2. BASIC PRINCIPLES
ā¢ Magnetic Resonance Spectroscopy (MRS) provides a measure of
brain chemistry.
ā¢ A non-invasive method of studying metabolism in vivo.
ā¢ The tissueās chemical environment determines the frequency of a
āmetabolite peakā in an MRS āspectrumā.
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3. BASIC PRINCIPLES
ā¢ The resonant frequencies of nuclei are at the lower end of
electromagnetic spectrum.
ā¢ Proton : ranges between 10 MHz at 0.3 T to 300 MHz on a 7T
magnet.
ā¢ Electrons have HUGE magnetic moments
ā¢ ~700 times the proton magnetic moment
4. SHIELD EFFECT & CHEMICAL SHIFT
ā¢ The static magnetic B0 field āseenā by a nucleus in a molecule is
shielded by the covalent electron structure surrounding the nucleus.
ā¢ The electron cloud produces a small change in the magnetic field
around nuclei in molecules.
ā¢ Electrons in water molecules (H2O) create a different local magnetic
field than electrons in fat molecules (CH2)
ā¢ This is āChemical Shiftā which we see in clinical images.
5. ā¢ Chemical shift Ī“ is usually expressed in parts per million (ppm) by
frequency,
ā¢ it is calculated from:
ā¢ = difference between a resonance freq & that of a reference
substance/ operating freq of the spectrometer
ā¢ Since the numerator is usually in hertz, and the denominator in
megahertz, delta is expressed in ppm.
ā¢ The detected frequencies (in Hz) for 1H, 13C, and 29Si nuclei are
usually referenced against TMS (tetramethylsilane) or DSS, which is
assigned the chemical shift of zero. Other standard materials are used
for setting the chemical shift for other nuclei.
6. TYPES
ā¢ A)
ā¢ 1 H (Proton)
ā¢ 31 P (Phosphorus)
ā¢ 23 Na (Sodium)
ā¢ B)
ā¢ Single Voxel
ā¢ Multi voxel (Chemical Shift Imaging)
7. TECHNIQUE (PROTON SPECTROSCOPY)
ā¢ After the nuclei have been exposed to a uniform magnetic field, they
receive a 90 degree RF pulse.
ā¢ The nuclei rotates from the z-axis to x-axis.
ā¢ When this pulse is turned off, the nuclei return to their position in z-
axis.
ā¢ The time it takes them to return is governed by their relaxation times.
ā¢ The receiving coil detects the voltage variations at many points in time
during this period . This voltage variation is termed as āfree induction
decayā.
ā¢ This may be plotted as an exponential decay function ( intensity Vs
time) to yield time domain information (ie, relaxation times).
ā¢ Fourier transformation of this information yields information in the
frequency domain, namely, a plot of peaks at different Larmor
frequencies.
8. ā¢The parameters that characterize
each peak include its resonance
frequency, its height, and its width at
half-height.
ā¢The resonance frequency position of
each peak on the plot is dependent
on the chemical environment of that
nucleus and is usually expressed as
parts per million from the main
magnetic resonance frequency of the
system used (ie, chemical shift).
ā¢ The height (maximum peak
intensity) or the area under the peak
may be calculated and yield relative
measurements of the concentration of
protons.
9. ā¢ Fat is avoided by placing the voxel for MRS within the brain,
away from the fat in bone marrow and scalp.
ā¢ Water suppression is accomplished with either a CHESS
(CHEmical-Shift Selective ) or IR (Inversion Recovery)
technique.
ā¢ These suppression techniques are used with a STEAM or
PRESS pulse sequence acquisition.
ā¢ A Fourier transform is then applied to the data to separate the
signal into individual frequencies.
ā¢ Protons in different molecules resonate at slightly different
frequencies because the local electron cloud affects the
magnetic field experienced by the proton.
10. ā¢ As a general rule, the single voxel, short TE technique is used
to make the initial diagnosis as the SNR is high and all
metabolites are represented.
ā¢ Multi voxel. Long TE technique is used to further characterize
different regions of the mass and to assess brain parenchyma
adjacent to the mass.
ā¢ With a short TE of 30 msec, metabolites with both short and
long relaxation times are observed.
ā¢ With a long TE of 270 msec, only metabolite with a long T2 are
seen, producing a spectrum with mainly NAA, creatine &
choline.
11. SINGLE VOXEL SPECTROSCOPY
ā¢ In SVS, the signal is received of a volume limited to a single voxel.
