Role of Magnetic Resonance Spectroscopy (MRS) in Pediatric Neuro-imaging
Husain H Naser, Eoghan Laffan, Manohar Shroff*, Monica Rebollo Polo, Hazar Tabban, and Julie Hurteau-Miller
Children's Hospital of Eastern Ontario, Ottawa and *the Hospital for Sick Children, Toronto, Ontario, Canada
METABOLITES
INTRODUCTION
Magnetic Resonance Spectroscopy(MRS) has become an important clinical tool in children with a wide variety of
neurological abnormalities. MRS differs from standard imaging in that it identifies the chemical composition of a
tissue rather than the anatomic appearance. This poster will illustrate the use of MRS in pediatric neuroimaging,
particularly in patients with brain tumors, hypoxic ischemic injury and metabolic diseases
NEOPLASM
Table 2: Most common metabolites found in MRS of human brain, their meaning and main pathologies .
Remarks
Increased ()
Decreased ()
N acetyl aspartate and N-acetyl aspartyl glutamate (NAA) Peaks 2.0; 2.5 &2.6 ppm
What is MR spectroscopy ?
Echo Time
 A method using the Nuclear Magnetic Resonance
phenomenon to identify the chemical state of various
elements without having to acquire a tissue sample.
 It provides information about the chemical composition of
tissues and any changes in metabolic activity, which may
occur with disease processes.
 The basic principle is that the atomic nuclei are
surrounded by a cloud of electrons, which very slightly
shield the nucleus from any external magnetic field.
 As the structure of the electron cloud is specific to an
individual molecule or compound, the magnitude of this
screening effect is also a characteristic of the chemical
environment of individual nuclei.
 The electron cloud alters the resonance frequency of
elements, which is also determined by the externally
applied magnetic field.
 The change or shift in resonance frequency, caused by
the electron cloud, causes a chemical shift, which is
specific for each molecule. This chemical shift is
independent of the strength of the external magnetic
field.
 Chemical shift is measured by expressing it in parts per
million (ppm) of the resonance frequency, relative to a
standard resonance frequency (usually H2O).
 MRS determines the relative concentration of each
molecule/resonance frequency and expresses it in an MR
spectrum or graph.
 The X-axis of the spectrum represents the chemical shift
/ resonance frequency in ppm and the Y-axis represent
the relative concentration of each molecule (Fig. 1C+D).
 The peaks in MRS spectrum are relative concentrations of
the metabolites and do not represent absolute figures.
• Information from MRS depends on the
repetition time (TR) and time to echo (TE).
• Short TE=30-35 and intermediate TE=144 are
the two routinely used values.
• The routine metabolites identified with short
and long TE include: N-acetyle aspertate (NAA),
Creatine (Cr), Choline (Cho), and Lactate (Lac)
whenever present.
• Additional metabolites identified only with short
TE include: Lipids (Lip), Myo-inositol (mI),
Glutamine and Glutamate (GLx).
• Because Lip and Lac resonate approximately in
the same frequency range, the Lac peak is
identified by:
a. Presence of double peaks or doublet with a
7-Hz difference between the 2 peaks.
b. Using TE=144ms, the Lac peak inverts
below the baseline
c. Using TE (270-288ms) the Lip signal have
no manageable signal and only Lac is
observed
Technical Consideration
•There are 2 basic methods used to sample a
given volume in MRS: (a) Stimulated echo
acquisition mode (STEAM) and (b) Point-resolved
spectroscopy (PRESS).
•PRESS is the most widely used technique
nowadays due to better signal-to-noise ratio.
• 2nd most abundant free amino
acid in the brain, after
glutamate.
• Synthesized in mitochondria.
• Exclusively localized to neurons,
• It can be found in cell culture of
oligodendroglia, but not in
mature glial cells.
• Markedly elevated NAA
pathognomonic for Canavan
disease.
• Increases during neuronal
maturation.
• Disorders that impair neuronal
number and density, impair
neuronal function or displaces
neurons.
• Almost any brain insult.
• Hyperosmolarity.
•
•
•
•
Creatine deficiency syndromes.
Stroke.
Various Tumors.
Trauma.
Choline compounds (Cho), Peak 3.2 ppm
• Linked to cell membrane
metabolism.
•
•
•
•
Tumor, trauma.
Encephalitis, any inflammation.
Demyelination.
In normal neonates.
•
•
•
•
Toxoplasmosis.
Hepatic disease.
Hepatic encephalopathy.
Hyponatremia.
Single Voxel MRS (SVS)
•
•
•
•
•
•
Multivoxel MRS (MVS)
2x2x2cm (8cc) voxel is routinely used.
Smaller sample can be selected for small lesions.
