Proton magnetic resonance spectroscopy in brain white matter disorders

The advent of magnetic resonance imaging (MRI) has revolutionized the clinical approach to the evaluation of brain white matter disorders and has contributed significantly to expansion of the concept of these diseases. MRI is very sensitive at detecting white matter lesions, but conventional T1 and T2-weighted images do not provide specific pathological information about the lesions, and correlation between MRI lesion load and clinical disability is often weak. Proton magnetic resonance spectroscopy can provide chemical-pathological information of a given tissue invivo. The use of this MR technique in brain white matter disorders has shown to improve diagnostic classification and to provide surrogate measures useful for monitoring disease evolution and response to therapeutic intervention.The study was supported in part by grants from the Multiple Sclerosis Society of Canada and from the Progetto Sclerosi Multipla of the Istituto Superiore di Sanità, Rome, Italy.     

Proton magnetic resonance spectroscopy in parkinson's disease and atypical parkinsonian disorders

Proton magnetic resonance spectroscopy (¹H-MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple-system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age matched controls. The study assessed the level of N-acetylaspartate (NAA), creatine–phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. ¹H-MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.     

Proton magnetic resonance spectroscopy of cerebral lactate and other metabolites in stroke patients.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six. METHODS: One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec. RESULTS: All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. N-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in N-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct. CONCLUSIONS: Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future.     

Proton magnetic resonance spectroscopy study of dyskinesia patients.

Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (-13%, P = 0.020) and SOD patients (-12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (-11%, P = 0.079). All other metabolite ratios (N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction.     

Proton magnetic resonance spectroscopy of the autistic brain

To evaluate brain dysfunction in autism, proton magnetic resonance spectroscopy (1H-MRS) was performed for 29 autistic patients (5-15 y.o.) and 19 normal children (6-14 y.o.). We obtained magnetic resonance (MR) spectra of the left and right amygdaloid-hippocampal regions and the left cerebellar hemisphere with a STEAM sequence (TR = 5000 ms, TE = 18 ms). In addition to the evaluation of signal intensity ratios, the absolute concentration of three major metabolites (N-acetylaspartate [NAA], creatine/phosphocreatine [Cr] and choline-containing substances [Cho]) was quantified by an internal reference method using unsuppressed tissue water. Although no abnormal MR images were found in the three regions examined, the signal intensity and the concentration of NAA in the left amygdaloid-hippocampal region and the left cerebellar hemisphere were reduced significantly in autistic patients compared to normal children. We speculated that this decrease in NAA reflected neuronal loss, immaturity or hypofunction in these regions. The results of our study were in agreement with those of previous studies on autism, one by neuropathological methods and the other using a single photon emission computed tomography with 99mTc HMPAO. Disorders of the amygdaloid-hippocampal region and cerebellum are considered to play an important role in the characteristic cognitive and emotional dysfunction in autism. 1H-MRS is a valuable tool to clarify the pathophysiology of autism.     

Proton magnetic resonance spectroscopy in frontotemporal dementia

This study of frontotemporal dementia (FTD) was carried out to determine whether MR spectroscopy can provide an in vivo marker for the neuronal loss and gliosis that occur in this condition. We compared spectra in frontal and temporal regions known to be affected early in the course of the disease with spectra in the parietal lobe that is spared until late stages of FTD. We were interested in the relative concentrations of two compounds, NAA (a marker of neuronal integrity) and mI (a marker of gliosis), expressed as ratios to creatine (a relatively stable brain constituent). MR spectroscopy was performed on the temporal, parietal, and anterior cingulate cortices of five patients with the established semantic dementia form of FTD, two patients with the frontal form of FTD and 13 age matched controls. Structural MRI and neuropsychometry were also performed. Patients with FTD had reduced NAA/Cr in frontal and temporal, but not parietal lobes. The two patients with the frontal form of FTD had increased mI/Cr in their cingulate cortices. These data show for the first time that MR spectroscopy can reveal regionally selective abnormalities in patients with FTD. This opens up the possibility of using MR spectroscopy as a clinical tool to identify earlier presentations of the condition.     

