Magnetic Resonance Spectroscopic Imaging Study Research Articles

Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: a magnetic resonance spectroscopic imaging study in rat brain.

The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three different time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by injection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional 1H magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-acetyl-aspartate (NAA) was determined. To analyze the chances of metabolic tissue recovery, the outcome of treatment, defined by a reversal of lactate concentration, was compared with the lactate intensity before treatment. In untreated animals (n = 4), clot embolism resulted in a drop of perfusion signal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observation period. Thrombolysis partially restored blood flow, but the mean lactate concentration decreased only slightly after successful lysis in animals treated 1.5 hours after embolism. If treatment was initiated later, no decline of lactate level was observed. Five hours after initiation of thrombolysis, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/- 60% of the early ischemic value (40 minutes after embolization) if treatment began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In individual pixels, the probability of metabolic tissue recovery clearly declined with increasing lactate concentration before thrombolysis. Interestingly, this probability was independent of treatment delay, but the number of pixels with low lactate declined with increasing ischemia time. Potential clinical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.

Ketosis and epilepsy: 31P spectroscopic imaging at 4.1 T.

To determine whether changes in the high-energy phosphates occur with use of the ketogenic diet in patients with intractable epilepsy. 31P magnetic resonance spectroscopic imaging studies were performed at 4.1 T in seven patients with intractable epilepsy (four Lennox-Gastaut syndrome, one absence, one primary generalized tonic-clonic, and one partial complex) before and after institution of the ketogenic diet. Coronal 1H anatomic imaging also was performed to provide correlation to the 31P data. Taking the patients as a group, the ratio of phosphocreatine (PC)/gamma-adenosine triphosphate (ATP) measured at baseline (regular diet) compared with that measured after the ketogenic diet showed a small but significant increase from 0.61+/-0.08 to 0.69+/-0.08 (p < 0.05). Comparing the ratio of PCr inorganic phosphorus (Pi) measured at baseline with the postketogenic diet, there was a significant increase from 2.45+/-0.27 to 2.99+/-0.44 (p < 0.05). As a group, improvement of energy metabolism occurs with use of the ketogenic diet. This is in agreement with the chronic ketosis studies performed earlier in rodents.

Metabolite changes in neonatal rat brain during and after cerebral hypoxia‐ischemia: a magnetic resonance spectroscopic imaging study

Metabolite changes in neonatal rat brain during and after cerebral hypoxia‐ischemia: a magnetic resonance spectroscopic imaging study

Metabolite changes in neonatal rat brain during and after cerebral hypoxia-ischemia: a magnetic resonance spectroscopic imaging study.

Cerebral metabolite concentrations were measured in infant rats using proton magnetic resonance spectroscopic imaging. Measurements were made prior to, during and after exposure of rats (6- and 7-day-old) to unilateral cerebral hypoxia-ischemia (right carotid artery occlusion +2h 8% oxygen). Data clustered according to age and outcome-6-day-old animals with no infarct and 7-day-old animals with infarct. In 6-day-old animals, cerebral lactate concentration increased during hypoxia-ischemia, particularly ipsilateral to the occlusion, and returned to normal soon after the end of hypoxia. There were no major changes in N-acetyl-aspartate levels (NAA) in this group and no regions of hyperintensity on T2 or DW weighted images at 24 h. In the 7-day-old animals, lactate increased during hypoxia-ischemia and remained elevated in the first hour after reperfusion. Furthermore, lactate remained at 258+/-117% and 233+/-56% of pre-hypoxic levels, 24 and 48 h post-hypoxia, respectively. NAA concentrations ipsilateral to the occlusion decreased to 55+/-14% during hypoxia, recovered early post-hypoxia and again decreased to 61+/-25% and 41+/-28% at 24 and 48 h post-hypoxia-ischemia, respectively. The infarct volumes measured by diffusion weighted and T2 weighted MRI at 48 h post-hypoxia were 152+/-40 mm3 and 172+/-35 mm3, respectively. Thus, irreversible damage correlated well with measured in vivo lactate and NAA changes. Those animals in which NAA was unaltered and lactate recovered soon after hypoxia did not show long-term damage (6-day-old animals), whereas those animals in which NAA decreased and lactate remained elevated went on to infarction (7-day-old animals).

