Serial Proton Magnetic Resonance Spectroscopy Research Articles

Glutamatergic Response to Heat Pain Stress in Schizophrenia.

Regulation of stress response involves top-down mechanisms of the frontal-limbic glutamatergic system. As schizophrenia is associated with glutamatergic abnormalities, we hypothesized that schizophrenia patients may have abnormal glutamatergic reactivity within the dorsal anterior cingulate cortex (dACC), a key region involved in perception of and reaction to stress. To test this, we developed a somatic stress paradigm involving pseudorandom application of safe but painfully hot stimuli to the forearm of participants while they were undergoing serial proton magnetic resonance spectroscopy to measure changes in glutamate and glutamine levels in the dACC. This paradigm was tested in a sample of 21 healthy controls and 23 patients with schizophrenia. Across groups, glutamate levels significantly decreased following exposure to thermal pain, while ratio of glutamine to glutamate significantly increased. However, schizophrenia patients exhibited an initial increase in glutamate levels during challenge that was significantly different from controls, after controlling for heat pain tolerance. Furthermore, in patients, the acute glutamate response was positively correlated with childhood trauma (r = .41, P = .050) and inversely correlated with working memory (r = -.49, P = .023). These results provide preliminary evidence for abnormal glutamatergic response to stress in schizophrenia patients, which may point toward novel approaches to understanding how stress contributes to the illness.

Serial proton magnetic resonance spectroscopy of normal-appearing gray and white matter in MS

<h3>Abstract</h3> For more than a century researchers have been comparing embryogenesis and regeneration hoping that lessons learned from embryonic development will unlock hidden regenerative potential. This problem has historically been a difficult one to investigate since the best regenerative model systems are poor embryonic models and vice versa. Recently however, the comparison of embryogenesis and regeneration has seen renewed interest as emerging models including the sea anemone <i>Nematostella vectensis</i> have allowed researchers to investigate these processes in the same organism. This interest has been further fueled by the advent of high-throughput transcriptomic analyses that provide virtual mountains of data. Unfortunately much of this data remains in raw unanalyzed formats that are difficult to access or browse. Here we present <b><i>N</i></b><i>ematostella</i><b><i>v</i></b><i>ectensis</i><b>E</b>mbryogenesis and <b>R</b>egeneration <b>T</b>ranscriptomi<b>cs</b> - NvERTx, the first platform for comparing gene expression during embryogenesis and regeneration. NvERTx is comprised of close to 50 RNAseq datasets spanning embryogenesis and regeneration in <i>Nematostella</i>. These data were used to perform a robust <i>de novo</i> transcriptome assembly which users can search, BLAST and plot expression of multiple genes during these two developmental processes. The site is also home to the results of gene clustering analyses, to further mine the data and identify groups of co-expressed genes. The site can be accessed at http://nvertx.kahikai.org.

Loss of Neuronal Integrity during Progressive HIV-1 Infection of Humanized Mice

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin, and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity after HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration.

Dynamics of Metabolic Changes in Intracranial Metastases and Distant Normal-Appearing Brain Tissue after Stereotactic Radiosurgery: A Serial Proton Magnetic Resonance Spectroscopy Study

The present study evaluated the dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain after stereotactic radiosurgery (SRS). Forty neoplasms were evaluated with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) both before and after treatment. From one to six examinations (median, 3) were done in each individual case during follow-up. At the time of each investigation additional (1)H-MRS was obtained from the normal-appearing brain distant from the radiosurgical target. Investigated metabolites included N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr), and mobile lipids (Lip). Within the first month after SRS responded tumors showed a statistically significant increase in NAA/Cho ratio, and decrease of Cho content and Lip-to-normal brain Cr (nCr) ratio. By contrast, statistically significant metabolic alterations were not detected in stabilized tumors. Statistically significant volumetric and metabolic changes were not marked between three and 12 months after treatment in non-progressing lesions. Alternatively, decrease of NAA/Cho ratio, NAA content and Cr content, and increase in Lip/nCr ratio and Cho content were evident in progressive neoplasms, and subtle metabolic alterations could be revealed even before the increase in the lesion volume. Metabolic characteristics of normal-appearing brain distant from the radiosurgical target did not show statistically significant changes within the first year after treatment. In conclusion, additional use of serial (1)H-MRS during follow-up after SRS for intracranial metastases permits detailed evaluation of the metabolic tumor response and may be potentially helpful for early prediction of recurrence.