Main limitation is restricted anatomical coverage.
Appropriate voxel positioning is critical, to avoid
susceptibility artifacts, such as the ventricles or
prominent sulci.
•
•
•
Also called chemical shift imaging (CSI), allows
simultaneous coverage of multiple voxels.
Provides a 2D study of a slice or 3D assessment of a
given volume.
Evaluates lesion extent and acquires spectra within
contralateral or unaffected parenchyma for
comparison.
For both techniques, MR scanner employs a process called shimming to improve magnetic field homogeneity
and subsequently narrow peak linewidths.
Higher order shimming is required for MVS in order to obtain uniform fields in multiple voxels.
• Most common intracranial neoplasm in
children >2 years of age.
• Typically exhibits elevated lipids, lactate
and Cho, decreased levels of NAA, Cr and
mI, suggesting an aggressive and
hypermetabolic neoplasm.
• MRS findings are often contradicted by the
benign clinical course typical of this tumor.
• Many JPS characterized by multiple cysts.
• Voxel position should maximize sampling to
solid portion of the tumor.
Myo-inositol, Myo-inositol monophospate and glycine (mI), peaks 3.5 & 4.1 ppm
• Glial marker located in astrocytes.
• Absent in neurons.
• Gliosis.
• Tuberous sclerosis, cortical
dysplasia .
• MS, leukodystrophy.
• Pick disease.
• Tumors.
• Hyponatremia.
• Encephalopathy (hepatic and
neonatal).
• Infarction.
Glutamine, glutamate (Glx) 2.2-2.6 ppm
Gamma-aminobutyric acid (GABA), & Aspartate 3.6-3.8 ppm
• Glutamate is a neurotransmitter,
most abundant amino acid in the
human brain
• Primarily found in astrocytes
•
•
•
•
Any destructive neuronal process.
Encephalitis.
Meningitis.
Reye’s syndrome.
•Elevated in variety of tumors,
along with lactate and alanine.
Cho
Cr
•Head injury.
•Hyponatremia.
•Hypoxic ischemic injury, Infarction.
•MS.
•Aggressive neoplasm.
• Figure 2, A&B: 15-year-old female with cerebellar JPA.
• B: MRS at TE=144ms shows elevated Cho and Lac
(doublet below baseline) with significant decrease in
NAA.
A
•
•
•
•
Cho
Medulloblastoma
Cr
B
C
• Figure 1, A: MV MRS, at TE=35 obtained with 14x10 cm area
from a single slice.
• B: CSI and relative ratio of metabolites in each voxel.
• C: MRS of one of the voxels from the same study.
• D: SV MR spectrum at TE= 35ms, demonstrates the metabolites
of a typical spectrum. Creatine 1st peak (Cr), Myo-inositol (mI),
Choline (Cho), Creatine 2nd peak (Cr), Glutamine and Glutamate
(GLx), N-Acetyl Aspartate (NAA) and Lipid (Lip) peaks shown.
A
D
The peaks in the MRS spectra represent the relative concentrations of the metabolites in the brain.
Cr is used as internal reference as it is the most stable metabolite in the human brain.
Simple ratios using Cr signal as a reference can be reported (NAA/CR, Cho/Cr, and mI/Cr)
In conditions associated with disruption of Cr concentration (e.g. trauma, stroke), a reference voxel in a
visually normal region with similar gray and white matter composition (usually the contralateral hemisphere)
can be sampled and compared with the voxel in the affected region.
• Absolute metabolite concentration and semi-quantitative analysis are being reported from some academic
institutions.
•
•
•
•
Patients
with DD
Control
Subjects
NAA/Cr
2.14 ± 0.10
2.53
2.06 ± 0.29
2.44
Cho/Cr
1.65 ± 0.22
1.37
1.76 ± 0.23
1.36
NAA
TEMPLATE DESIGN © 2008
www.PosterPresentations.com
P value
± 0.15
± 0.21
<.001
<.017
± 0.19
± 0.14
<.024
<.002
A
B
C
B
A
• Figure 12: 11-year-old with X-linked
adrenoleukodystrophy. A: Axial T2 shows symmetrical
high signal intensity in the peritrigonal region.
• B: MRS at TE=144ms shows elevated Cho and
reduced NAA.
B
D
B
A
A
• Figure 13: 6-year-old boy presented with
delayed development and diagnosed with
creatine deficiency after MRS.
• A: Axial FLAIR show no obvious abnormality.
• B: MRS at TE=144ms of the frontal white
matter (WM) shows low creatine peak.
B
• Figure 14: 3-month-old male with Canavan disease.
• A: Axial T2 shows diffuse white matter (WM)
disease also involving the subcortical WM.