This acquisition is fairly fast (1 to 3 minutes) and a spectrum is easily
obtained. It is performed in three steps:
ā¢ Suppression of the water signal: the quantity of hydrogen nuclei in
the water molecules in the human body is such that the water peak at
4.7 ppm ādrownsā and masks the spectroscopic signal from the other
metabolites.
ā¢ It is therefore vital to suppress the water peak to observe the
metabolites of interest.
ā¢ Selection of the voxel of interest
ā¢ Acquisition of the spectrum, for which two types of sequence are
available-
ā¢ (PRESS: Point-RESolved Spectroscopy,
ā¢ STEAM: STimulated Echo Acquisition Mode)
12. ā¢ Water signal suppression
ā¢ The most commonly used method to suppress the water peak is
CHESS (CHEmical Shift Selective).
ā¢ CHESS consists in applying three couples (90Ā° RF pulses +
dephasing gradients) in each spatial direction.
ā¢ The bandwidth of these RF pulses is narrow and centered on the
resonance frequency of the water peak in order to saturate the water
signal and preserve the signal from the other metabolites.
ā¢ Techniques applying a 180Ā° inversion pulse with adapted TI, like those
used in FLAIR and STIR sequences, can also be used to eliminate the
water signal (WEFT: Water Elimination Fourier Transform) or suppress
the fat signal in breast spectroscopy, for example.
ā¢ In practice, CHESS is more commonly used than WEFT.
13. This figure demonstrates the importance of suppressing the water
signal.
The metabolites of interest have a signal one hundred times smaller
than that of the water peak, and without water suppression would be
poorly resolved
14. ā¢ Principles of volume selection
ā¢ The analyzed volume is selected by a succession of three selective
radiofrequency pulses (accompanied by gradients) in the three
directions in space. These pulses determine three orthogonal planes
whose intersection corresponds to the volume studied. Only the signal
of this voxel will be recorded, by selecting only the echo resulting from
the series of three radiofrequency pulses.
ā¢
17. SVS WITH PRESS
THE EFFECT OF ECHO TIME IN SE SINGLE VOXEL SPECTROSCOPY (SVS).
TE=30ms TE=144 ms.
Glx (glutamine) and myoinositol (mI) have short T2 values and are not visible on
long TE spectra.
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19. MULTIVOXEL SPECTROSCOPY
(CHEMICAL SHIFT IMAGING)
ā¢ Metabolic imaging (CSI) consists in
recording the spectroscopic data for a
group of voxels, in slice(s) (2D) or by
volume (3D).
ā¢ It is based on a repetition of STEAM or
PRESS type sequences to which is added
spatial phase encoding.
ā¢ Phase encoding gradients can be
utilized, as in imaging, in order to encode
spatial information.
Figure illustrates a simple 2D chemical shift
imaging (CSI) acquisition scheme.
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20. MULTIVOXEL SPECTROSCOPY
(CHEMICAL SHIFT IMAGING)
A single slice is defined through the
area of interest, and then a box
is specified within this (white
lines).
Spectra will then be generated for
all voxels within the box.
20
This figure presents the spectra for a
low grade brainstem glioma.
SE CSI acquisition: two spectra
(TE=30 ms--second column, and 144
ms--third column).
The first column shows the voxel
corresponding to the spectra on the
same row.
Rows: 1st=lesion spectra, 2nd=
normal brain spectra.
23. METABOLITES, LOCATION, AND SIGNIFICANCE
ā¢ NAA (N-acetyl aspartate)
ā¢ The presence of NAA is attributable
to its N-acetyl methyl group, which
resonates at 2.0 ppm.
ā¢ is accepted as a neuronal marker,
and as such, its concentration will
decrease with any disease that
adversely affects neuronal integrity
ā¢ NAA is not present in tumors outside
the central nervous system
ā¢ Canavan disease is the only
disease in which NAA is increased.
ā¢ In normal spectra, NAA is the largest
peak.
24. ā¢ Cho (Choline)
ā¢ The peak for Cho occurs at 3.2 ppm .
ā¢ It contains contributions from
glycerophosphocholine, phosphocholine, and
phosphatidylcholine.
ā¢ and reflects total brain choline stores.
ā¢ Cho is a constituent of the phospholipid
metabolism of cell membranes and reflects
membrane turnover, and it is a precursor for
acetylcholine and phosphatidylcholine.
ā¢ The latter compound is used to build cell
membranes, whereas the former is a critical
neurotransmitter involved in memory,
cognition, and mood.
ā¢ Therefore, increased Cho probably reflects
increased membrane synthesis and/or an
increased number of cells.