Pediatric low-grade gliomas: prognosis with proton magnetic resonance spectroscopic imaging.

Our aim was to assess the correlation between the low-grade glioma (LGG) metabolic profile and tumor progression. Using in vivo proton magnetic resonance spectroscopic imaging, we specifically asked whether and which metabolic features are associated with tumor regrowth or recurrence. Eleven pediatric patients with histologically proven partially resected (<20% resection) midline LGG were treated and followed up for a period of 2 years. All patients underwent proton magnetic resonance spectroscopic imaging studies before any management was determined. Tumor progression was defined as radiological evidence of mass enlargement (>25%) during the follow-up period. Proton magnetic resonance spectroscopic imaging was performed using a PRESS-CSI sequence on a General Electric 1.5-tesla scanner (General Electric Medical System, Waukesha, WI). The signal intensities of N-acetylaspartate, choline (CHO), and creatine from the tumor and the normal brain were used to calculate normalized metabolite intensities and metabolite ratios. Tumors that progressed during a 2-year period displayed higher normalized CHO than those that remained stable (Mann-Whitney test, P < 0.03). The majority (five of six) of the rapidly growing LGG showed values of normalized CHO of at least 1, whereas the nonprogressors had a normalized CHO value of less than 1. In association with pediatric LGG, high normalized CHO values seem to herald the potential for rapid tumor growth. These observations may be valuable for defining subsets of patients with LGG who may benefit from early therapeutic interventions.

Spectroscopic imaging of frontal neuronal dysfunction in hyperekplexia.

We used proton magnetic resonance spectroscopic imaging (MRSI) to assess in vivo cortical neuronal involvement in hyperekplexia. Cerebral neuronal function was measured using proton MRSI in four unrelated patients with hyperekplexia and 20 healthy controls. All patients had the major form of hyperekplexia, with additional atypical clinical features in two of them. Family history was positive in three patients and absent in one. The neuronal marker N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) were measured in frontal, central and parietal areas. The MRSI showed a reduction of the relative resonance intensity of NAA/(Cr + Cho) in frontal and central regions in three patients, and in the right frontal region of the fourth. In one patient a second MRSI showed normal relative NAA resonance intensities over both temporal lobes as well as in the brainstem. In two subjects the topography of EEG abnormalities in the frontal lobes coincided with the MRSI findings. This proton MRSI study indicates the presence of frontal neuronal dysfunction in hyperekplexia. Whether this represents cortical dysfunction or an epiphenomenon of diencephalic or brainstem abnormalities remains open. However, the observation of normal proton MRSI in the temporal regions and brainstem in one of the patients seems to concur with the hypothesis of a facilitatory role of cortical dysfunction within areas of sensorimotor representation in the generation of the pathological startle reaction in hyperekplexia.

Regionally Specific Neuronal Pathology in Untreated Patients with Schizophrenia: A Proton Magnetic Resonance Spectroscopic Imaging Study

Background: Proton magnetic resonance spectroscopic imaging ( 1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. Methods: We studied 12 medication-free patients, 5 of whom were “drug naive” and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. Results: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. Conclusions: Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.

In-plane motion correction for MR spectroscopic imaging.

A motion-detection method is described that is specifically suited for MR spectroscopic imaging (MRSI) studies. Information on in-plane rotation and translation of the subject was obtained using external spatial reference markers that are uniquely identified via their chemical shift. The marker locations were obtained directly from the acquired data at each encoding step, and no additional data acquisition was required. This method was applied to brain 1H MRSI studies that include subcutaneous lipid signals, which otherwise result in enhanced sensitivity to subject motion.

Neuronal metabolic dysfunction in patients with cortical developmental malformations: a proton magnetic resonance spectroscopic imaging study.