• B: MRS of the frontal WM at TE=35ms shows NAA
elevation above all other metabolites. Elevation of
mI is consistent with gliosis.
D
LACTATE & PROPANE-1,2-DIOL
• Figure (4) 5-year-old boy with left thalamic astrocytoma.
• A: Axial T1-weighted imaging post-Gad. B: MRS at TE=144ms showed elevated Cho and reduced NAA.
• C &D: Follow-up study 9 month later, after surgery and chemotherapy, shows small residual tumor. MRS of
the residual lesion (D) shows similar pattern to the original tumor.
B
• Figure 5, A: 5-year-old boy with atypical rhabdoid
tumor in the left Cerebellopontine angle.
• B: MRS of the lesion at TE=35ms shows
markedly elevated Cho and no NAA, indicating
absence of neural tissue. Cr is also markedly
reduced
• Propane-1,2-diol is a solvent used in IV anticonvulsants.
• MRS appearance is nearly identical to lactate doublet,
peak at 1.1 ppm.
• Care must be taken when analysing peaks between 1.0
and 1.4 ppm, in order not to confuse this doublet with
Lac.
• Figure 15: MRS at TE=35ms of frontal white matter at of
neonate aged 9-minths show both lactate and propane1,2-diol (PD)
C
• Figure 9: 13-month-old female, suspected non accidental injury.
• A, B & C: Bilateral basal ganglia, frontal and occipital lobe
ischemia and bilateral scalp hematomas.
• D: MRS at TE=35ms in the left basal ganglia shows large lactate
doublet above the baseline.
D
Lac
PD
CONCLUSION
Abscess
B
A
• Characteristic MRS pattern is observed inside
an abscess, helping to differentiate it from
cystic tumors.
• Cytosolic amino acids (0.9ppm) found only
inside abscesses, but not in necrotic tumors,
with 100% specificity.
• Acetate (1.92ppm) & Succinate (2.4ppm) are
also highly specific for abscesses.
• Lac, lipid, & Alanine (1.4ppm) may be seen.
• NAA, Cho & Cr not seen unless MRS
contribution from surrounding parenchyma.
Cho
NAA
• Figure 6, A: 12 year old boy with metastatic
malignant melanoma in the left occipital lobe.
• B: MR spectroscopy at TE=144ms demonstrates
large lactate peak below baseline, an elevated
Cho and decreased NAA.
A
Leukoencephalopathies
Lac
NAA
• Figure 2: 5-year-old girl with developmental delay,
unknown cause. A: Voxel position.
• B: MRS at TE=35ms: Reduced NAA/Cr ratio (2.07)
relative to the age matched normal ratio (table 3).
C
B
Figure 8: 9-year-old female with meningoencephalitis.
A&B: DWI and ADC map shows area of restricted diffusion in the right cerebellar hemisphere posteriorly
D: MRS at TE=35ms shows elevated lactate doublet, reduced NAA and Cho.
C: Sample site of MRS.
•
•
•
•
Cho
SWM: subcortical white matter, DD: developmental delay. Data are the mean ± standard
deviation.
Cr
• We use PRESS in all cases. We use TE=35ms in the frontal white matter and basal ganglia for developmental
delay. We use a TE=144 for tumors, ischemia and to detect Lac.
• Figure 11: 5-year-old female with Glutaric aciduria type II
• B: MRS of the frontal white matter (LT) at TE=144ms shows
inverted lactate doublet and reduced NAA.
mI
A
Table 3: MRS ratios of patients with developmental delay older
than 2 years and compared to normal population (2)
Cho
MRS Protocol
B
B
NAA
Qualitative versus quantitative analysis
Frontal SWM
Parieto-occipital SWM
A
Lac
Cho
Frontal SWM
Parieto-occipital SWM
D
Figure 7: 2-day-old baby boy with history of perinatal hypoxia and seizures.
DWI(A) and ADC map(b) shows areas of restricted diffusion in both occipital lobes.
D: MRS at TE=144ms from the area of signal abnormality shows Lac doublet below baseline.
C: Sample site of MRS.
A
Ratio in Voxel
• Heterogeneous group of syndromes
characterized by defect in mitochondrial
function due to enzymatic deficiencies.
• Lactic acidosis within the blood, serum, CSF,
brain and muscles is a common feature.
• MRS can be useful in measuring brain Lac in
these processes.
• However the distribution, extent and degree
of involvement will influence the detection of
Lac.
• Figure 3A: 4-year-old girl with medulloblastoma.
• MRS at TE=144ms shows markedly elevated Cho and
reduced NAA.
• Stroke.
• High grade tumors,
• Abscess.
• The NAA/Cr ratio increases rapidly from 1 month
of age up to 1 - 2 years.
