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Shabnam Mousavi. MRI Technologist
Magnetic Resonance Spectroscopy
Presented By:
Seyedeh Shabnam Mousavi Gezafroodi
Medical Physics M.Sc.
MRS
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 Introduction
 Physics
 Techniques
 Indication
 Case studies
 Conclusion
 References
Outline
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Shabnam Mousavi. MRI Technologist
Introduction
MRS is a non-invasive, ionizing-radiation-free analytical and physiological
technique 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
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Shabnam Mousavi. MRI Technologist
Introduction
 MR spectroscopy is the use of magnetic resonance in quantification of
metabolites and the study of their distribution in different tissues
 Rather than displaying MRI proton signals on a gray scale as an image,
depending on its relative signal strength, MRS displays the quantities as a
spectrum
 The resonance frequency of each metabolites is represented on a graph and
expressed as parts per million(ppm).
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Physics
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 Theoretically MRS can be performed with spins or nuclei of 1H, 13C, 19F,
23Na and 31P
 But In present, MRS clinical uses are mainly 1H & 31P spectroscopy
 The aim of MRS itself is to detect small metabolites. To detect these small
metabolites large signal from some protons need to be suppressed.
Different protons?
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Shabnam Mousavi. MRI Technologist
 For MR imaging, the total signal from all the protons in each voxel is used to
make the image
 If all the signal were used for MRS, the fat and water peaks would be huge
and scaling would make the other metabolite peaks invisible.
 Fat and water are eliminated
 Fat is avoided by placing the voxel for MRS within the brain, away from the
fat in bone marrow and scalp
 and what about water? …
Are all signals useful?
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 Spectral content of brain MR signal
Proton MRS signal
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Shabnam Mousavi. MRI Technologist
 It forms the basis of MRS Protons precess at different frequencies in
different chemical environment .This phenomenon is called chemical shift
 So different metabolites give peak at different position because of chemical
shift
 Shielding factors influence the position of the peak
 It is expressed as PPM(parts per million)
 1 PPM=1millionth of Larmor frequency.
Chemical shift and shielding
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Shabnam Mousavi. MRI Technologist
The Chemical shift is measure of how far the signal is from the reference signal
The reference point of an NMR spectrum is defined by position of TMS (0 ppm)
Chemical shift
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Shabnam Mousavi. MRI Technologist
 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
PRINCIPLES
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Shabnam Mousavi. MRI Technologist
Chemical elements having different atomic numbers such as hydrogen ('H) and
phosphorus (31P) resonate at different Larmor RFs
MR spectroscopy provides a measure of brain chemistry. The most common nuclei
that are used are 1H (proton), 23Na (sodium), 31P (phosphorus)
Proton spectroscopy is easier to perform and provides much higher signal-to-noise
than either sodium or phosphorus.
MRS can be performed within 10-15 minutes and can be added on to conventional
MR imaging protocols
It can be used to serially monitor biochemical changes in metabolic disorders and
diseases after interpretation
PRINCIPLES
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Technique
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Shabnam Mousavi. MRI Technologist
 MR spectroscopy is conducted on the same machine as conventional MRI
 Spectroscopy is a series of tests that are added to the MRI scan to measure the
chemical metabolism of a suspected lesion
 There are several different metabolites, or products of metabolism, that can be
measured to differentiate between diseases
How does MRS work?
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 Single voxel
proton MRS provides a rapid biochemical profile of a localized volume within a
region of interest
 Multi voxel
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
Methods
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 SINGLE-VOXEL MR SPECTROSCOPY
• Less advance
• Volume averaging
• Small area of coverage
• Short TE technique
• Acquires spectra from single small
voxel
• Short acquisition times
• Histologically simpler lesions
Two forms
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 MULTI-VOXEL MR SPECTROSCOPY
• More technically advanced technique
• Small voxel size: dec. volume averaging
• Large volume of coverage
• Long TE technique
• Acquires spectra from numerous small
voxels
• Long acquisition times
• For complex lesions
Shabnam Mousavi. MRI Technologist
Single & Multi voxel proton MRS
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1) Shimming the magnetic field
2) Suppressing the water signal
3) Choosing Spectroscopic Technique
MRS acquisition TECHNIQUES
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• The process of making magnetic field homogenous is called shimming
• By tuning different pulses in the x, y, and z directions
• The homogenecity required for MRI is about .5 ppm whereas for MRS it is
about .1 ppm
1) Shimming
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• Because water molecules contain hydrogen, and the relative concentration
of water to metabolite is about 10,000:1, the water signal must be
suppressed or the metabolite peaks will not be discernible in the spectra
• This is achieved by adding water suppression pulses
2) Suppressing the water signal
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Four methods commonly used for localization in clinical practice:
STEAM (Stimulated echo acquisition method)
• three 90 degree excited pulse applied along three planes. Short TE (20ms), Single voxel
PRESS (point resolved spectroscopy)
• one 90 degree and two 180 degree pulse are applied along three planes. longer TE (270ms)
• Twice the SNR of STEAM , Short and long TE - single voxel possible
ISIS(Image Selective In vivo Spectroscopy)
Used in 31P spectroscopy
CSI(chemical shift Imaging)
Used for multi voxel spectrosopy
3) Spectroscopic technique
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1) Single volume:
(STEAM) & (PRESS)
It gives a better signal-to noise ratio
2) Multivolume MRS:
(CSI) & (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.
MRS TECHNIQUES
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• Voxel placement in single-voxel MR spectroscopy studies of tumors is critical to the
accurate characterization of lesion histopathology
• Specifically, inclusion of the edge of an enhancing lesion in the MR spectroscopy voxel
improves accuracy
• Voxel placement in the center of a lesion with frank cavitation increases the likelihood
that cellular breakdown products will dominate the spectral pattern
 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.
Placement
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MRS acquisition technique
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• Improved SNR is obtained at longer TR
• TEs commonly used are 20-30ms,135-145ms & 270ms. At longer TEs more than
135ms peaks of major brain metabolites are visible
 TR: 1500 ms
 TE: 35 ms
 Voxel Size: 2 x 2 x 2 cm
 Voxel Location: dependent on lesion
 Cingulate gyrus - GM
 Parietal - WM
Acquisition Parameters
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 Short echo times are indicated for the study of metabolic and diffuse diseases
 By using long echo times (more than 135 ms), 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
 EFFECT OF TE ON THE PEAKS:
Echo time
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 SHORT TE (35 ms)
• mI
• LACTATE
• LIPIDS
• GLUTAMATE /GLUTAMINE
 BOTH SHORT 35 AND LONG TE (144 ms)
• NAA
• CREATINE
• CHOLINE
• LACTATE signal lowered
METABOLITES in different TE
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.
Different TEs
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 Lactate
• peak is doublet
• Inversion below the baseline at 144 ms
• Persists at TE 270 ms.
 Lipid
• peak is broad
• Has a shoulder to left
• Suppressed at TE 270 ms
Lactate Vs Lipid
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Lactate
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TE=35ms TE=144ms TE=270ms
Shabnam Mousavi. MRI Technologist
• 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
Interpretation of the spectroscopic curve
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• 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
Normal spectral data obtained at intermediate echo-time
by single voxel
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• Appropriate shimming
• Adequate water suppression by CHESS
• Adequate voxel adjustment to avoid blood, bone, CSF ,cysts and air since
susceptibility artifacts may hamper the expected normal molecular distributions.