Cortical developmental malformations are best diagnosed by MRI and are often the cause of refractory epilepsy. Little is known about the metabolic cell function on MR spectroscopy of these types of brain anomaly. We studied 23 patients with cortical developmental malformations and refractory epilepsy using proton MR spectroscopic imaging. Mean age was 28 years (range, 9 to 47 years). The lesions examined were focal cortical dysplasia (n = 5), heterotopia (four band, six periventricular, two subcortical), polymicrogyria (n = 3), tuberous sclerosis (n = 2), and polymicrogyria and periventricular nodular heterotopia (n = 1). We measured the relative signal intensity of N-acetylaspartate/creatine (NAA/Cr) in the lesion, in the perilesional region, and in the region remote from the visible lesion. The values were compared with those from similar brain regions of 25 normal control subjects. The mean NAA/Cr z score values for the 23 patients were as follows: lesion, -2.20 +/- 0.32 (mean +/- SE), n = 21; perilesional region, -1.01 +/- 0.38, n = 15; and distant region, -0.03 +/- 0.34, n = 18 (p < 0.0002). Despite the presence of a large number of neurons, heterotopia showed a relative decrease of NAA in some patients, suggesting that the neurons present were dysfunctional. The maximal NAA/Cr decrease, indicating metabolic dysfunction, colocalized to the structural malformation as defined by MRI and extended to normal-appearing regions adjacent to the visible lesion.

Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis.

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study.

Focal brain damage occurring early in development can have widespread repercussions throughout the developing brain. In living adult rhesus monkeys, we studied the long-term effects of early mesial temporo-limbic (MTL) lesions on prefrontal cortex (PFC) neurons using proton magnetic resonance spectroscopic imaging (1H-MRSI), an in vivo neurochemical assay technique for measuring signals from metabolites such as N-acetyl-aspartate (NAA, a neuronal marker), choline-containing compounds (CHO) and creatine + phosphocreatine (CRE). Six monkeys (NL) had undergone surgical ablation of MTL structures within 3 weeks of birth, six monkeys received the same lesion at approximately 5 years of age and six monkeys were normal controls. We found significant bilateral reductions of NAA relative signals exclusively in the PFC of the NL group in comparison with either of the other groups. Our results indicate that neonatal MTL damage specifically affects PFC neurons of adult monkeys as indicated by a reduction of NAA. The basis of this effect involves developmental processes as implicated by two arguments: analogous damage during adulthood does not have the same effect; NAA in the healthy brain increases during development. This finding may have implications for understanding developmental aspects of prefrontal-temporolimbic connectivity, and the reduction of NAA levels observed in prefrontal cortex of patients with schizophrenia.

Increased choline signal coinciding with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopy imaging study

The authors tested the hypothesis that proton magnetic resonance spectroscopic (1H-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of low- to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with 1H-MRS imaging over a period of 3.5 years. At the time of each 1H-MRS imaging study, clinical examination, MR imaging, positron emission tomography with 18F-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having either stable or progressive disease. Measures of the percentage changes in the choline (Cho) 1H-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms.

Increased choline signal coinciding with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopy imaging study.

The authors tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of low- to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with 1H-MRS imaging over a period of 3.5 years. At the time of each 1H-MRS imaging study, clinical examination, MR imaging, positron emission tomography with 18F-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having either stable or progressive disease. Measures of the percentage changes in the choline (Cho) 1H-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms.

Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder.

This study aimed to evaluate aspects of second messenger function in the brain of suicide victims and patients with bipolar disorder. Inositol and its synthetic enzyme, inositol monophosphatase, were measured in postmortem brain samples of 10 suicide victims, eight patients with bipolar affective disorder, and 10 normal comparison subjects. The frontal cortex inositol levels of the suicide victims and the patients with bipolar disorder were significantly less than those of the normal comparison group. No differences in cerebellum or occipital cortex inositol levels were found among the three groups. The groups also showed no differences in inositol monophosphatase activity in any brain area. These results could suggest a deficiency of second messenger precursor in patients with bipolar disorder and suicide victims.