• In infants, the Cho/Cr is higher than that of adults.
• The Cho/Cr ratio declines rapidly from 1 month of
age up to 1 year, then declines more slowly until
2 years.
• Diminished NAA/Cr ratio is found in patents with
developmental delay older than 2 years. The
abnormal MRS resembles that of healthy children
much younger than 2 years (Fig. 2).
• This is hypothesized as hypomyelination.
C
Mitochondrial disorders
NAA
NORMAL AND DELAYED DEVELOPMENT
A
B
METABOLIC DISORDERS
• A variety of metabolic diseases characterized by
progressive destruction of the white matter
including:
• Disorders of lysosomal function (e.g. metachromatic
leukodystrophy MLC).
• Disorders of peroxismal function (e.g. X-linked
adrenoleukodystrophy).
• Less well understood disorders includes Canavan,
Alexander, and Cockayne syndrome.
• MRS can be useful in diagnosing Canavan disease
from other leukodystrophies as it is the only
confirmed condition where NAA signal is significantly
elevated, often x4-6 times age matched normals.
• Children with Alexander disease and MLC cannot be
distinguished from other leukodystrophies by MRS
alone.
B
A
Lactate (Lac) 1.3 ppm
•Endpoint of anaerobic glycolysis.
• Cerebral hypoxia, ischemia and frank infarction are more common in children than is generally appreciated.
• Diffusion weighted imaging (DWI) has provided a window into the earliest stage of ischemic injury. In many
pediatric patients with ischemia, imaging is outside the timeframe in which DWI is useful. MRS can play a role
here.
• In Acute ischemia:
• Lac should appear elevated and may be accompanied by increase in glutamate and lipid.
• The remaining metabolites (NAA, Cr, Co, mI) may remain within normal limits.
• In the subacute setting:
• The glutamate will continue to rise.
• Lac clearance will depend on the level of perfusion. Lac is detectable for up to 3 weeks from the insult.
• Macrophage activity may produce Lac in subacute and chronic stages.
• In the weeks after the injury, tissues may demonstrate decrease NAA and potentially diminished Cr, with
elevated Cho.
• It is important to note that equivalent reduction of NAA and Cr resonance will result in a normal NAA/Cr ratio
despite significant tissue damage.
• Elevation of Lac and decrease in NAA also are demonstrated by MRS in cases of neonatal asphyxia.
• Lactate peak can be found normally in preterm neonates. Comparison with the spectra of the age matched
normal's can be helpful in determining which Lac levels are beyond normal limits.
Lac
• Most common pediatric CNS malignancy.
• Most common primary posterior fossa
tumor in children.
• MRS demonstrates marked elevation of
Cho and decrease of NAA.
• The degree of elevation of the Cho/NAA
ratio, glycine and mI are larger when
compared with astrocytomas .
Lipids (Lip) Peaks 0.8 and 1.3 ppm, macromolecular proteins 0.9 & 2.05 ppm
Table1: MRS can be performed by singe voxel (SV) or multivoxel (MV) technique
• MRS can provide metabolic confirmation of a neoplasm.
• Reveals the characteristics of cellular turnover, anaerobic metabolism and overall cellular energy.
• May be useful to sample multiple regions within a heterogeneous tumor in order to assess more accurately the
metabolic characteristics of each component.
• Increased Cho indicates a growing tumor with significant cell membrane turnover.
• NAA is diminished by displacement of neuronal tiisue or infiltration of the tumor.
• Elevated lactate peak reflects anaerobic metabolism.
• MRS is not well correlated with the tumor grade in the pediatric population (2).
Juvenile Pilocytic Astrocytoma
(JPA)
Creatine and Phosphocreatine (Cr) peaks 3 & 3.9 ppm
• Involved in regulation and
storage of cellular energy
metabolism.
• Marker of overall cellular density.
INFARCTION, HYPOXIA AND ISCHEMIA
Lac
A
B
MRS is an essential MRI sequence in pediatric neuroimaging, detecting changes at the metabolic level. The
pediatric radiologist should be aware of normal spectral tracings, changes that occur during development and
the significance of abnormal peaks and ratios in a variety of neurological conditions.
References:
B
A
• Figure 10: 8 year old boy with brain abscess in left
frontal lobe with ring enhancement (A) and
peripheral rim of low signal intensity edema.
c
• B+C: MRS at TE=144ms in abscess cavity shows
inverted Lac, alanine (Ala) and cytosolic amino acids
(AA) and elevated succinate (Suc) and acetate (Ac).
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8. http://www.chem.ucalgary.ca/courses/351/Carey/Ch13/ch13-nmr-1.html. Chapter 13: Spectroscopy