1247 POSTER Alterations of brain metabolism after therapy of paediatric brain tumors. a serial proton magnetic resonance spectroscopy study

1247 POSTER Alterations of brain metabolism after therapy of paediatric brain tumors. a serial proton magnetic resonance spectroscopy study

Intérêt de la spectroscopie par résonance magnétique dans la sclérose concentrique de Balo

Balo's concentric sclerosis is a neuropathological type of multiple sclerosis characterized by alternating rings of spared myelin and demyelination. Diagnosis is based on MRI, but very few data are available concerning the lesion features using serial proton magnetic resonance spectroscopy (1H-MRS). We report 1H-MRS initial findings and disease course in one case of Balo's concentric sclerosis. The first 1H-MRS study of 2 concentric ring-enhanced lesions showed a decreased N-acetyl-aspartate (NAA) peak, an increased choline peak, 2 broad lactate peaks and the presence of a lipid peak at 0.9 ppm. Six months later, 1H-MRS showed a decrease of choline peak, whereas the lactate peak had disappeared. The NAA peak was still at a low level. These findings are similar to those reported in demyelinating disorders, such as multiple sclerosis. Thus, in Balo's concentric sclerosis, 1H-MRS may provide neurochemical arguments for inflammation and demyelination, and indicate the severity of axonal damage and recovery.

Early metabolic changes in metastatic brain tumors after Gamma Knife radiosurgery:1H-MRS study

Evaluation of early metabolic changes in metastatic brain tumors after Gamma Knife radiosurgery was performed by long-echo (TR, 2000ms; TE, 136ms; 128-236 acquisitions) volume-selected single-voxel proton magnetic resonance spectroscopy (MRS). Eighty-five brain metastases in 81 patients were investigated before treatment and 16-18h thereafter. Standard metabolic ratios, namely N-acetylaspartate (NAA)/creatine (Cr), phosphorylcholine/glycerophosphorylcholine (Cho)/Cr, NAA/Cho, lactate (Lac)/Cr, and mobile lipids (Lip)/Cr, were calculated, and comparison of their values before and after irradiation was done. No volumetric changes of any neoplasm were found in any case on the next day after treatment. At the same time, significant reduction of Cho/Cr (P < 0.001) and NAA/Cr (P < 0.01) ratios on the proton MRS of the tumor was disclosed. Reduction of Cho/Cr ratio was significantly more prominent in neoplasms with higher pretreatment Cho/Cr ratios (P < 0.001) and heterogeneous contrast enhancement (P < 0.01). Reduction of NAA/Cr ratio was predominantly determined by its pretreatment value (P < 0.001). The observed decrease of Cho/Cr ratio probably reflects inhibition of proliferative activity and early apoptotic cell loss, whereas reduction of NAA/Cr may result from radiation-induced modulation of neuronal activity in the peritumoral brain tissue. Serial proton MRS represents a valuable diagnostic tool for evaluation of metabolic changes in intracranial neoplasms after radiosurgical treatment.

Serial proton magnetic resonance spectroscopy of the brain in children undergoing cardiac surgery

We used proton magnetic resonance spectroscopy to study 11 children (age < 8 years) with congenital heart disease undergoing cardiopulmonary bypass to determine whether low (10 ± 4; n = 6) vs high (20 ± 4; n = 5) perfusate hematocrits during bypass resulted in changes in brain metabolites which correlate with neurologic injury. Long and short echo time single voxel magnetic resonance spectroscopy in occipital gray matter and neurologic assessment were performed preoperatively and 2 and 5 days postoperatively. We also determined whether prolonged periods at low flow rates during bypass affected spectroscopy variables. We found no significant differences in metabolite ratios between the low vs high hematocrit groups or the lower vs higher flow rate groups (repeated measures analysis of variance of observation ranks converted to normal scores). However, our study was limited by statistical power due to the small sample size, therefore no conclusions could be made. Additional studies involving a greater number of patients are necessary. In all 11 children, magnetic resonance spectroscopy detected a significant decrease in brain N-acetyl-aspartate, and increases in myoinositol and glutamate/glutamine after surgery (Quade test) demonstrating that magnetic resonance spectroscopy is sensitive in detecting subtle postoperative changes in brain metabolites.