How to obtain quality spectra?
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Normal MRS
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The brain Metabolites that
are commonly seen on
MR spectrum
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 Each metabolite appears at a specific ppm, and each one reflects specific
cellular and biochemical processes
 NAA: is a neuronal marker and decreases with any disease that adversely
affects neuronal integrity
 Creatine: provides a measure of energy stores.
 Choline: is a measure of increased cellular turnover and is elevated in tumors
and inflammatory processes
 The common way to analyze clinical spectra is to look at metabolite ratios,
namely NAA/Cr, NAA/Cho, and Cho/Cr
What can be derived from the spectrum?
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• METABOLITE RATIOS:
Shabnam Mousavi. MRI Technologist
1.No. of signal:
It represents how many types of protons are present in the molecule.
2.Positions of signals:
Represent electronic environment of protons
3.Intensity of signal:
Represents how many protons of each type are present
4.Splitting of signals:
Represents no. of neighboring non equivalent protons (Follows n +1 rule)
Interpretation of signal
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 Detection of frequency dependent signals from individual metabolites
 Interpretation is based on identity of chemical and concentration
 Baseline normal spectra – constant
 Concentration of each metabolites alter in a reproducible pattern - Abnormal
spectra = DISEASE PATTERN
Interpretation of graph
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 Height
 width
 size & Frequency of each peak
 Combining horizontal and vertical information
 Presence / absence of peak
 Ratio of metabolites
Spectrum variables
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 Hunter’s angle
• A quick, useful method to read MRS
• If the angle and peaks roughly corresponded to the 450:
probably normal
Spectrum angle
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NAA Regional Variations
• NAA peak: Highest due to N acetyl group
• Marker of neuronal / axonal viability and density
• Evenly distributed in Cerebral hemisphere
• Less in hippocampus and cerebellum
• Decreases with loss of neuronal integrity.
Main metabolites
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Shabnam Mousavi. MRI Technologist
Creatine
• Energy stores
• Cr 1 - 3.0 ppm
• Cr 2 - 3.9 ppm
• Marker of intact brain Energy Metabolism
• Reference for interpretation of ratio
• Higher in grey matter than white matter
• Higher in thalamus and cerebellum
Main metabolites
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Shabnam Mousavi. MRI Technologist
Choline
• Cho - 3.2 ppm
• Present in Cell membrane
• Choline released during disease from pool
• Choline - Increased with increased cellular turnover
• Elevated in tumors and inflammation
Choline Regional Variations
• Slightly higher in white matter than gray
• Higher in thalamus and cerebellum
• More choline in pons and terminal zones of myelination
Main metabolites
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Myo-Inositol
• Cell Volume Regulator - Osmolyte
• mI - 3.5 ppm ; 4.0 ppm.
• Present in astrocytes
• Astrocyte /glial marker - Product of myelin degradation
• Important marker in grading gliomas
Main metabolites
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• Lactate
• Doublet at 1.3 ppm
• Accelerated glycolysis /Anaerobic glycolysis
• Peak is inverted at TE -144ms which helps to distinguish lactate from lipids
• Not seen in normal condition
Main metabolites
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Lipids
• Lip 1 - 0.9 ppm; Lip 2 - 1.3 - 1.4 ppm
• Broad based
• Sign of brain injury
• Normally Bound - Not seen
• Seen when there is cell death and cell membrane destruction
• Indicates necrosis and / or disruption of myelin
• Difficult to differentiate from macromolecules
• Non significant lipid – from scalp contamination
Main metabolites
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Glutamate & Glutamine (Glx)
• Neurotransmitters
• Beta, Gamma Glx - 2.0 - 2.5 ppm
• Alfa Glx - 3.6 - 3.8 ppm
Glutamine is astrocyte marker
• Glutamate – Neurotransmiter - neurotoxin in excess amount.
• Main ammonia intake route
Main metabolites
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Main metabolites
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• Neonates
Cho. and mi is high
Gradual increase in NAA due to neuronal maturation
After 2 yrs spectrum is identical to adult
• Elderly
Elevated Cho.
Elevated Cr.
Diminished NAA
Age variation
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• Obtain whole-head multi-planar scout images
• These will be used to set the boundaries of the spectroscopy volume and for placement of saturation bands
• Pick type of MRS coverage
• The first decision is to choose between Single Voxel Spectroscopy (SVS) and Multi-Voxel Chemical Shift Imaging (CSI). If MVSI is
chosen then either a 2D method (imaging an array of voxels in a single plane) or 3D method (imaging an entire volume of voxels)
must then be selected. In general, SVS methods are easier and quicker to perform with higher signal-to-noise than MVSI, but suffer
from poorer spatial resolution
• Select MRS technique and parameters
• Although several MRS sequences are available, some variant of PRESS (Point REsolved SpectoScopy). is most commonly used.
Other options include STEAM (Stimulated Echo Acquisition Mode) or simple spin-echo acquisition. Imaging parameters such as TR,
TE, FOV, NEX, and voxel size(s) must also be specified. Typically a medium length TR is chosen (1500-2000 msec). Separately
acquired short TE (~30 msec) and medium TE (~144 msec) studies are both usually performed to reveal various metabolites to best
advantage.
How do you perform a "standard" MRS exam of
the brain?
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• Place MRS volume over anatomy of interest
• Care must be taken that the imaging region does not include fat-containing scalp or bone marrow that may contaminate the
spectrum. Outer volume saturation bands are generally required to be placed over these areas to suppress signal from fat
• Shimming and Calibration
• Shimming is fine-tuning of the magnetic field homogeneity by adjusting currents passing though specialized shim coils next to
the gradients. Automated shimming is usually sufficient for routine head MRS studies, but manual adjustments may be
necessary.
• Perform MRS
• Typical image acquisition times are 5-15 minutes, depending on technique and size of volume studied.
• View/analyze spectra
• Separate spectra are generated for each MRS voxel which can then be analyzed visually or overlaid as color maps on anatomic
images. Optional post-processing may be performed to identify and quantify detected peaks.
How do you perform a "standard" MRS exam of
the brain? (cont.)
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MRS uses
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Brain tumors
• MRS can be used to determine the degree of malignancy
• As malignancy increases, NAA and Cr decrease, and chol, lact, and lipids increase
• NAA decreases as tumor growth displaces or destroys neurons
• Very malignant tumors have high metabolic activity and deplete the energy stores,
resulting in reduced Cr
• Very hyper cellular tumors with rapid growth elevate the Chol levels
• Lipids are found in necrotic portions of tumors
• Lac appears when tumors outgrow their blood supply and start utilizing anaerobic
glycolysis
 Key feature of gliomas is elevated choline beyond the margin of enhancement due to
infiltration of tumor into the adjacent brain tissue.
 Elevated alanine is a signature of meningiomas
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Grade
• Cho/NAA ratio - Most sensitive index for tumor cell density and proliferation
• Marker of tumor infiltration
• High Cho/NAA and Cho/Cr – Fast growing and high grade neoplasm
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Tumor recurrence vs. Radiation necrosis
• A common clinical problem is distinguishing tumor recurrence from
radiation effects several months following surgery and radiation therapy
• Elevated choline is a marker for recurrent tumor. Radiation change generally
exhibits low NAA, creatine, and choline on spectroscopy
• If radiation necrosis is present, the spectrum may reveal elevated lipids and
lactate.