Proton magnetic resonance spectroscopy in Kennedy syndrome

OBJECTIVE: To seek regional metabolite abnormalities in patients with Kennedy disease (KD) using proton magnetic resonance spectroscopy. DESIGN: Nine patients with KD showing the typical phenotype without clinical signs of upper motor neuron involvement were compared with 17 male, age-matched, healthy control subjects. Relative metabolite concentrations for N-acetyl (NA) groups, choline-containing groups (Cho), phosphocreatine (Cr), and lactate (Lac) were determined in the brainstem and the motor region. RESULTS: Pathologic Lac signals suggesting impaired energy metabolism were absent in patients and controls. In the brainstem area, patients with KD showed a significant reduction in the NA/Cho metabolite ratio (P = .01). In the motor region, NA/Cho (P = .04) and NA/Cr (P = .03) ratios were significantly reduced. The reduction of the NA/Cho ratio in the motor region mainly resulted from decreased metabolite ratios in 3 patients. Changes in metabolite ratios did not correlate with the number of trinucleotide cytosine-adenine-guanine repeats from leukocytes. Because of the relatively small sample size due to the rarity of KD, these results should be considered preliminary. CONCLUSIONS: Spectroscopic data fail to provide further evidence for altered energy metabolism in KD. Metabolite changes in the brainstem indicate a reduction of the neuronal marker NA or elevated Cho. These findings may reflect neuronal loss or gliosis consistent with the known pathologic features. In a subset of patients, altered metabolite ratios best explained by neuronal loss suggest subclinical involvement of the motor region. The extent of metabolite changes does not correlate with the trinucleotide repeat length.     

Proton magnetic resonance spectroscopy in multiple sclerosis

Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.     

1H and 31P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders.

Proton and phosphorus magnetic resonance spectroscopy of the brain was performed in 35 patients with degenerative cerebral disorders: 24 patients had demyelinating (white matter) disorders and 11 patients had neuronal (gray matter) disorders. Four grades of demyelination and three grades of cerebral atrophy were distinguished by magnetic resonance imaging criteria. The spectroscopic data were compared with normal values previously obtained. With increasing degrees of demyelination, lower ratios of phosphodiesters to beta-ATP were found. This trend was statistically significant. Decreased phosphodiester-beta-ATP ratios occurred simultaneously with imaging abnormalities. The decrease in phosphodiester-beta-ATP ratio in demyelinated areas is attributed to white matter rarefaction. Increasing cerebral atrophy was accompanied by lower ratios of N-acetyl aspartate to creatine. This trend was statistically significant. The decrease in the N-acetyl aspartate-creatine ratio was demonstrated before the magnetic resonance images showed signs of cerebral atrophy in patients with neuronal disorders. As N-acetyl aspartate is located exclusively in neurons and their branches, a decrease of the N-acetyl aspartate-creatine ratio can be attributed to neuronal and axonal damage and loss.     

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.     

Proton magnetic resonance spectroscopy of patients with parkinsonism

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.     

Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients.

Water-suppressed 1H magnetic resonance spectra were recorded from two brain regions of psychiatric patients and normal volunteers. The two regions studied were (a) the basal ganglia structures surrounding the anterior horn of the lateral ventricle and (b) the occipital cortex. N-Acetylaspartate (NAA), phosphocreatine-creatine (PCr-Cr), choline and inositol resonances were seen in both regions. Ratios of metabolite peak integrals to PCr-Cr peak integral were calculated for each spectrum. To control for partial volume effects, comparisons between patients and controls were made only from identical regions i.e. basal ganglia vs basal ganglia, and likewise for occipital cortex. Metabolite ratios from the occipital region of patients were similar to those from the occipital region of normal subjects. Bipolar patients being treated with lithium had elevated NAA/PCr-Cr in the basal ganglia region when compared to normals. These patients also demonstrated elevated choline/PCr-Cr and inositol/PCr-Cr ratios in the basal ganglia region.     