Serial proton magnetic resonance spectroscopy in lesions of Balò concentric sclerosis.

Balò concentric sclerosis is a rare demyelinating disorder. Serial proton magnetic resonance spectroscopic (1H-MRS) studies were carried out to better understand the biochemical changes within concentric lesions. Five concentric lesions in four patients with Balò concentric sclerosis were chosen as the objects of serial observation. They included two early acute lesions (showing as concentric ring enhancement on magnetic resonance imaging (MRI) after gadolinium administration), two late acute lesions (showing as marginal enhancement on MRI), and one early subacute lesion (showing as edematous concentric lesions without enhancement on MRI). The duration of follow-up ranged from 2-23 months (mean 10 months). A total of 20 1H-MRS studies were performed. On each 1H-MRS study, short-echo (30 ms) and long-echo (136 ms) spectra were obtained. The peaks of N-acetyl-asparate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), lactate, and mobile lipid were observed and compared. Generally, a decrease of NAA/Cr ratio and an increase of Cho/Cr ratio were seen on all the spectra. Observing longitudinally, a trend of decreasing NAA/Cr ratio first and then partially recovering later was noted. The lowest level of NAA/Cr ratio was noted at the late acute stage or early subacute stage. The Cho/Cr ratio and amplitude of the lactate peak showed a similar trend as that of NAA/Cr, but in an opposite direction. It was rising first and descending later. The highest levels of Cho/Cr ratio and lactate peak were also observed at the late acute or early subacute stage. In addition, lactate peaks could be detected as long as 7 months after onset of symptoms. Lipid metabolite (two broad peaks at 0.9-1.5 ppm) was seen at the initial study of each group, but fluctuated in size on follow-up. The characteristic biochemical changes of concentric sclerosis were a decreased NAA/Cr ratio, an increased Cho/Cr ratio, two broad peaks at 0.9-1.5 ppm, lactate production, and a reversible NAA/Cr ratio on follow-up. The serial 1H-MRS studies revealed a strong biochemical association between NAA, Cho, and lactate, which may be caused by the same pathogenetic process of demyelination and inflammatory cellular infiltration. The specificity of the serial changes may provide information about the stage of the concentric lesion and perhaps aid in monitoring progression of concentric lesions and evaluating therapy.

Clinical studies on three cases of the interval form of carbon monoxide poisoning: serial proton magnetic resonance spectroscopy as a prognostic predictor

Three patients with the interval form of carbon monoxide (CO) poisoning were studied for associations between their clinical courses and serial changes on: (1) MRI; (2) EEG; (3) single photon emission computed tomography with N-isopropyl- p-[ 123I]iodoamphetamine ([ 123I]IMP SPECT); and (4) proton magnetic resonance spectroscopy ([ 1H]MRS) to evaluate their usefulness as prognostic predictors. A hyperintense area on MRI T 2-weighted images and a hypointense area on T 1-weighted images, appearing in the deep white matter, persisted for a prolonged period even after improvement of the clinical symptoms, and did not become an accurate indicator of clinical evaluation or prognosis. [ 1H]MRS studies with the volume of interest set in the frontal lobe white matter revealed increases in choline-containing compounds, and reductions of N-acetylaspartate in all cases. These findings normalized in one subclinical case over time. Distinctive findings in the severe cases included increased lactate in two cases showing akinetic mutism, with a difference in prognosis noted according to the degree and period of persistence of this increase. EEG findings were relatively well correlated with clinical symptoms in the early period, with a good correlation no longer consistent after a certain period was exceeded. [ 123I]IMP SPECT findings did not always reflect clinical symptomatology either. These results indicate that [ 1H]MRS is the most useful indicator in the clinical evaluation of patients with the interval form of CO poisoning.

Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: relation between time from onset, neurological deficit, metabolite abnormalities in the infarct, blood flow, and clinical outcome.

Proton magnetic resonance spectroscopy (MRS) can be used to study metabolite abnormalities in the brains of stroke patients. We have used it to examine the relations between the metabolites in the infarct (N-acetylaspartate [NAA] and lactate) and the time lapse from stroke to MRS, the presenting neurological deficit, infarct size and swelling (on MRI), blood flow to the infarct (estimated by transcranial Doppler ultrasound), and clinical outcome. Patients with symptoms of a moderate to large cortical infarct underwent serial proton MRS (Siemens 1.5 Magnetom) within 4 days, from 5 to 10, and from 11 to 35 days after the stroke. A long echo time PRESS single voxel or chemical shift imaging acquisition was used. Transcranial Doppler ultrasound was performed daily in the first week and twice per week thereafter until the final MRS. Clinical features and baseline demographic data were collected independently by a stroke physician and 6-month outcome by postal questionnaire. Fifty patients underwent at least 1 MRS examination. Reduced NAA in the infarct within the first 4 days was related to the clinical stroke syndrome, more extensive infarction, more severely reduced blood supply to the infarct, and the presence of lactate. The presence of lactate was related to large infarcts and reduced NAA. Swelling in the infarct was most closely associated with large infarcts and reduced blood supply but not reduced NAA or the presence of lactate. Clinical outcome was most closely related to the extent of the infarct (more than to the clinical syndrome)--the larger the infarct the worse the outcome--but not to the metabolite concentrations alone. The reduction in NAA (but not the presence of lactate) in a visible infarct was related to the reduction in blood flow to the infarct, which in turn was related to infarct extent and clinical outcome.

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.

Serial proton magnetic resonance spectroscopy in a patient with acute carbon monoxide poisoning

Serial proton magnetic resonance spectroscopy in a patient with acute carbon monoxide poisoning

Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions.

Serial proton magnetic resonance spectroscopy (MRS), was carried out at 1-2 monthly intervals on eight patients with multiple sclerosis who presented with evidence of a large acute cerebral white matter lesion. An MRS was obtained from acute lesions (volumes of interest 4-12 ml), which at presentation showed gadolinium-diethylenetriamine penta-acetic acid enhancement, and from similar volumes of normal appearing white matter lateral to the lesion and nearer the scalp. Follow-up ranged from 4 to 9 months (mean 6 months). Short echo spectra from acute enhancing lesions invariably showed the presence of large resonances at 0.9 and 1.3 p.p.m. compared with normal appearing white matter and healthy age matched controls, indicating that these peaks were not the result of voxel contamination from scalp fat. These resonances, which probably represent lipid products of myelin breakdown, were detected in lesions which had been enhancing for < 1 month and remained elevated for a mean of 5 months (range 4-8 months). The results provide evidence that short echo proton MRS can detect myelin breakdown products and that myelin breakdown occurs during the initial inflammatory stage of lesion development. The ratio of N-acetylaspartate (NAA) (a neuronal marker) relative to creatine was reduced in acute lesions and in normal appearing white matter. In six of the lesions studied there was, however, a subsequent rise in the NAA/creatine ratio indicating that axonal loss is not the only mechanism of reduction in the NAA/creatine ratio.

Serial Proton Magnetic Resonance Spectroscopy of Ischemic Brain Injury in Humans

Four patients were observed serially with 1H magnetic resonance spectroscopy (MRS) at times ranging from 3 days to 10 weeks after a documented ischemic event. Spectra were obtained from 8 cc volumes in infarcted regions and contralateral matched normal regions. Reproducible variations in n-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and the sequential changes in lactate and lipid resonances are related to the pathophysiology of stroke. A conspicuous lack of significant change in the choline (Cho) resonance with concomitant decrease in NAA and Cr + PCr is reported as a possible marker of ischemic injury.