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GBM/Mets/Abscess
 Multi voxel PRESS sequence with intermediate TE -for elevation of Cho in
enhancing rim and in peri-lesional T2 hyperintensity
• If Cho is elevated in both areas - GBM
• Elevated in rim - Mets
• Detection of peptides and amino acids in rim - Pyogenic abscess
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Cerebral ischemia and infarction
• When the brain becomes ischemic, it switches to anaerobic glycolysis and
lactate accumulates
• Markedly elevated lactate is the key spectroscopic feature of cerebral
hypoxia and ischemia
• If cerebral infarction ensues, lipids increase.
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Trauma
• MR spectroscopy is not routinely used in the acute setting of head injuries
• when the patient has stabilized, MRS is helpful to assess the degree of
neuronal injury and predict patient outcomes
• 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
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Infectious disease
• Brain abscesses destroy or displace brain tissue, so NAA is not present
• The voxel should include the abscess cavity to detect the breakdown
products of these lesions
• Lactate, cytosolic acid, alanine, and acetate are characteristic metabolites in
bacterial abscesses
• Toxoplasmosis and tuberculomas show prominent peaks from lactate and
lipids
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Key points
 High Cho - High tumor cell density & high vascular proliferation
 Low Cho and elevation of lipids – Necrosis
 Cho higher enhancing rim -may be the faster growing side of the tumor
 Normal Cho and slightly decreased NAA- Vasogenic edema
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CASE REPORTS
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 A 50 y M with fever, headache and Lt hemiparesis
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
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 A 67 YR M WITH POSTERIOR FOSSA SOL
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
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 Serial MR spectroscopic data from a 25-year-old lady who was under 6 monthly
imaging follow-up for a low-grade glioma
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 A 48 Y F WITH HEADACHE AND LEFT HEMIPARESIS
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
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 A 27 Y M WITH MULTIPLE NODULAR LESIONS IN BRAIN
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
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 A 14 Y M WITH REFRACTORY CPS PLANNED FOR
SURGERY
•MRS of Left anterior hippocampus showed
smaller NAA peak (33% less) compared to Right
indicating a left temporal seizure focus
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 A 48YR F WITH PROVEN GLIOBLASTOMA MULTIFORME
TREATED WITH SURGERY, EXTERNAL BEAM RADIATION
AND INTERSTITIAL BRACHYTHERAPY.
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)
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 76 Y M PRESENTED WITH RECENT MEMORY LOSS
Proton MRS in hippocampal region shows MI peak,
decreased NAA and elevated MI/Cr ratio
•Dx - Alzheimer’s Disease
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 Patient with known diagnosis of MELAS with new onset of visual symptoms.
(Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)
MR spectroscopy (TE=144 ms) from the right occipital abnormality shows an
inverted doublet at 1.3 ppm (arrows) consistent with a lactate peak.
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 7 MONTH INFANT WITH DELAYED MILESTONES & SPASTICITY
MRS show markedly raised NAA peak as compared to
control subject
Dx – Canavan’s disease
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• 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.
Canavan disease
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 5 Y CHILD WITH SEIZURES
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
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• Ischemic stroke- appearance of lactate peak within minutes of ischemia. In
chronic phase NAA is suppressed
• Multiple sclerosis- Increased Cho due to active demylination. Lipid and Lac may
also rise. Presence of MI suggests severe demylination
• Hepatic encephalopathy-: increased glutamate, decreased myoinositol
• Phenylketonuria- increased Phenylalanine peak at 7.3ppm
• AIDS dementia- increased MI and Gln detected. MRS may help in detection of
subclinical disease, opportunistic infections and monitoring ART
MRS IN OTHER CONDITIONS
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• 135 TE
• Inv Of AA,0.9 ppm, Lac, 1.33 ppm, and Ala, 1.47 ppm peaks
• Pyogenic abscess
Case report
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• STEAM
• TE 35, only Lip and Lac at 1.3 ppm.
• TE 135 spectrum, phase reversal & reduction in signal
• Tuberculous abscesses
Case report
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• TE 135 proton MR spectrum from core of lesion – inverted AA and Lac
peaks
• Multiple signal (*) at 3.6–3.8 ppm
• Fungal abscess
Case report
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• MRS with TE 35 - Lac at 1.33 ppm, acetate at 1.92 ppm, and succinate at 2.4 ppm
• At TE 135 - Lac and Ala at 1.5 ppm show phase reversal while Ace and Suc show
normal phase
• Hydatid cyst:
Case report
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Multiple sclerosis
• Long TE spectra in acute and chronic MS lesions.
– Both - Elevated Cho and reduced NAA
– Only acute lesion - Elevated lactate
• Short TE spectra from acute lesion and normal brain for comparison
– Increased mI, choline, and lipids, slightly decreased Cr and NAA.
Case report
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ee
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Whole brain MRS analysis Metabolic parametric maps
RECENT ADVANCES
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• Breast spectroscopy
GluCEST(Chemical exchange saturaton transfer MRS)
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RECENT ADVANCES
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Prostate MRS Liver MRS to see Fat fraction
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RECENT ADVANCES
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FUNCTIONAL MRS
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 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 fMRS and PET
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CLINICAL APPLICATIONS OF MRS:
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Conclusion
 Proton MRS of the brain is useful whenever biochemical or metabolic assessment may
be necessary, such as in differential diagnosis of focal brain lesions
 Diagnosis , grading of tumors and response to treatment and follow-up radiation
therapy for patients with brain neoplasms
 Direct the surgeon to the most metabolically active part of the tumor for biopsy to
obtain accurate grading of the malignancy
 Diagnosis and prognosis of brain ischemic and traumatic lesions
 Assessment of epilepsy and demyelinating diseases
 Biochemical alterations in hepatic encephalopathies and neuropediatric affections
such as brain tumors, inborn errors of metabolism and hypoxic encephalopathy 105
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Conclusion
 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
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Conclusion
 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
 They require interpretation and should always be correlated with the MR
images before making a final diagnosis
107
Shabnam Mousavi. MRI Technologist
108
 Handbook of instrumental techniques for analytical chemistry, Settle F, ch 17.
 MR spectroscopy in metabolic disorders of the brain, Yilmaz U, Radiologe 2017 Jun;57(6):438-442.
 Magnetic resonance spectroscopy: basics. Bluml S. 2013 XIV (402-416)
 Proton Mr Spectroscopy, Fundamental Physics and Clinical Applications, Kemal Arda et al, Austin
oncology 2016
 MR spectroscopy and spectroscopic imaging of the brain. Zhu H, Barker PB. Methods Mol Biol.
2011;711:203–226.
 Proton Magnetic Resonance Spectroscopy: Technique for the Neuroradiologist. Kim M Cecil,
Neuroimaging clin N Am.2013; 23(3): 381-392.
 In vivo magnetic resonance spectroscopy: basic methodology and clinical applications. Marinette
van der graff. Eur biophys J. 2010 Mar; 39(4): 527–540.