25. ā¢ Creatine
ā¢ The peak for Cr is seen at 3.03 ppm and
contains contributions from Cr, Cr
phosphate, and, to a lesser degree, g-
aminobutyric acid, lysine, and glutathione.
ā¢ Cr probably plays a role in maintaining
energy-dependent systems in brain cells by
serving as a reserve for highenergy
phosphates and as a buffer in adenosine
triphosphate and adenosine diphosphate
reservoirs.
ā¢ Cr is increased in hypometabolic states and
decreased in hypermetabolic states.
ā¢ In normal spectra, Cr is located to the
immediate right of Cho and is the third-
highest peak.
ā¢ Because this peak remains fairly stable
even in face of disease, it may be used as a
control value.
26. ā¢ Lactate
ā¢ The lactate peak has a particular
configuration.
ā¢ It consists of two distinct, resonant peaks
called a ādoubletā and is caused by the
magnetic field interactions between
adjacent protons (J coupling).
ā¢ This lactate doublet occurs at 1.32 ppm.
ā¢ A second peak for lactate occurs at 4.1
ppm. Because this latter peak is very
close to the water, it is generally
suppressed.
ā¢ Normally, lactate levels in the brain are
low. The presence of lactate generally
indicates that the normal cellular oxidative
respiration mechanism is no longer in
effect, and that carbohydrate catabolism
is taking place
27. ā¢ Myoinositol
ā¢ Myoinositol is a metabolite involved in
hormone- sensitive neuro-reception and is
a possible precursor of glucuronic acid.
ā¢ The myoinositol peak occurs at 3.56 ppm.
ā¢ Decreased myoinositol content in the brain
has been associated with the protective
action of lithium in mania and the
development of diabetic neuropathy.
ā¢ The combination of elevated myoinositol
and decreased NAA may be seen in
patients with Alzheimer disease.
ā¢ The myoinositol peak is significant in
tissues outside the central nervous
system, for example , in head and neck
carcinomas.
28. ā¢ Lipids
ā¢ Membrane lipids in the brain have very short relaxation times and are
normally not observed unless very short TEs are used.
ā¢ The protons of lipids produce peaks at 0.8, 1.2, 1.5, and 6.0 ppm.
ā¢ These peaks comprise methyl, methylene, allelic, and the vinyl protons
ā¢ of unsaturated fatty acids.
ā¢ These metabolites may be increased in high-grade astrocytomas and
meningiomas and may reflect necrotic processes.
ā¢ Glutamine / GABA
ā¢ resonates at 2.2-2.4 ppm chemical shift
ā¢ Neurotransmitters, seen in excess in gliomas.
ā¢ Alanine
ā¢ resonates at 1.48 ppm chemical shift
ā¢ Seen in meningiomas.
30. CLINICAL APPLICATIONS
ā¢ Brain Tumors
ā¢ MRS can be used to determine the degree of malignancy. As a
general rule, as malignancy increases, NAA and creatine decrease,
and choline, lactate, and lipids increase.
ā¢ NAA decreases as tumor growth displaces or destroys neurons.
ā¢ Very malignant tumors have high metabolic activity and deplete the
energy stores, resulting in reduced creatine.
ā¢ Very hypercellular tumors with rapid growth elevate the choline levels.
ā¢ Lipids are found in necrotic portions of tumors, and lactate appears
when tumors outgrow their blood supply and start utilizing anaerobic
glycolysis.
ā¢ To get an accurate assessment of the tumor chemistry, the
spectroscopic voxel should be placed over an enhancing region of the
tumor, avoiding areas of necrosis, hemorrhage, calcification, or cysts.
31. A, Axial postcontrast MR T1-
weighted image shows the position
of a single voxel
B, Proton MR spectroscopy shows
patterns similar to those seen in
astrocytomas with elevated Cho and
low NAA. There is no obvious
lactate or alanine..
C, Axial precontrast MR T1-
weighted image shows location of
the volume of interest within a
frontobasal meningioma
(surgically proved).
D, Proton MR spectra show Cho (1),
Cr (2), and a peak (AāL) at 1.3 to
1.4 ppm, corresponding to alanine
and/or lactate. No definite NAA is
identified.
32. ā¢ Multi-voxel spectroscopy is best to detect infiltration of malignant cells
beyond the enhancing margins of tumors.
ā¢ Particularly in the case of cerebral glioma, elevated choline levels are
frequently detected in edematous regions of the brain outside the
enhancing mass.
ā¢ Finally, MRS can direct the surgeon to the most metabolically active
part of the tumor for biopsy to obtain accurate grading of the
malignancy.
