS) Magnetic Resonance Spectroscopy (MRS)

provides a non-invasive method of studying provides a non-invasive method of studying metabolism in vivo. metabolism in vivo.

• The tissue’s chemical environment The tissue’s chemical environment determines the frequency of a “metabolite determines the frequency of a “metabolite peak” in an MRS “spectrum”.peak” in an MRS “spectrum”.

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Spectrum: graph of amount of Spectrum: graph of amount of metabolites versus frequencymetabolites versus frequency

NAA Peak

Choline Peak

Creatine Peak

MR SpectroscopyMR Spectroscopy• Candidates for MRS include:Candidates for MRS include:

• 11H, H, 3131P, P, 1313C, C, 2323Na, Na, 77Li, Li, 1919F, F, 1414N, N, 1515N, N, 1717O, O, 3939KK

• The most commonly studied nuclei are The most commonly studied nuclei are 11H H and and 3131PP

• This lecture is focused on Proton (This lecture is focused on Proton (11H) H) SpectroscopySpectroscopy

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MR SpectroscopyMR Spectroscopy• Imaging Voxel:Imaging Voxel:

– 1 – 5 mm1 – 5 mm33

– Signal from water (and fat)Signal from water (and fat)

– 111 Molar concentrations111 Molar concentrations

• Spectro Voxel:Spectro Voxel:

– 1 – 8 cm1 – 8 cm33

– Signal from metabolitesSignal from metabolites

– 1 – 10 milliMolar concentrations1 – 10 milliMolar concentrations

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Proton SpectroscopyProton Spectroscopy

• Electrons have HUGE magnetic momentsElectrons have HUGE magnetic moments– ~700 times the proton magnetic moment~700 times the proton magnetic moment

• The static magnetic BThe static magnetic B00 field “seen” by a nucleus field “seen” by a nucleus in a molecule is shielded by the covalent electron in a molecule is shielded by the covalent electron structure surrounding the nucleus. structure surrounding the nucleus.

• The electron cloud produces a small change in The electron cloud produces a small change in the magnetic field around nuclei in molecules.the magnetic field around nuclei in molecules.

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• Electrons in water molecules (HElectrons in water molecules (H22O) create a O) create a different local magnetic field than electrons in fat different local magnetic field than electrons in fat molecules (CHmolecules (CH22))

• This is “Chemical Shift” which we see in clinical This is “Chemical Shift” which we see in clinical images.images.

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9http://www.steve.gb.com/science/spectroscopy.htmlhttp://www.steve.gb.com/science/spectroscopy.html

Ethanol spectrumEthanol spectrum

OHOH CHCH22 CHCH33

Proton SpectroscopyProton Spectroscopy• Chemical shiftsChemical shifts in in HzHz are are dependentdependent on on

the strength of the applied field Bthe strength of the applied field B00 – Chemical shift between water and fat:Chemical shift between water and fat:

• 220 Hz at 1.5T220 Hz at 1.5T

• 440 Hz at 3T440 Hz at 3T

• Chemical shiftsChemical shifts in in ppmppm are are independentindependent of the strength of the applied field Bof the strength of the applied field B00

– Chemical shift between water and fat:Chemical shift between water and fat:• 3.44 ppm at 1.5T3.44 ppm at 1.5T

• 3.44 pm at 3T3.44 pm at 3T 10


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Single voxel spectroscopy (Single voxel spectroscopy (SVSSVS))•Point-RESolved Spectroscopy (Point-RESolved Spectroscopy (PRESSPRESS))•Stimulated echo acquisition method (Stimulated echo acquisition method (STEAMSTEAM))

Chemical shift imaging (Chemical shift imaging (CSICSI).).•2D-CSI2D-CSI•3D-CSI3D-CSI

Essential: suppress the water signal, CHEmical-Shift-Essential: suppress the water signal, CHEmical-Shift-Selective (Selective (CHESSCHESS) pulses) pulses


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•The concentration of pure water is 55.6 M for The concentration of pure water is 55.6 M for HH22O or 111 M for O or 111 M for 11H.H.•The water concentration in the brain is about The water concentration in the brain is about 70% or 36 M. 70% or 36 M. •In vivo In vivo 11H spectroscopy requires water H spectroscopy requires water suppression because the 36 M water signal suppression because the 36 M water signal overpowers the 1-10 mM signal of the overpowers the 1-10 mM signal of the metabolites.metabolites.