References
Shabnam Mousavi. MRI Technologist
109
Shabnam Mousavi. MRI Technologist
110
Shabnam Mousavi. MRI Technologist
ee
MRS TECHNIQUES
111
Shabnam Mousavi. MRI Technologist
• N-Acetyl aspertate 2.02
• N-Acetyl aspertate glutamate 2.05
• Choline containing compound 3.22
• Creatine containing compound 3.02
• Myo-inositol 3.56
• Glucose 3.55
• Glutamate/ glutamine 2-2.5, 3.4-3.7
• Lipid 1.3
• Lactate 1.3
• Alanine 1.48
Major spectral peaks assigned in human brain proton
spectra from white matter
112
Shabnam Mousavi. MRI Technologist
113
 A patient with right HS
• Short TE (35msec) spectra at 3T obtained in the
left and right hippocampal formation 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
Shabnam Mousavi. MRI Technologist
Single Volume MRS
MRS TECHNIQUES
114
Shabnam Mousavi. MRI Technologist
115
Inborn errors of metabolism
• Canavan and Salla disease show an elevated NAA
• Maple syrup urine disease -Branched-chain amino acids at 0.9 ppm.
• Phenylketonuria -Small phenylalanine signal at 7.36ppm (i.e. downfield of
water)
• Non-ketotic hyperglycinemia -Glycine at 3.55 ppm (use long TE to distinguish
from mI)
Case report
Shabnam Mousavi. MRI Technologist
116
Canavan’s disease- AR
• Deficiency of aspartoacylase an enzyme that deacetylates NAA, Increased
free acetate
• Hypotonia and macrocephaly
• Symmetrical confluent subcortical WM T2 prolongation & Centripetal spread
• Bilateral involvement of globi pallidi, thalami, cerebellum and brainstem
Case report
Shabnam Mousavi. MRI Technologist
117
OTHER CONDITIONS:
Hepatic encephalopathy: increased glutamate, decreased myoinositol
Phenylketonuria: increased Phenylalanine peak at 7.3ppm
Parkinson’s disease
Motor neuron disease
Psychiatric disease
Shabnam Mousavi. MRI Technologist
118
• Neuronal dysfunction & cell death
• Metabolite changes in idiopathic Parkinson’s disease are inconsistent
• Multiple system atrophy -reduction in NAA and NAA/Cr ratio when compared
with IPD
• Lactate increased in Huntington’s disease.
Neurodegenerative diseases
Shabnam Mousavi. MRI Technologist
119
 Proton MRS of the brain is useful whenever biochemical or metabolic assessment may
be necessary, such as in differential diagnosis of focal brain lesions
 Diagnosis , grading of tumors and response to treatment and follow-up radiation
therapy for patients with brain neoplasms
 Direct the surgeon to the most metabolically active part of the tumor for biopsy to
obtain accurate grading of the malignancy
 Diagnosis and prognosis of brain ischemic and traumatic lesions
 Assessment of epilepsy and demyelinating diseases
 Biochemical alterations in hepatic encephalopathies and neuropediatric affections
such as brain tumors, inborn errors of metabolism and hypoxic encephalopathy
Shabnam Mousavi. MRI Technologist

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MRS. Shabnam Mousavi.pptx- Magnetic Resonance Spectroscopy

  • 1. 1 Shabnam Mousavi. MRI Technologist
  • 2. Magnetic Resonance Spectroscopy Presented By: Seyedeh Shabnam Mousavi Gezafroodi Medical Physics M.Sc. MRS 2 Shabnam Mousavi. MRI Technologist
  • 3.  Introduction  Physics  Techniques  Indication  Case studies  Conclusion  References Outline 3 Shabnam Mousavi. MRI Technologist
  • 4. Introduction MRS is a non-invasive, ionizing-radiation-free analytical and physiological technique 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 Shabnam Mousavi. MRI Technologist
  • 5. Introduction  MR spectroscopy is the use of magnetic resonance in quantification of metabolites and the study of their distribution in different tissues  Rather than displaying MRI proton signals on a gray scale as an image, depending on its relative signal strength, MRS displays the quantities as a spectrum  The resonance frequency of each metabolites is represented on a graph and expressed as parts per million(ppm). 5 Shabnam Mousavi. MRI Technologist
  • 6. 6 Shabnam Mousavi. MRI Technologist
  • 7. 7 Shabnam Mousavi. MRI Technologist
  • 9.  Theoretically MRS can be performed with spins or nuclei of 1H, 13C, 19F, 23Na and 31P  But In present, MRS clinical uses are mainly 1H & 31P spectroscopy  The aim of MRS itself is to detect small metabolites. To detect these small metabolites large signal from some protons need to be suppressed. Different protons? 9 Shabnam Mousavi. MRI Technologist
  • 10.  For MR imaging, the total signal from all the protons in each voxel is used to make the image  If all the signal were used for MRS, the fat and water peaks would be huge and scaling would make the other metabolite peaks invisible.  Fat and water are eliminated  Fat is avoided by placing the voxel for MRS within the brain, away from the fat in bone marrow and scalp  and what about water? … Are all signals useful? 10 Shabnam Mousavi. MRI Technologist
  • 11.  Spectral content of brain MR signal Proton MRS signal 11 Shabnam Mousavi. MRI Technologist
  • 12.  It forms the basis of MRS Protons precess at different frequencies in different chemical environment .This phenomenon is called chemical shift  So different metabolites give peak at different position because of chemical shift  Shielding factors influence the position of the peak  It is expressed as PPM(parts per million)  1 PPM=1millionth of Larmor frequency. Chemical shift and shielding 12 Shabnam Mousavi. MRI Technologist
  • 13. The Chemical shift is measure of how far the signal is from the reference signal The reference point of an NMR spectrum is defined by position of TMS (0 ppm) Chemical shift 14 Shabnam Mousavi. MRI Technologist
  • 14.  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 PRINCIPLES 15 Shabnam Mousavi. MRI Technologist
  • 15. Chemical elements having different atomic numbers such as hydrogen ('H) and phosphorus (31P) resonate at different Larmor RFs MR spectroscopy provides a measure of brain chemistry. The most common nuclei that are used are 1H (proton), 23Na (sodium), 31P (phosphorus) Proton spectroscopy is easier to perform and provides much higher signal-to-noise than either sodium or phosphorus. MRS can be performed within 10-15 minutes and can be added on to conventional MR imaging protocols It can be used to serially monitor biochemical changes in metabolic disorders and diseases after interpretation PRINCIPLES 16 Shabnam Mousavi. MRI Technologist
  • 17.  MR spectroscopy is conducted on the same machine as conventional MRI  Spectroscopy is a series of tests that are added to the MRI scan to measure the chemical metabolism of a suspected lesion  There are several different metabolites, or products of metabolism, that can be measured to differentiate between diseases How does MRS work? 19 Shabnam Mousavi. MRI Technologist
  • 18.  Single voxel proton MRS provides a rapid biochemical profile of a localized volume within a region of interest  Multi voxel 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 Methods 20 Shabnam Mousavi. MRI Technologist