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.     

Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis.

We are investigating the potential of in vivo proton magnetic resonance spectroscopy for noninvasive characterization of the chemical pathology of plaques in magnetic resonance brain images from patients with multiple sclerosis. Spectra localized to chronic, irreversible plaques showed a decrease in the ratio of N-acetyl/creatine resonance intensities relative to normal-appearing white matter. Spectra localized to active plaques showed different metabolite changes as compared with spectra from identical, plaque-free volumes in the contralateral hemispheres. Some active plaques showed either no abnormalities or only an increase in tissue lactate. Spectra from others showed an increased ratio of choline/creatine resonance intensities, with or without a decreased N-acetyl/creatine resonance intensity ratio. In one case, serial observations showed an evolution of changes in spectra from a single plaque from an increased choline/creatine ratio to a decreased N-acetyl/creatine ratio. These observations suggest that proton magnetic resonance spectroscopy may be able to distinguish acute or active from chronic plaques and to characterize the pathologic evolution of active plaques by measurement of local tissue metabolite levels.     

Proton magnetic resonance spectroscopy in childhood brainstem lesions

Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information regarding cell membrane proliferation, neuronal damage, and energy metabolism. Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions located at the brainstem using Point-resolved spectroscopy sequences. Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up. Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role.     

Proton magnetic resonance spectroscopy of the human brain in schizophrenia

In vivo proton magnetic resonance spectroscopy (1H MRS) has been utilized by neuroimaging laboratories in recent years to reliably measure compounds such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and to a lesser extent glutamate and glutamine in the human brain. To date, the most consistently replicated findings in schizophrenia are reduced NAA measures in the hippocampal regions. Since NAA is thought to be a neuronal/axonal marker and a measure of neuronal/axonal integrity, hippocampal NAA reductions have been interpreted as strong evidence for neuronal/axonal loss or dysfunction in this brain region. The evidence for neuronal loss or dysfunction based on NAA is less consistent for the frontal cortex and white matter, temporal cortex, basal ganglia, cingulate region, and thalamus in schizophrenia. Furthermore, there are no consistently replicated findings for choline or creatine alterations in any of the brain regions examined in schizophrenia. Finally, significant technical difficulties make reliable measurement of glutamine and glutamate problematic at the present time.     

Proton magnetic resonance spectroscopy in Parkinson''s disease and progressive supranuclear palsy.

OBJECTIVES: Proton magnetic resonance spectroscopy (1H-MRS) localised to the lentiform nucleus, was carried out in eight patients with idiopathic Parkinson's disease and five patients with progressive supranuclear palsy. The aim of the study was to assess the concentration of N-acetyl-aspartate (NAA), creatine and phosphocreatine (Cr), and choline containing compounds (Cho) in the putamen and globus pallidus of these patients. METHODS: Peak ratios obtained from patients were compared with those from nine healthy age matched controls. RESULTS: NAA/Cho and NAA/Cr ratios were reduced significantly in patients with progressive supranuclear palsy. CONCLUSION: These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of these patients. 1H-MRS is a non-invasive technique that can provide useful information concerning striatal neuronal loss in the basal ganglia of patients with parkinsonian syndromes.     

Proton magnetic resonance spectroscopy of brain metabolites in galactosemia

Brain edema may occur in infants with galactosemia and has been associated with accumulation of galactitol. Proton magnetic resonance spectra were obtained from 12 patients (four newly diagnosed neonates and eight patients on galactose-restricted diets, age range 1.7-47 years) and control subjects to measure brain galactitol levels in vivo and correlate them with urinary galactitol excretion. The results demonstrate that a markedly elevated brain galactitol level may be present only in newborn infants with galactosemia who exhibit massive urinary galactitol excretion.