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This figure demonstrates the importance of suppressing the This figure demonstrates the importance of suppressing the water signal. The metabolites of interest have a signal water signal. The metabolites of interest have a signal one hundred times smaller than that of the water peak, one hundred times smaller than that of the water peak, and without water suppression would be poorly resolvedand without water suppression would be poorly resolved

© Scott & White 2004© Scott & White 2004

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Proton Spectroscopy (SVS with PRESS)Proton Spectroscopy (SVS with PRESS)

Basic diagram of SVS with spin echo (ref #1)Basic diagram of SVS with spin echo (ref #1)• Water-suppressionWater-suppression• The 90° pulse excites a slice. The 90° pulse excites a slice. • The first 180° pulse refocuses the transverse The first 180° pulse refocuses the transverse

magnetization in a row of tissue within the magnetization in a row of tissue within the slice. slice.

• The second 180° pulse refocuses the The second 180° pulse refocuses the magnetization within a column of the row, magnetization within a column of the row, leaving a single voxel. leaving a single voxel.

• Then, the signal represents a combination of Then, the signal represents a combination of spins in that voxel precessing at slightly spins in that voxel precessing at slightly different frequencies (function of time).different frequencies (function of time).

• Fourier transform of signal Fourier transform of signal number of number of spins at a given frequency in a voxel spins at a given frequency in a voxel (function of frequency).(function of frequency).


For one acquisition scheme– Point RESolved Spectroscopy For one acquisition scheme– Point RESolved Spectroscopy (PRESS)(PRESS)

Proton Spectroscopy Proton Spectroscopy (SVS with PRESS)(SVS with PRESS)

The effect of echo time in SE single voxel spectroscopy (SVS).The effect of echo time in SE single voxel spectroscopy (SVS).

Left: TE=30ms; Right: TE=144 ms. Glx (glutamine) and myoinositol (mI) have Left: TE=30ms; Right: TE=144 ms. Glx (glutamine) and myoinositol (mI) have short Tshort T22 values and are not visible on long TE spectra. values and are not visible on long TE spectra.

15© Scott & White 2004© Scott & White 2004

Proton Spectroscopy Proton Spectroscopy (SVS with PRESS)(SVS with PRESS)

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Major healthy brain metabolite peaks:Major healthy brain metabolite peaks:

short TE spectra (add’l peaks): 4) myoinositol (mI) at 3.56 ppm, 5) glutamine short TE spectra (add’l peaks): 4) myoinositol (mI) at 3.56 ppm, 5) glutamine and glutamate (Glx) between 2.05-2.5 ppm and 3.65-3.8 ppm, and 6) and glutamate (Glx) between 2.05-2.5 ppm and 3.65-3.8 ppm, and 6) glucose at 3.43 ppm.glucose at 3.43 ppm.

long TE spectra: 1) N-acetylaspartate (NAA) at 2.02 ppm, 2) choline (Cho) at long TE spectra: 1) N-acetylaspartate (NAA) at 2.02 ppm, 2) choline (Cho) at 3.20 ppm, and 3) creatine (Cr) at 3.02 ppm and 3.9 ppm. 3.20 ppm, and 3) creatine (Cr) at 3.02 ppm and 3.9 ppm.


Proton Spectroscopy Proton Spectroscopy (SVS with STEAM)(SVS with STEAM)

Basic diagram of SVS with STEAM: Basic diagram of SVS with STEAM:

•Water-suppressionWater-suppression•The 90° pulse excites a slice. The 90° pulse excites a slice. •A second 90° pulse refocuses the transverse A second 90° pulse refocuses the transverse magnetization in a row of tissue within the magnetization in a row of tissue within the slice. slice.

•A third 90° pulse refocuses the magnetization A third 90° pulse refocuses the magnetization within a column of the row, leaving a single within a column of the row, leaving a single voxel.voxel.

Negative to STEAM: rephasing only about Negative to STEAM: rephasing only about 50% of the original generated transverse 50% of the original generated transverse magnetization (low SNR). magnetization (low SNR). ~ (sort of ) Positive to STEAM: shorter echo ~ (sort of ) Positive to STEAM: shorter echo times than PRESS sequence.times than PRESS sequence.


Multivoxel Spectroscopy Multivoxel Spectroscopy (Chemical Shift Imaging)(Chemical Shift Imaging)

Phase encoding gradients can be utilized, as in Phase encoding gradients can be utilized, as in imaging, in order to encode spatial information.imaging, in order to encode spatial information.