  • 19.  SINGLE-VOXEL MR SPECTROSCOPY • Less advance • Volume averaging • Small area of coverage • Short TE technique • Acquires spectra from single small voxel • Short acquisition times • Histologically simpler lesions Two forms 21  MULTI-VOXEL MR SPECTROSCOPY • More technically advanced technique • Small voxel size: dec. volume averaging • Large volume of coverage • Long TE technique • Acquires spectra from numerous small voxels • Long acquisition times • For complex lesions Shabnam Mousavi. MRI Technologist
  • 20. Single & Multi voxel proton MRS 22 Shabnam Mousavi. MRI Technologist
  • 21. 1) Shimming the magnetic field 2) Suppressing the water signal 3) Choosing Spectroscopic Technique MRS acquisition TECHNIQUES 23 Shabnam Mousavi. MRI Technologist
  • 22. • The process of making magnetic field homogenous is called shimming • By tuning different pulses in the x, y, and z directions • The homogenecity required for MRI is about .5 ppm whereas for MRS it is about .1 ppm 1) Shimming 24 Shabnam Mousavi. MRI Technologist
  • 23. • Because water molecules contain hydrogen, and the relative concentration of water to metabolite is about 10,000:1, the water signal must be suppressed or the metabolite peaks will not be discernible in the spectra • This is achieved by adding water suppression pulses 2) Suppressing the water signal 25 Shabnam Mousavi. MRI Technologist
  • 24. Four methods commonly used for localization in clinical practice: STEAM (Stimulated echo acquisition method) • three 90 degree excited pulse applied along three planes. Short TE (20ms), Single voxel PRESS (point resolved spectroscopy) • one 90 degree and two 180 degree pulse are applied along three planes. longer TE (270ms) • Twice the SNR of STEAM , Short and long TE - single voxel possible ISIS(Image Selective In vivo Spectroscopy) Used in 31P spectroscopy CSI(chemical shift Imaging) Used for multi voxel spectrosopy 3) Spectroscopic technique 26 Shabnam Mousavi. MRI Technologist
  • 25. 1) Single volume: (STEAM) & (PRESS) It gives a better signal-to noise ratio 2) Multivolume MRS: (CSI) & (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. MRS TECHNIQUES 27 Shabnam Mousavi. MRI Technologist
  • 26. • Voxel placement in single-voxel MR spectroscopy studies of tumors is critical to the accurate characterization of lesion histopathology • Specifically, inclusion of the edge of an enhancing lesion in the MR spectroscopy voxel improves accuracy • Voxel placement in the center of a lesion with frank cavitation increases the likelihood that cellular breakdown products will dominate the spectral pattern  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. Placement 28 Shabnam Mousavi. MRI Technologist
  • 27. MRS acquisition technique 29 Shabnam Mousavi. MRI Technologist
  • 28. • Improved SNR is obtained at longer TR • TEs commonly used are 20-30ms,135-145ms & 270ms. At longer TEs more than 135ms peaks of major brain metabolites are visible  TR: 1500 ms  TE: 35 ms  Voxel Size: 2 x 2 x 2 cm  Voxel Location: dependent on lesion  Cingulate gyrus - GM  Parietal - WM Acquisition Parameters 30 Shabnam Mousavi. MRI Technologist
  • 29.  Short echo times are indicated for the study of metabolic and diffuse diseases  By using long echo times (more than 135 ms), 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  EFFECT OF TE ON THE PEAKS: Echo time 32 Shabnam Mousavi. MRI Technologist
  • 30.  SHORT TE (35 ms) • mI • LACTATE • LIPIDS • GLUTAMATE /GLUTAMINE  BOTH SHORT 35 AND LONG TE (144 ms) • NAA • CREATINE • CHOLINE • LACTATE signal lowered METABOLITES in different TE 33 Shabnam Mousavi. MRI Technologist
  • 32.  Lactate • peak is doublet • Inversion below the baseline at 144 ms • Persists at TE 270 ms.  Lipid • peak is broad • Has a shoulder to left • Suppressed at TE 270 ms Lactate Vs Lipid 35 Shabnam Mousavi. MRI Technologist
  • 33. Lactate 36 TE=35ms TE=144ms TE=270ms Shabnam Mousavi. MRI Technologist
  • 34. • 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 Interpretation of the spectroscopic curve 37 Shabnam Mousavi. MRI Technologist
  • 35. • 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 Normal spectral data obtained at intermediate echo-time by single voxel 38 Shabnam Mousavi. MRI Technologist
  • 36. • Appropriate shimming • Adequate water suppression by CHESS • Adequate voxel adjustment to avoid blood, bone, CSF ,cysts and air since susceptibility artifacts may hamper the expected normal molecular distributions. How to obtain quality spectra? 39 Shabnam Mousavi. MRI Technologist
  • 37. Normal MRS 40 Shabnam Mousavi. MRI Technologist
  • 38. The brain Metabolites that are commonly seen on MR spectrum 41 Shabnam Mousavi. MRI Technologist
  • 39. 42 Shabnam Mousavi. MRI Technologist
  • 40. 43 Shabnam Mousavi. MRI Technologist
  • 41. 44 Shabnam Mousavi. MRI Technologist
  • 42. 46 Shabnam Mousavi. MRI Technologist
  • 43.  Each metabolite appears at a specific ppm, and each one reflects specific cellular and biochemical processes  NAA: is a neuronal marker and decreases with any disease that adversely affects neuronal integrity  Creatine: provides a measure of energy stores.  Choline: is a measure of increased cellular turnover and is elevated in tumors and inflammatory processes  The common way to analyze clinical spectra is to look at metabolite ratios, namely NAA/Cr, NAA/Cho, and Cho/Cr What can be derived from the spectrum? 47 Shabnam Mousavi. MRI Technologist
  • 44. 48 • METABOLITE RATIOS: Shabnam Mousavi. MRI Technologist
  • 45. 1.No. of signal: It represents how many types of protons are present in the molecule. 2.Positions of signals: Represent electronic environment of protons 3.Intensity of signal: Represents how many protons of each type are present 4.Splitting of signals: Represents no. of neighboring non equivalent protons (Follows n +1 rule) Interpretation of signal 49 Shabnam Mousavi. MRI Technologist
  • 46.  Detection of frequency dependent signals from individual metabolites  Interpretation is based on identity of chemical and concentration  Baseline normal spectra – constant  Concentration of each metabolites alter in a reproducible pattern - Abnormal spectra = DISEASE PATTERN Interpretation of graph 50 Shabnam Mousavi. MRI Technologist
  • 47.  Height  width  size & Frequency of each peak  Combining horizontal and vertical information  Presence / absence of peak  Ratio of metabolites Spectrum variables 51 Shabnam Mousavi. MRI Technologist
  • 48.  Hunter’s angle • A quick, useful method to read MRS • If the angle and peaks roughly corresponded to the 450: probably normal Spectrum angle 53 Shabnam Mousavi. MRI Technologist
  • 49. NAA Regional Variations • NAA peak: Highest due to N acetyl group • Marker of neuronal / axonal viability and density • Evenly distributed in Cerebral hemisphere • Less in hippocampus and cerebellum • Decreases with loss of neuronal integrity. Main metabolites 54 Shabnam Mousavi. MRI Technologist
  • 50. Creatine • Energy stores • Cr 1 - 3.0 ppm • Cr 2 - 3.9 ppm • Marker of intact brain Energy Metabolism • Reference for interpretation of ratio • Higher in grey matter than white matter • Higher in thalamus and cerebellum Main metabolites 55 Shabnam Mousavi. MRI Technologist
