Second, since abnormalities in the brain are often focal, and because brain tissue is heterogeneous, it is necessary to obtain spectra from localized areas, either from single or multiple volumes. Small voxels, on the order of 1 or 2 cm 2 , and long acquisition times produce relatively low signal to noise ratios. Third, the power of using MRS is the possibility to quantify the spectra that are generated. This, however, is not a trivial task. Since absolute quantification is difficult to perform accurately, many laboratories calculate the relative quantity of metabolites present by using the ratio of one metabolite to another that is known to be unchanged.
Resonances in MR spectra are identified primarily by their frequency, ie, position in the spectrum, expressed as the shift in frequency in parts per million ppm relative to a standard.
Water-suppressed, localized proton MR spectra of a healthy human brain at "long" echo times TE commonly, TE, or milliseconds reveal 4 major resonances Figure 1 :. In certain pathological conditions, a methyl resonance from lipids or alanine can also be detected in this region. Changes in the resonance intensity of Cho appear to result mainly from increases in the steady state levels of soluble choline compounds, including choline, phosphocholine, glycerophosphocholine, and, in some cases, betaine.
Choline levels increase in acute demyelinating lesions 2 because these membrane phospholipids are released during active myelin breakdown. Many brain tumors are also associated with high signals from Cho, presumably associated with their increased cellular density. Total Cr concentration is relatively constant throughout the brain and tends to be relatively resistant to change. Therefore, Cr is often used as an internal standard to which the resonance intensities of other metabolites are normalized.
Care must be taken, however, not to use local Cr signals as an internal standard for some destructive pathological processes, such as malignant tumors, which can result in focal decreases of measured Cr. Normal developmental changes in proton spectra have been described. Levels of NAA-Cr increase rapidly in the first few years of life.
However, adult values are not completely attained until 16 years of age. Decreases in the relative NAA concentrations are observed in pathological processes well known to involve neuronal loss such as degenerative disorders, stroke, and glial tumors. Low NAA signals are also observed in other brain pathological processes in which the loss or damage to neurons and axons is less well known and less evident, even at postmortem examination. The ability to quantify neuronal loss or damage in vivo is one of the most important potential applications of MRS in cerebral disorders. Lactate is the end product of glycolysis and accumulates when oxidative metabolism is unable to meet energy requirements.
Certain brain neoplasms can cause increased levels of lactate because they have elevated relative rates of glycolysin. Lactate also accumulates in the extracellular environment of necrotic tissue and fluid-filled cysts. A third circumstance in which lactate levels may be elevated are inflammatory reactions that are associated with cellular infiltrates.
It is thought, for instance, that the prolonged elevation of lactate levels following ischemic infarction results from the metabolism of infiltrating macrophages. Magnetic resonance spectroscopy is a promising method for improving the specificity of noninvasive diagnosis of brain neoplasms.
Figure 2 illustrates the problem with MRI scans from 2 elderly patients who rapidly developed symptoms suggestive of focal cerebral space-occupying lesions. The MRI images demonstrate the presence of lesions but cannot discriminate between the meningioma seen in Figure 2 , A, and the glioblastoma seen in Figure 2 , B. In contrast, by providing chemical profiles of the tumors, proton spectra from the MRS imaging add another dimension by which the space-occupying lesions can be differentiated.
Changes in the intensity of individual resonances are generally not sufficiently specific for diagnostic classification of lesions. Therefore, it is necessary to look at the pattern across multiple resonances.
Magnetic resonance spectroscopy in pediatric neuroradiology: clinical and research applications.
Spectra from the somewhat atypical meningioma seen in Figure 2 , A, show features consistent with the absence of neurons low NAA levels and necrosis high lactate and lipid levels. The spectra also reveal a resonance from alanine. Although alanine may be present in a number of tumor types, it is only clearly visible separate from lactate in vivo in meningiomas. The spectra from this meningioma can be compared with the distinctive metabolic profile of the glioblastoma.
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While the spectrum of the glioblastoma also consists of low NAA, high lactate, and high lipid levels, these resonances occur in different relative proportions to those of the meningioma. In studies with good MRS imaging data, pattern recognition also has been able to identify different grades of gliomas, radiation necrosis, abcesses, and focal lesions in patients with acquired immunodeficiency syndrome AIDS.
Proton MRS also has been used to predict the location of histopathological features important for brain tumor histological diagnosis. Changes in the chemical-pathological profile of spectra also have been used to monitor the response to drug and radiation therapy, and even to predict the response to chemotherapy. It is known that the metabolic demands of a seizure may exceed the capacity of the brain to provide the required energy oxidatively.
The activation of anaerobic glycolysis that results leads to a local accumulation of lactate. Accordingly, in the rare instances when it has been possible to obtain spectra from active seizure foci, the expected increase in the lactate resonance intensity has been observed. In humans, these increases of lactate levels persist for several hours after the seizure.
Many of these patients can be helped by surgical removal of the epileptic focus, provided that 1 all or most of the patient's seizures originate from 1 temporal lobe and 2 the remaining temporal lobe can compensate for the functional loss of the removed side. Lateralization of the seizures has generally been based on clinical and electroencephalographic EEG recordings, which usually include videotelemetry. If surface EEG is unsuccessful, electrodes may need to be placed intracerebrally. This traditional approach is being modified by modern neuroimaging techniques.
Both MRI and positron emission tomography analyses have been used successfully for lateralization of seizure foci, but their results can vary widely between studies. Magnetic resonance spectroscopy detection of decreased NAA levels in one or both temporal lobes Figure 3 compares favorably with these techniques and may be the most sensitive and accurate single method for lateralization of TLE.