34. Metastasis.
A, Single-volume proton MR spectroscopy in a solitary brain metastasis (proved small-cell
carcinoma). Note decreased NAA with respect to Cho and Cr, which appear elevated. Large
peaks (small and large asterisks) are probably combination of lactate and lipids.
B, Axial MR T2-weighted image (4000/ 93/1) shows the position of the voxel with respect to
the lesion. Note that the voxel is eccentric to the lesion to avoid skull and subcutaneous fat.
35. ā¢ A common clinical problem is distinguishing tumor recurrence
from radiation effects several months following surgery and
radiation therapy.
ā¢ Elevated choline is a marker for recurrent tumor. Radiation
change generally exhibits low NAA, creatine, and choline on
spectroscopy.
ā¢ If radiation necrosis is present, the spectrum may reveal
elevated lipids and lactate.
36. Recurrent tumor versus radiation necrosis.
Volume 21 shows low NAA, high Cho, and lactate (arrow) compatible with a recurrent tumor (later
proved by surgery).
Volume 24 shows no NAA, low Cho, and a ādeath peakā (combination of lactate and cellular
breakdown products).
Single-voxel proton MR spectroscopy in a surgically proved region of radiation-induced necrosis
shows large death peak.
37. ā¢ Cerebral Ischemia and
Infarction
ā¢ When the brain
becomes ischemic, it
switches to anaerobic
glycolysis and lactate
accumulates.
ā¢ Markedly elevated
lactate is the key
spectroscopic feature
of cerebral hypoxia
and ischemia.
ā¢ Choline is elevated,
and NAA and creatine
are reduced. If
cerebral infarction
ensues, lipids
increase.
The MRS demonstrates elevated lactate peak and
depressed NAA peak in the area of infarction,
indicating ongoing neuronal necrosis.
38. ā¢ Trauma
ā¢ MR spectroscopy is not routinely used in the acute setting of head
injuries.
ā¢ When the patient has stabilized, MRS is helpful to assess the degree
of neuronal injury and predict patient outcomes.
ā¢ Especially in the case of diffuse axonal injury, imaging often
underestimates the degree of brain damage. Clinical outcome
correlates inversely with the NAA/Cr ratio. The presence of any
lactate or lipid indicates a worse prognosis.
39. ā¢ Infectious Diseases
ā¢ Brain abscesses destroy or displace brain tissue, so NAA is not present.
ā¢ The voxel should include the abscess cavity to detect the breakdown
products of these lesions.
ā¢ Lactate, cytosolic acid, alanine, and acetate are characteristic
metabolites in bacterial abscesses
ā¢ Toxoplasmosis and tuberculomas show prominent peaks from lactate
and lipids.
ā¢ Choline is low or absent in toxoplasmosis, whereas it is elevated in
lymphoma, helping to distinguish the two.
ā¢ In patients with AIDS dementia complex, proton MR spectroscopy shows
a net reduction of NAA and decreases of NAA/Cho and NAA/Cr ratios.
ā¢ .Choline is the best marker for the white matter abnormalities, and the
extent of NAA depletion correlates directly with the degree of dementia.
ā¢ MRS is also very helpful in following patients and assessing the effects
of anti-viral therapies.
40. PEDIATRIC METABOLIC DISORDERS
ā¢ MRS has a very important role in diagnosing and monitoring patients with metabolic
disorders.This group includes a long list of diseases that affect the gray and white matter
to varying degrees.
41. HEPATIC ENCEPHALOPATHY
ā¢ The spectrum of hepatic encephalopathy is characterized by
markedly reduced myo-inositol.
ā¢ Choline is also reduced, and glutamine is increased.
ā¢ Similar metabolic changes are seen in Reye's syndrome, an acute
form of liver failure in infants.
ā¢ The metabolic changes of hepatic encephalopathy increase after
a TIPS shunt procedure, and they revert back to normal after
successful liver transplantation.
42. ALZHEIMER'S DISEASE
ā¢ Although MR spectroscopy is not highly sensitive for detecting early
Alzheimer's disease, as the disease progresses, the spectrum
becomes abnormal.
ā¢ Specifically, with advancing disease the NAA is reduced and myo-
inositol becomes elevated.
ā¢ Myo-inositol is also increased in Down's syndrome, a dementia that
presents in childhood and is pathogenetically similar to Alzheimer's
disease.
ā¢ On the other hand, myo-inositol is not elevated in other adult
dementia, so it is a helpful marker to distinguish Alzheimer's disease
from the other causes of dementia.