  • 51. Choline • Cho - 3.2 ppm • Present in Cell membrane • Choline released during disease from pool • Choline - Increased with increased cellular turnover • Elevated in tumors and inflammation Choline Regional Variations • Slightly higher in white matter than gray • Higher in thalamus and cerebellum • More choline in pons and terminal zones of myelination Main metabolites 56 Shabnam Mousavi. MRI Technologist
  • 52. Myo-Inositol • Cell Volume Regulator - Osmolyte • mI - 3.5 ppm ; 4.0 ppm. • Present in astrocytes • Astrocyte /glial marker - Product of myelin degradation • Important marker in grading gliomas Main metabolites 57 Shabnam Mousavi. MRI Technologist
  • 53. • Lactate • Doublet at 1.3 ppm • Accelerated glycolysis /Anaerobic glycolysis • Peak is inverted at TE -144ms which helps to distinguish lactate from lipids • Not seen in normal condition Main metabolites 58 Shabnam Mousavi. MRI Technologist
  • 54. Lipids • Lip 1 - 0.9 ppm; Lip 2 - 1.3 - 1.4 ppm • Broad based • Sign of brain injury • Normally Bound - Not seen • Seen when there is cell death and cell membrane destruction • Indicates necrosis and / or disruption of myelin • Difficult to differentiate from macromolecules • Non significant lipid – from scalp contamination Main metabolites 59 Shabnam Mousavi. MRI Technologist
  • 55. Glutamate & Glutamine (Glx) • Neurotransmitters • Beta, Gamma Glx - 2.0 - 2.5 ppm • Alfa Glx - 3.6 - 3.8 ppm Glutamine is astrocyte marker • Glutamate – Neurotransmiter - neurotoxin in excess amount. • Main ammonia intake route Main metabolites 60 Shabnam Mousavi. MRI Technologist
  • 57. 62 Shabnam Mousavi. MRI Technologist
  • 58. • Neonates Cho. and mi is high Gradual increase in NAA due to neuronal maturation After 2 yrs spectrum is identical to adult • Elderly Elevated Cho. Elevated Cr. Diminished NAA Age variation 63 Shabnam Mousavi. MRI Technologist
  • 59. • Obtain whole-head multi-planar scout images • These will be used to set the boundaries of the spectroscopy volume and for placement of saturation bands • Pick type of MRS coverage • The first decision is to choose between Single Voxel Spectroscopy (SVS) and Multi-Voxel Chemical Shift Imaging (CSI). If MVSI is chosen then either a 2D method (imaging an array of voxels in a single plane) or 3D method (imaging an entire volume of voxels) must then be selected. In general, SVS methods are easier and quicker to perform with higher signal-to-noise than MVSI, but suffer from poorer spatial resolution • Select MRS technique and parameters • Although several MRS sequences are available, some variant of PRESS (Point REsolved SpectoScopy). is most commonly used. Other options include STEAM (Stimulated Echo Acquisition Mode) or simple spin-echo acquisition. Imaging parameters such as TR, TE, FOV, NEX, and voxel size(s) must also be specified. Typically a medium length TR is chosen (1500-2000 msec). Separately acquired short TE (~30 msec) and medium TE (~144 msec) studies are both usually performed to reveal various metabolites to best advantage. How do you perform a "standard" MRS exam of the brain? 64 Shabnam Mousavi. MRI Technologist
  • 60. • Place MRS volume over anatomy of interest • Care must be taken that the imaging region does not include fat-containing scalp or bone marrow that may contaminate the spectrum. Outer volume saturation bands are generally required to be placed over these areas to suppress signal from fat • Shimming and Calibration • Shimming is fine-tuning of the magnetic field homogeneity by adjusting currents passing though specialized shim coils next to the gradients. Automated shimming is usually sufficient for routine head MRS studies, but manual adjustments may be necessary. • Perform MRS • Typical image acquisition times are 5-15 minutes, depending on technique and size of volume studied. • View/analyze spectra • Separate spectra are generated for each MRS voxel which can then be analyzed visually or overlaid as color maps on anatomic images. Optional post-processing may be performed to identify and quantify detected peaks. How do you perform a "standard" MRS exam of the brain? (cont.) 65 Shabnam Mousavi. MRI Technologist
  • 61. 66 Shabnam Mousavi. MRI Technologist
  • 62. MRS uses 67 Shabnam Mousavi. MRI Technologist
  • 63. Brain tumors • MRS can be used to determine the degree of malignancy • As malignancy increases, NAA and Cr decrease, and chol, lact, and lipids increase • NAA decreases as tumor growth displaces or destroys neurons • Very malignant tumors have high metabolic activity and deplete the energy stores, resulting in reduced Cr • Very hyper cellular tumors with rapid growth elevate the Chol levels • Lipids are found in necrotic portions of tumors • Lac appears when tumors outgrow their blood supply and start utilizing anaerobic glycolysis  Key feature of gliomas is elevated choline beyond the margin of enhancement due to infiltration of tumor into the adjacent brain tissue.  Elevated alanine is a signature of meningiomas 70 Shabnam Mousavi. MRI Technologist
  • 64. Grade • Cho/NAA ratio - Most sensitive index for tumor cell density and proliferation • Marker of tumor infiltration • High Cho/NAA and Cho/Cr – Fast growing and high grade neoplasm 71 Shabnam Mousavi. MRI Technologist
  • 65. Tumor recurrence vs. Radiation necrosis • A common clinical problem is distinguishing tumor recurrence from radiation effects several months following surgery and radiation therapy • Elevated choline is a marker for recurrent tumor. Radiation change generally exhibits low NAA, creatine, and choline on spectroscopy • If radiation necrosis is present, the spectrum may reveal elevated lipids and lactate. 72 Shabnam Mousavi. MRI Technologist
  • 66. GBM/Mets/Abscess  Multi voxel PRESS sequence with intermediate TE -for elevation of Cho in enhancing rim and in peri-lesional T2 hyperintensity • If Cho is elevated in both areas - GBM • Elevated in rim - Mets • Detection of peptides and amino acids in rim - Pyogenic abscess 73 Shabnam Mousavi. MRI Technologist
  • 67. Cerebral ischemia and infarction • When the brain becomes ischemic, it switches to anaerobic glycolysis and lactate accumulates • Markedly elevated lactate is the key spectroscopic feature of cerebral hypoxia and ischemia • If cerebral infarction ensues, lipids increase. 74 Shabnam Mousavi. MRI Technologist
  • 68. Trauma • MR spectroscopy is not routinely used in the acute setting of head injuries • when the patient has stabilized, MRS is helpful to assess the degree of neuronal injury and predict patient outcomes • 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 75 Shabnam Mousavi. MRI Technologist
  • 69. Infectious disease • Brain abscesses destroy or displace brain tissue, so NAA is not present • The voxel should include the abscess cavity to detect the breakdown products of these lesions • Lactate, cytosolic acid, alanine, and acetate are characteristic metabolites in bacterial abscesses • Toxoplasmosis and tuberculomas show prominent peaks from lactate and lipids 76 Shabnam Mousavi. MRI Technologist