- MR spectroscopy of pediatric brain disorders.
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This must mean that the regional decreases in NAA levels detected interictally reflect neuronal dysfunction associated with the epileptic state, rather than irreversible neuronal loss associated with hippocampal sclerosis. The pathology of multiple sclerosis MS is usually described as demyelination with relative preservation of the integrity of the axon shaft. The conduction block resulting from demyelination is traditionally believed to account for the neurologic impairment of MS.
However, measurements of NAA levels with MRS have emphasized that in addition to demyelination, substantial axonal damage does occur in this disease.
MR Spectroscopy of Pediatric Brain Disorders | SpringerLink
Magnetic resonance spectroscopic studies show that concentrations of NAA are substantially reduced within acute MS lesions. Furthermore, these decreases in NAA levels usually show partial recovery over time. Both the decline and the recovery of NAA levels have been found to correlate strongly with alterations in neurologic impairment observed in patients with MS.
These results reinforce the hypothesis that axonal dysfunction is associated with neurologic dysfunction and its subsequent recovery in the acute phase of MS. Although the focus above emphasized alterations of NAA levels, acute lesions also show changes in other metabolites. Large increases in the Cho resonance occur early and are, at least in part, associated with increased mobility and MR visibility of membrane phoshopholipids.
Moderate increases in lactate levels are also observed and probably result from both the presence of inflammatory infiltrates themselves and their effects on local vasculature. Magnetic spectroscopic images show that the Cr signal returns to normal in subacute and chronic plaques.
Short TE spectra show increases in myoinositol 15 and lipids with greater sensitivity than long TE spectra. Preliminary data suggest that increases in lipids detected by MRS may occur before the development of lesions that can be observed using T 2 -weighted MRI. Incomplete recovery of axonal damage in MS eventually leads to the accumulation of irreversible disability. Indeed, it is the reduction of NAA within the normal-appearing white matter that correlates best with the extent of disability of patients with chronic MS.
The ability of MRS to demonstrate metabolic changes that appear to be specific for axonal damage, demyelination, and inflammation may have important implications for measuring the outcome of new treatments for MS. Current treatments are directed primarily at reducing the initial stages of inflammation and do not completely arrest the disease. Future treatments may target the different components of the inflammatory process that result in axonal damage, and that thus far only MRS can measure specifically. Human immunodeficiency virus 1—infected patients are susceptible to a number of neurologic complications.
Later on, cognitive dysfunction develops and MRI may show atrophy and nonspecific white matter changes associated with further reductions in NAA and increases in Cho levels. In the later stages of AIDS, the most common diseases affecting the brain parenchyma are secondary to opportunistic infection or malignancy and are predominantly focal, such as progressive multifocal leukoencephalopathies, cerebral toxoplasmosis, and primary cerebral lymphomas. Magnetic resonance spectroscopy may be able to distinguish between these different space-occupying lesions based on their chemical profiles.
Although the brain can metabolize glucose anaerobically for brief periods in the absence of oxygen, this is done at the expense of the accumulation of lactate. This lactate, or the associated acidosis, may actually exacerbate the extent of neural damage. N -acetylaspartate resonances can be used to estimate the extent of the neuronal damage that occurs, both immediately and in the stages following an acute ischemic event.
A consistent picture that emerges is that within the area of infarcted tissue there is an elevation of levels of lactate and diminished levels of NAA. In the pediatric population, 1 H-MRS has been used to study neonatal hypoxia during delivery, hypoxic encephalopathy following near drowning, and following various other acute insults to the central nervous system, including shaken baby syndrome. Low levels of NAA-Cr ratios and elevated lactate concentrations were consistently demonstrated in the areas of infarction and have been shown to predict adverse neurologic status in both the short and long term.
In the adult population, a similar pattern of low NAA levels and high lactate levels is seen acutely following infarction. Clinically less important and smaller changes in Cho and Cr levels may also occur. Levels of NAA and lactate continue to decline up to a week after the infarct, 21 suggesting that the "window" for salvage of damaged neurons may be greater than expected. These biochemical markers may also provide a surrogate for monitoring therapeutic intervention in the acute stroke period.
Low levels of NAA and high levels of lactate correlate with and predict impaired neurologic function. Preliminary data suggest that 1 H-MRS may be used as a clinical tool for monitoring chronic ischemia as well.
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Therefore, an understanding of normal development of the brain and its circuitry is important for both identifying the causes of psychiatric disorders and for development of effective treatments. N2 - Adolescence, a transitional period between childhood and adulthood years of age , is characterized by maturation of cognitive and behavioral abilities. AB - Adolescence, a transitional period between childhood and adulthood years of age , is characterized by maturation of cognitive and behavioral abilities.
Kennedy Krieger Institute School of Medicine. Abstract Adolescence, a transitional period between childhood and adulthood years of age , is characterized by maturation of cognitive and behavioral abilities. Fingerprint Magnetic resonance spectroscopy. Magnetic Resonance Spectroscopy. Attention Deficit Disorder with Hyperactivity. Infection and Encephalitis. Hepatic Encephalopathy in Children. Magnetic Resonance Spectroscopy in Epilepsy. Jennifer G. Levitt, Jeffry R.
Magnetic Resonance Spectroscopy of the Fetal Brain. Wisnowski, Andre D. Furtado, Niveditha Pinnamaneni, Ashok Panigrahy. Multinuclear MRS in Children. Case Reports. Back Matter Pages About this book Introduction Magnetic resonance spectroscopy MRS is a user-friendly, widely available imaging modality that can be of particular use for brain conditions, including tumors, metabolic disorders, and systemic diseases.