Figure 4 illustrates a simple 2D chemical shift Figure 4 illustrates a simple 2D chemical shift imaging (CSI) acquisition scheme. imaging (CSI) acquisition scheme.

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Figure 4Figure 4


Multivoxel Spectroscopy Multivoxel Spectroscopy (Chemical Shift Imaging)(Chemical Shift Imaging)

Figure 5 illustrates the imaging setup for a 2D CSI Figure 5 illustrates the imaging setup for a 2D CSI acquisition. acquisition.

A single slice is defined through the area of interest, A single slice is defined through the area of interest, and then a box is specified within this (white lines). and then a box is specified within this (white lines).

Spectra will then be generated for all voxels within the Spectra will then be generated for all voxels within the box. box.

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Figure 5Figure 5

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This figure presents the spectra for a low grade brainstem glioma. This figure presents the spectra for a low grade brainstem glioma. SE CSI acquisition: two spectra (TE=30 ms--second column, and SE CSI acquisition: two spectra (TE=30 ms--second column, and 144 ms--third column). The first column shows the voxel 144 ms--third column). The first column shows the voxel corresponding to the spectra on the same row. Rows: 1st=lesion corresponding to the spectra on the same row. Rows: 1st=lesion spectra, 2nd= normal brain spectra.spectra, 2nd= normal brain spectra.


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The lesion spectra demonstrate decreased The lesion spectra demonstrate decreased NAANAA (a marker of (a marker of neuronal integrity) and increased neuronal integrity) and increased cholinecholine (a marker of myelin (a marker of myelin breakdown). The short TE spectrum demonstrates elevated breakdown). The short TE spectrum demonstrates elevated myo-myo-inositolinositol (a marker of glial cells). (a marker of glial cells).

Figure 6 (next slide) presents a color-coded choline metabolite Figure 6 (next slide) presents a color-coded choline metabolite map.map.


Figure 5Figure 5

Figure 6Figure 623

Multivoxel SpectroscopyMultivoxel Spectroscopy


Choline Map

• The clinical utility of the brain spectrum rests The clinical utility of the brain spectrum rests upon 2 important properties:upon 2 important properties:– The nature and concentration of brain chemicals The nature and concentration of brain chemicals

identified is remarkably constant—identified is remarkably constant—• A “normal” brain spectrum is readily recognizedA “normal” brain spectrum is readily recognized

– The particular neurochemicals concerned are of The particular neurochemicals concerned are of clinical relevance in healthy and diseased brain.clinical relevance in healthy and diseased brain.

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Brain SpectroscopyBrain Spectroscopy

25© 2007 by© 2007 by ProScanProScan ImagingImaging

26Single Voxel Prescription/positioningSingle Voxel Prescription/positioning

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Single Voxel Spectra from PhantomSingle Voxel Spectra from PhantomOn Left: STEAM 35 TE On Right: PRESS 35 TEOn Left: STEAM 35 TE On Right: PRESS 35 TE

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Single Voxel Spectra PRESS TE 144Single Voxel Spectra PRESS TE 144

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Single Voxel Spectra PRESS TE 288Single Voxel Spectra PRESS TE 288


• Voxel placementVoxel placement30

• SpectrumSpectrum


• Voxel placementVoxel placement• With saturation bandsWith saturation bands

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• Spectrum from GBMSpectrum from GBM• Elevated choline, lactateElevated choline, lactate

• decreased NAAdecreased NAA

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2D CSI of phantom --processed result2D CSI of phantom --processed result

Mutlivoxel spectroscopyMutlivoxel spectroscopy

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3D CSI from 3D CSI from phantom—phantom—processed result processed result with composite with composite metabolite mapmetabolite map

Spectroscopy of the ProstateSpectroscopy of the Prostate

• Prostate cancer is associated with Prostate cancer is associated with proportionately proportionately lowerlower levels oflevels of citratecitrate and and higher levels of choline and creatine than higher levels of choline and creatine than are seen in benign prostatic hyperplasia are seen in benign prostatic hyperplasia (BPH) or in normal prostate tissue.(BPH) or in normal prostate tissue.