  • 70. Key points  High Cho - High tumor cell density & high vascular proliferation  Low Cho and elevation of lipids – Necrosis  Cho higher enhancing rim -may be the faster growing side of the tumor  Normal Cho and slightly decreased NAA- Vasogenic edema 78 Shabnam Mousavi. MRI Technologist
  • 72. 80  A 50 y M with fever, headache and Lt hemiparesis 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 Shabnam Mousavi. MRI Technologist
  • 73. 81  A 67 YR M WITH POSTERIOR FOSSA SOL 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 Shabnam Mousavi. MRI Technologist
  • 74. 82  Serial MR spectroscopic data from a 25-year-old lady who was under 6 monthly imaging follow-up for a low-grade glioma Shabnam Mousavi. MRI Technologist
  • 75. 83  A 48 Y F WITH HEADACHE AND LEFT HEMIPARESIS 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 Shabnam Mousavi. MRI Technologist
  • 76. 84  A 27 Y M WITH MULTIPLE NODULAR LESIONS IN BRAIN 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 Shabnam Mousavi. MRI Technologist
  • 77. 85  A 14 Y M WITH REFRACTORY CPS PLANNED FOR SURGERY •MRS of Left anterior hippocampus showed smaller NAA peak (33% less) compared to Right indicating a left temporal seizure focus Shabnam Mousavi. MRI Technologist
  • 78. 86  A 48YR F WITH PROVEN GLIOBLASTOMA MULTIFORME TREATED WITH SURGERY, EXTERNAL BEAM RADIATION AND INTERSTITIAL BRACHYTHERAPY. 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) Shabnam Mousavi. MRI Technologist
  • 79. 87  76 Y M PRESENTED WITH RECENT MEMORY LOSS Proton MRS in hippocampal region shows MI peak, decreased NAA and elevated MI/Cr ratio •Dx - Alzheimer’s Disease Shabnam Mousavi. MRI Technologist
  • 80. 88  Patient with known diagnosis of MELAS with new onset of visual symptoms. (Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) MR spectroscopy (TE=144 ms) from the right occipital abnormality shows an inverted doublet at 1.3 ppm (arrows) consistent with a lactate peak. Shabnam Mousavi. MRI Technologist
  • 81. 89  7 MONTH INFANT WITH DELAYED MILESTONES & SPASTICITY MRS show markedly raised NAA peak as compared to control subject Dx – Canavan’s disease Shabnam Mousavi. MRI Technologist
  • 82. 90 • 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. Canavan disease Shabnam Mousavi. MRI Technologist
  • 83. 91  5 Y CHILD WITH SEIZURES 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 Shabnam Mousavi. MRI Technologist
  • 84. 92 • Ischemic stroke- appearance of lactate peak within minutes of ischemia. In chronic phase NAA is suppressed • Multiple sclerosis- Increased Cho due to active demylination. Lipid and Lac may also rise. Presence of MI suggests severe demylination • Hepatic encephalopathy-: increased glutamate, decreased myoinositol • Phenylketonuria- increased Phenylalanine peak at 7.3ppm • AIDS dementia- increased MI and Gln detected. MRS may help in detection of subclinical disease, opportunistic infections and monitoring ART MRS IN OTHER CONDITIONS Shabnam Mousavi. MRI Technologist
  • 85. 94 • 135 TE • Inv Of AA,0.9 ppm, Lac, 1.33 ppm, and Ala, 1.47 ppm peaks • Pyogenic abscess Case report Shabnam Mousavi. MRI Technologist
  • 86. 95 • STEAM • TE 35, only Lip and Lac at 1.3 ppm. • TE 135 spectrum, phase reversal & reduction in signal • Tuberculous abscesses Case report Shabnam Mousavi. MRI Technologist
  • 87. 96 • TE 135 proton MR spectrum from core of lesion – inverted AA and Lac peaks • Multiple signal (*) at 3.6–3.8 ppm • Fungal abscess Case report Shabnam Mousavi. MRI Technologist
  • 88. 97 • MRS with TE 35 - Lac at 1.33 ppm, acetate at 1.92 ppm, and succinate at 2.4 ppm • At TE 135 - Lac and Ala at 1.5 ppm show phase reversal while Ace and Suc show normal phase • Hydatid cyst: Case report Shabnam Mousavi. MRI Technologist
  • 89. 98 Multiple sclerosis • Long TE spectra in acute and chronic MS lesions. – Both - Elevated Cho and reduced NAA – Only acute lesion - Elevated lactate • Short TE spectra from acute lesion and normal brain for comparison – Increased mI, choline, and lipids, slightly decreased Cr and NAA. Case report Shabnam Mousavi. MRI Technologist
  • 91. Whole brain MRS analysis Metabolic parametric maps RECENT ADVANCES 100 Shabnam Mousavi. MRI Technologist
  • 92. • Breast spectroscopy GluCEST(Chemical exchange saturaton transfer MRS) 101 RECENT ADVANCES Shabnam Mousavi. MRI Technologist
  • 93. Prostate MRS Liver MRS to see Fat fraction 102 RECENT ADVANCES Shabnam Mousavi. MRI Technologist
  • 94. FUNCTIONAL MRS 103  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 fMRS and PET Shabnam Mousavi. MRI Technologist
  • 95. CLINICAL APPLICATIONS OF MRS: 104 Shabnam Mousavi. MRI Technologist
  • 96. Conclusion  Proton MRS of the brain is useful whenever biochemical or metabolic assessment may be necessary, such as in differential diagnosis of focal brain lesions  Diagnosis , grading of tumors and response to treatment and follow-up radiation therapy for patients with brain neoplasms  Direct the surgeon to the most metabolically active part of the tumor for biopsy to obtain accurate grading of the malignancy  Diagnosis and prognosis of brain ischemic and traumatic lesions  Assessment of epilepsy and demyelinating diseases  Biochemical alterations in hepatic encephalopathies and neuropediatric affections such as brain tumors, inborn errors of metabolism and hypoxic encephalopathy 105 Shabnam Mousavi. MRI Technologist
  • 97. Conclusion  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 106 Shabnam Mousavi. MRI Technologist
  • 98. Conclusion  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  They require interpretation and should always be correlated with the MR images before making a final diagnosis 107 Shabnam Mousavi. MRI Technologist
  • 99. 108  Handbook of instrumental techniques for analytical chemistry, Settle F, ch 17.  MR spectroscopy in metabolic disorders of the brain, Yilmaz U, Radiologe 2017 Jun;57(6):438-442.  Magnetic resonance spectroscopy: basics. Bluml S. 2013 XIV (402-416)  Proton Mr Spectroscopy, Fundamental Physics and Clinical Applications, Kemal Arda et al, Austin oncology 2016  MR spectroscopy and spectroscopic imaging of the brain. Zhu H, Barker PB. Methods Mol Biol. 2011;711:203–226.  Proton Magnetic Resonance Spectroscopy: Technique for the Neuroradiologist. Kim M Cecil, Neuroimaging clin N Am.2013; 23(3): 381-392.  In vivo magnetic resonance spectroscopy: basic methodology and clinical applications. Marinette van der graff. Eur biophys J. 2010 Mar; 39(4): 527–540. References Shabnam Mousavi. MRI Technologist
  • 100. 109 Shabnam Mousavi. MRI Technologist
  • 101. 110 Shabnam Mousavi. MRI Technologist
  • 103. • N-Acetyl aspertate 2.02 • N-Acetyl aspertate glutamate 2.05 • Choline containing compound 3.22 • Creatine containing compound 3.02 • Myo-inositol 3.56 • Glucose 3.55 • Glutamate/ glutamine 2-2.5, 3.4-3.7 • Lipid 1.3 • Lactate 1.3 • Alanine 1.48 Major spectral peaks assigned in human brain proton spectra from white matter 112 Shabnam Mousavi. MRI Technologist