Blunted left cingulate activation in mood disorder subjects during a response interference task (the Stroop)

Functional neuroimaging studies have found abnormal anterior cingulate activity in depressed subjects, and other studies have shown that the cingulate gyrus becomes active in healthy subjects during interference tasks. The authors hypothesized that subjects with mood disorder might show blunted cingulate activation during the standard Stroop interference task or during a modified version involving sadness-laden words. In contrast to 11 age- and sex-matched healthy control subjects who activated the left cingulate during the standard Stroop, 11 mood-disordered subjects activated the right anterior cingulate gyrus only slightly and instead showed increased activity in the left dorsolateral prefrontal and visual cortex. This study supports theories of blunted limbic and paralimbic activation and abnormal cingulate activity in depression and adds to the growing knowledge of the functional neuroanatomy of depression.

Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: A 31Phosphorous magnetic resonance spectroscopic imaging study

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP. There were no asymmetries of temporal lobe phosphorous metabolites in the control group. In addition, both left temporal PCr and the degree of asymmetry of temporal lobe PCr were highly correlated with the thinking disturbance subscale of the BPRS. This study provides further support for temporal lobe metabolic asymmetry in schizophrenia and its possible association with clinical symptoms.

Re-establishment of cerebral metabolism after carotid endarterectomy

The purpose of this study was to evaluate the metabolic changes that occur in the human brain in patients with a symptomatic carotid artery stenosis. N-acetyl-aspartate (NAA), choline, creatine and lactate were measured both before, and 4 days after, carotid endarterectomy, by magnetic resonance spectroscopic imaging (MRSI). Eight controls and 16 patients were examined. MRI and MRSI studies were performed on a Philips Gyroscan S15 whole body system operating at 1.5 Tesla. 1H spectra were selected from regions in the centrum semi-ovale outside areas showing white matter hyper intensities on MRI. All patients showed a decrease of the NAA/choline and NAA/creatine ratio in the symptomatic hemisphere compared to the contralateral hemisphere and also compared to the controls. Lactate was present in some patients (5/16). After endarterectomy, the NAA/choline and NAA/creatine ratios increased significantly compared to the ratios preoperative. Lactate was absent or more than 50% reduced after the operation. MRSI showed metabolic changes in areas of the brain that did not show any abnormalities on MRI. There are marked changes in brain metabolism in the symptomatic hemisphere of patients with a severe carotid artery stenosis. These metabolic changes normalise four days after endarterectomy.

Reduced phase encoding in spectroscopic imaging

The effect of different spatial-encoding (k-space) sampling distributions are evaluated for magnetic resonance spectroscopic imaging (MRSI) using Fourier reconstruction. Previously, most MRSI studies have used square or cubic k-space functions, symmetrically distributed. These studies examine the conventional k-space distribution with spherical distribution, and 1/2 k-space acquisition, using computer simulation studies of the MRSI acquisition for three spatial dimensions and experimental results. Results compare the spatial response function, Gibbs ringing effects, and signal contamination for different spatial-encoding distribution functions. Results indicate that spherical encoding, in comparison with cubic encoding, results in a modest improvement of the response function with approximately equivalent spatial resolution for the same acquisition time. For spin-echo acquired data, reduced acquisition times can readily be obtained using 1/2 k-space methods, with a concomitant reduction in signal to noise ratio.

Human brain infarction: proton MR spectroscopy.

Two-dimensional proton magnetic resonance (MR) spectroscopic imaging studies were performed of the distributions of the major hydrogen-1 metabolites of choline, creatine, N-acetyl aspartate (NAA) and lactate in normal (n = 6) and subacutely to chronically infarcted (n = 10) human brain. The two dimensions of phase encoding were applied over a 20-mm-thick section of brain tissue that had been selected with a double spin-echo localization method. Normal brain showed bilaterally symmetric metabolite distributions and no detectable lactate. Nine of 10 studies of brain infarction showed substantial decreases in NAA, creatine, and choline in the infarcted area compared with control areas; averaged for all studies, the decreases were 77% +/- 8, 63% +/- 11, and 54% +/- 12, respectively (mean +/- standard error). The decreased metabolite concentrations are probably due primarily to diminished cell density in the infarct. The decrease in NAA was larger than the decreases in choline and creatine. Findings in all of the studies showed lactate in the infarcted tissue and/or ventricles. The continued presence of lactate in the infarct indicates increased anaerobic glycolysis due to ischemia or other factors.