43. SPECTROSCOPY OF THE PROSTATE
ā¢ Prostate cancer is associated with proportionately lower levels of citrate
and higher levels of choline and creatine than are seen in benign prostatic
hyperplasia (BPH) or in normal prostate tissue.
45
44. 46
Spectroscopy of the Breast
The diagnostic value of MR spectroscopy is typically based on the detection of
elevated levels of choline compounds, which are a marker of active tumors.
(biopsy-proved invasive lobular carcinoma)
46. 31- PHOSPHORUS SPECTROSCOPY
ā¢ NMR has been used to study 31P-containing molecules such as
oligonucleotides, nucleotides, proteins, and phosphosugars.
ā¢ At 1.5 T a typical spectrum shows peaks from phosphomonoeasters
(PME), inorganic phosphates (Pi), phosphodiesters (PDE),
phosphocreatine(PCr) and the a,b and g phosphorus atoms of ATP.
ā¢ Role in Liver : The ratio PME/PDE has been viewed as an indirect
measure of disease severity within the liver, and the level of Pi has
been reported to reflect hepatic inflammation.
ā¢ Hepatic adenosine triphosphate levels most probably reflect the
hepatic mass and hepatic bioenergetics and have been observed to
be significantly reduced in cirrhotic livers.
ā¢ it is been studied as a technique for the noninvasive assessment of
host-related complications in pediatric patients after liver
transplantation.
47. In vivo hepatic phosphorus-
31 MR spectra of healthy 7-
year-old girl as control
subject (spectrum A),
8-year-old girl with good
graft function after liver
transplantation (spectrum
B),
and 11-year-old girl with
chronic hepatitis after liver
transplantation (spectrum
C). Spectra A and B show
similar spectral profile, but
there is marked elevation in
phosphomonoester (PME)
resonance (arrow) in
spectrum
Ref : A Noninvasive Assessment of Graft Status with Correlation with Liver
FunctionTests and Liver Biopsy by Winnie C. W. Chu1 et al ; AJNR 184/May 2005
48. 31- PHOSPHORUS SPECTROSCOPY
ā¢ Beadle and Frenneaux (2010) noted that 31-phosphorous ((31)P) MRS is a
technique that allows the non-invasive characterization of the biochemical
and metabolic state of the myocardium in vivo.
ā¢ Magnetic resonance spectroscopy can assess cardiac metabolism without
the need for external radioactive tracers.
ā¢ (31)P MRS provides information on the underlying metabolic abnormalities
that are fundamental to common conditions including ischemic heart disease,
cardiomyopathy, hypertrophy and valvular disease.
ā¢ (31)P MRS could potentially also have a role to play in assessing response
to therapy as well as the effectiveness of metabolic modulating agents.
ā¢ However, the use of MRS is currently limited to research due to its poor
reproducibility, low spatial and temporal resolution, and long acquisition
times. With technical advances in both the spectrometers and post-
processing, MRS is likely to play a role in the future of multi-modal non-
invasive cardiac assessment.
49. SODIUM SPECTROSCOPY
ā¢ For Measuring Cartilage GAG
ā¢ The extracellular molecules of cartilage contain carboxyl, sulfate, and
amino groups that are ionized under physiological conditions.
ā¢ Because collagen has nearly equal numbers of anionic and cationic
groups, it contributes little net charge.
ā¢ In contrast, the glycasaminoglycan (GAG) side chains of the
proteoglycan contain up to two anionic groups per disaccharide
subunit and thus provide a net negative charge to the matrix.
ā¢ Since these ionic groups are "fixed" to the solid matrix they are
referred to as "fixed charge", and the density of charge is referred to
as the fixed charge density, or FCD.
50. ā¢ The relationship between FCD and sodium ion concentration
hold on a spatially localized basis, and thus an image of sodium
concentration can be related to an image of FCD, or GAG
concentration
51. CONCLUSION
ā¢ MR spectroscopy provides a measure of brain chemistry.
ā¢ The most common nuclei that are used are 1H (proton), 23Na
(sodium), 31P (phosphorus).
ā¢ Proton spectroscopy is easier to perform and provides much higher
signal-to-noise than either sodium or phosphorus.
ā¢ Proton MRS can be performed within 10-15 minutes and can be
added on to conventional MR imaging protocols.
ā¢ It can be used to serially monitor biochemical changes in tumors,
stroke, epilepsy, metabolic disorders, infections, and
neurodegenerative diseases.
ā¢ The MR spectra do not come labelled with diagnoses.
ā¢ They require interpretation and should always be correlated with the
MR images before making a final diagnosis.