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© Reviews in Urology 2006© Reviews in Urology 2006

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greatly reduced citrategreatly reduced citrate, elevated choline , elevated choline prostate cancer prostate cancer

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The diagnostic value of MR The diagnostic value of MR spectroscopy is typically based on the spectroscopy is typically based on the detection of elevated levels of choline detection of elevated levels of choline compounds, which are a marker of compounds, which are a marker of active tumors.active tumors.

Spectroscopy of the BreastSpectroscopy of the Breast

© Radiology 2007© Radiology 2007

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(From previous slide) (From previous slide) Palpable mammographically detected and Palpable mammographically detected and biopsy-proved invasive lobular carcinoma biopsy-proved invasive lobular carcinoma in left breast of 56-year-old woman. in left breast of 56-year-old woman. This is a true-positive finding. This is a true-positive finding.



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Suspicious nonmass lesion detected at Suspicious nonmass lesion detected at screening MR imaging in 38-year-old screening MR imaging in 38-year-old woman withwoman withBRCA-1 BRCA-1 gene who was imaged at day 11 of gene who was imaged at day 11 of her menstrual cycle. her menstrual cycle. This is a true-negative finding.This is a true-negative finding.



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elevatedelevated levels of levels of cholinecholine compounds compounds marker marker of active tumors.of active tumors.


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Spectroscopy at 3T vs 1.5TSpectroscopy at 3T vs 1.5T

1.5T1.5T3T3T

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References:References:

• Proton magnetic resonance spectroscopy in Proton magnetic resonance spectroscopy in the brain: Report of AAPM MR Task group the brain: Report of AAPM MR Task group #9.#9. Drost, D.J., et al., Med Phys 29(9) Drost, D.J., et al., Med Phys 29(9) Sept 2002.Sept 2002.

• Questions and Answers in Magnetic Questions and Answers in Magnetic Resonance ImagingResonance Imaging (2 (2ndnd Edition). Elster, Edition). Elster, A.D. and Burdette, J. H. Mosby, St. Louis A.D. and Burdette, J. H. Mosby, St. Louis 20012001

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• Medical Magnetic Resonance Imaging and Medical Magnetic Resonance Imaging and Spectroscopy.Spectroscopy. Edited by Budinger Edited by Budinger &Margulis. Society of Magnetic &Margulis. Society of Magnetic Resonance in Medicine 1986Resonance in Medicine 1986

• Clinical Applications of MR SpectroscopyClinical Applications of MR Spectroscopy

Edited by Mukherji Wiley & Sons, New Edited by Mukherji Wiley & Sons, New York 1998York 1998

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• MRI from Picture to ProtonMRI from Picture to Proton D.W. D.W. McRobbie et al. Cambridge University McRobbie et al. Cambridge University Press 2003Press 2003

• Magnetic Resonance Spectroscopy of Magnetic Resonance Spectroscopy of Neurological DiseasesNeurological Diseases E. R. Danielsen E. R. Danielsen Marcel Dekker, Inc. New York 1998.Marcel Dekker, Inc. New York 1998.

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• © © Reviews in Urology 2006Reviews in Urology 2006

Carroll, et. al., Carroll, et. al., Magnetic Resonance Magnetic Resonance Imaging and Imaging and Spectroscopy of Prostate CancerSpectroscopy of Prostate Cancer;; REVIEWS IN REVIEWS IN UROLOGY UROLOGY Vol. 8 Suppl. 1 2006Vol. 8 Suppl. 1 2006

• © © Scott & White 2004Scott & White 2004

Runge,VM, Nitz,WR, et al. Runge,VM, Nitz,WR, et al. The Physics of Clinical MR, for The Physics of Clinical MR, for

Neuroradiology, Taught Through Images.Neuroradiology, Taught Through Images. • ©© Radiology 2007 Radiology 2007

Bartella, et al., Bartella, et al., Enhancing Nonmass Lesions in the Breast: Enhancing Nonmass Lesions in the Breast: Evaluation with Proton (1H) MR SpectroscopyEvaluation with Proton (1H) MR Spectroscopy Radiology Radiology Volume 245 (1) October 2007Volume 245 (1) October 2007

• © 2007 by ProScan Imaging© 2007 by ProScan ImagingTHE MRI MENTOR, Volume 1, Number 10 – October 8, THE MRI MENTOR, Volume 1, Number 10 – October 8, 20072007


Spectroscopy (January, 2010)

Technology

water peak

water signalsuppression

spectroscopy point

waterh spectroscopy

water molecules helectrons

water molecules h22o

aboutthe water concentration

proton magnetic moment