  • 104. 113  A patient with right HS • Short TE (35msec) spectra at 3T obtained in the left and right hippocampal formation 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 Shabnam Mousavi. MRI Technologist
  • 105. Single Volume MRS MRS TECHNIQUES 114 Shabnam Mousavi. MRI Technologist
  • 106. 115 Inborn errors of metabolism • Canavan and Salla disease show an elevated NAA • Maple syrup urine disease -Branched-chain amino acids at 0.9 ppm. • Phenylketonuria -Small phenylalanine signal at 7.36ppm (i.e. downfield of water) • Non-ketotic hyperglycinemia -Glycine at 3.55 ppm (use long TE to distinguish from mI) Case report Shabnam Mousavi. MRI Technologist
  • 107. 116 Canavan’s disease- AR • Deficiency of aspartoacylase an enzyme that deacetylates NAA, Increased free acetate • Hypotonia and macrocephaly • Symmetrical confluent subcortical WM T2 prolongation & Centripetal spread • Bilateral involvement of globi pallidi, thalami, cerebellum and brainstem Case report Shabnam Mousavi. MRI Technologist
  • 108. 117 OTHER CONDITIONS: Hepatic encephalopathy: increased glutamate, decreased myoinositol Phenylketonuria: increased Phenylalanine peak at 7.3ppm Parkinson’s disease Motor neuron disease Psychiatric disease Shabnam Mousavi. MRI Technologist
  • 109. 118 • Neuronal dysfunction & cell death • Metabolite changes in idiopathic Parkinson’s disease are inconsistent • Multiple system atrophy -reduction in NAA and NAA/Cr ratio when compared with IPD • Lactate increased in Huntington’s disease. Neurodegenerative diseases Shabnam Mousavi. MRI Technologist
  • 110. 119  Proton MRS of the brain is useful whenever biochemical or metabolic assessment may be necessary, such as in differential diagnosis of focal brain lesions  Diagnosis , grading of tumors and response to treatment and follow-up radiation therapy for patients with brain neoplasms  Direct the surgeon to the most metabolically active part of the tumor for biopsy to obtain accurate grading of the malignancy  Diagnosis and prognosis of brain ischemic and traumatic lesions  Assessment of epilepsy and demyelinating diseases  Biochemical alterations in hepatic encephalopathies and neuropediatric affections such as brain tumors, inborn errors of metabolism and hypoxic encephalopathy Shabnam Mousavi. MRI Technologist

Editor's Notes

  1. (MRS), also known as nuclear magnetic resonance (NMR) spectroscopy to study metabolic changes in diseases Got nobel prize in 1952
  2. Basic physics of MRS
  3. پروتون ها در کمیکال های مختلف فرکانس ام آرهای مختلفی دارند
  4. 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.
  5. MRI scan of brain or spine
  6. There are two methods of proton magnetic resonance spectroscopy: single voxel and  multivoxel, with or without spectroscopic imaging.
  7. MR SPECTROSCOPIC IMAGING/MULTI-VOXEL 6-12min
  8. Multi voxels: Variable voxel sizes • More than one lesion • Control from normal
  9. Correct the inhomogeneity of the magnetic field by tuning different pulses in the x, y, and z directions. Usually automated but can be performed manually
  10. STEAM: susceptible on motion PRESS: no affected by motion
  11. از مهمترین پارامتر تکنیکای جمع آوری تصویر
  12. با استفاده از یه مقاله اهمیت پلیسمنت رو بیشتر خدمتتون توضیح میدم
  13. شروع با اینTR & TE are important parameters NAV: 64
  14. Quantitation of taurine (Tau) concentrations with proton MRS 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
  15. 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
  16. با توجه به نکات تکنیکی که گفتیم حالا چطور طیف بهینه به دست بیاریم
  17. It represents how many types of protons are present in the molecule. There are two types of protons.1.Equivqlent 2.Non equivalent
  18. Cho - Cell membrane turn over • Cr - Energy marker -Reference Lactate - Anerobic state (NOT SEEN IN NORMAL BRAIN)
  19. this angle was used with STEAM spectra from the brain. Neurosurgeon, Hunter Sheldon, at Huntington Medical Research Institutes. Instead of doing complex ratios and analysis of the spectra, he simply used his pocket comb. He placed his comb on the spectrum at approximately a 45 angle and connected several of the peaks Gray matter has more cr
  20. Myo-Inositol(synthesized in glial cells) از هم پاشیدگی
  21. Outer volume saturation bands (hatched) surround the 2D-CSI defined volume of interest
  22. 1) 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) Include the leukodystrophies, mitochondrial disorders, and enzyme defects that cause an absence or accumulation of metabolites Soooo Understood by identifying important metabolites and quantifying them. • Comparing with normal and benign tissues, we can understand metabolite markers and grade them.
  23. Outgrow: bozorgtr shodan Pic1: High grade glial tumors
  24. Prognosis • High Creatine levels in grade II gliomas- malignant transformation and poor survival • High Cho -Pediatric brain tumors
  25. عود تومور
  26. • Elevated in rim; N –Around - Metz •Detection of peptides and amino acids in Short TE(rim)
  27. از کار افتادگی breakdown
  28. هرچقدر کاهش ن ای ای وسیعتر بشه ...
  29. 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
  30. ضایعه فضا گیر space occuping 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
  31. 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
  32. A, Coronal contrast-enhanced T1-weighted MR image shows a large right temporal mass with rich contrast uptake with extensive midline shift.
  33. 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
  34. complex partial seizure Conventional MRI revealed no apparent abnormality.
  35. 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
  36. •T1W image shows reduction in the volume of the hippocampus.
  37. (A) 1.5T brain MRI demonstrates areas of T2 hyperintensity and (B) abnormal restricted diffusion, likely related to stroke-like areas of cytotoxic edema. MELAS is the acronym for Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes. MELAS is a form of dementia. It is caused by mutations in the genetic material (DNA) in the mitochondria
  38. T 1W– diffuse hypointensity of supratentorial white matter.  T2W -diffuse hyperintensity of supratentorial white matter انقباض عضلات و مشکل در راه افتادن
  39. Inborn errors of metabolism • Deficiency of aspartoacylase an enzyme that deacetylates NAA, Increased free acetate • Hypotonia and macrocephaly • Symmetrical confluent subcortical WM T2 prolongation & Centripetal spread • Bilateral involvement of globi pallidi, thalami, cerebellum and brainstem
  40. A – T 2 W- hyperintense left occipital region.
  41. Multiple system atrophy -reduction in NAA and NAA/Cr ratio when compared with IPD • Lactate increased in Huntington’s disease.
  42. Plaque(acute o chronic)
  43. Focal brain lesions (neoplastic and non-neoplastic diseases) demyelinating diseases such as multiple sclerosis and leukodystrophy
  44. (MRS) is non invasive means of characterising the tissue.  Multi-voxel technique more complex but accurate  MRS highly sensitive but sometimes non specific  MRS is to be reported in conjunction with conventional MR
  45. hippocampal sclerosis