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Biomedical subjects

D J Meyerhoff

Publications and source records attributed to D J Meyerhoff.

At least 19 recordsLinked to original sources
PubMed1996

Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging.

OBJECTIVE: To use 1H magnetic resonance spectroscopic imaging to study differences in neuron density (N-acetylaspartate [NAA]), membrane phospholipid metabolites (choline [Cho]), and creatine-containing metabolites (creatine plus phosphocreatine [Cr]) in subjects with Alzheimer's disease (AD), with subcortical ischemic vascular dementia (SIVD), and elderly controls. DESIGN: Cross-sectional, between groups. SETTING: A Veterans Affairs medical center and university memory clinic. PARTICIPANTS: Forty elderly subjects with AD (n = 14), with SIVD (n = 8), and elderly controls (n = 18). MAIN OUTCOME MEASURES: We used 1H magnetic resonance spectroscopic imaging to acquire spectra from a 80 x 100 x 17-mm volume superior to the lateral ventricles. Spectra were analyzed from voxels in anterior, medial, and posterior gray and white matter using nuclear magnetic resonance-1 and the results were compared between groups using repeated measures analysis of variance (ANOVA), Tukey's test, and individual Student's t tests. RESULTS: Using ANOVA, significantly lower levels of NAA/Cho and NAA/Cr and significantly higher levels of Cho/Cr were observed across both gray and white matter voxels in subjects with AD. Using individual Student's t tests, a significantly lower level of NAA/Cho and a higher level of Cho/Cr were observed in the posterior gray matter in subjects with AD. Using ANOVA in subjects with SIVD, significantly lower gray and white matter NAA/Cr levels were observed. Using Tukey's test, the NAA/Cr level was significantly lower in frontal white matter voxels in subjects with SIVD compared with controls. CONCLUSIONS: Our findings in subjects with AD suggest neuron loss in gray matter, axon loss in white matter, and altered Cho metabolism in posterior brain regions. Our findings in subjects with SIVD are consistent with higher levels of creatine-containing metabolites and/or lower levels of NAA in frontal white matter.

Aged↗
PubMed1996

Alzheimer disease and subcortical ischemic vascular dementia: evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging.

PURPOSE: To determine the association between H-1 magnetic resonance (MR) spectroscopic imaging and MR imaging differences in subjects with Alzheimer disease (AD) or subcortical ischemic vascular dementia (SIVD) versus control subjects and if both studies combined enable discrimination of AD from control subjects better than either study alone. MATERIALS AND METHODS: Measures were obtained in nine AD, eight SIVD, and 11 control subjects with MR imaging segmentation software. RESULTS: Statistically significantly lower N-acetylaspartate/choline-containing metabolites (Cho) and higher Cho/creatine-containing metabolites in posterior mesial gray matter in AD versus control subjects were independent of MR imagining differences. Combined measures allowed correct classification of AD and control subjects, but none of the MR measures allowed accurate discrimination between AD and SIVD subjects. CONCLUSION: Between-group differences in tissue-type contributions to H-1 MR spectroscopic imaging voxels must be accounted for when reporting H-1 MR spectroscopic imaging data in AD, SIVD, and control subjects. Combined studies allowed more accurate discrimination between AD and control subjects than either study alone.

Aged↗
PubMed1995

Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites.

We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter. Chronic alcohol consumption was associated with reduced white matter concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) were associated with reduced concentrations of PDE and PCr, compared with both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV interactions were detected, the effects of HIV infection and alcohol abuse were cumulative. This is reflected in a successive decrease of white matter PDE and PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+ light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations were lower in ARC/AIDS alcoholics than in HIV- light/nondrinking individuals. These findings suggest altered brain phospholipid metabolites and energy metabolites with alcohol abuse and HIV infection. They demonstrate that the adverse metabolic effects of HIV on the brain are augmented by chronic alcohol abuse.

AIDS Dementia Complex↗
PubMed1995

Brain atrophy and cognitive function in older abstinent alcoholic men.

We used computer-aided magnetic resonance image analysis and an age-normed battery of neuropsychological tests to measure brain atrophy and cognitive function in 14 older abstinent alcoholic men and 11 older controls in the expectation that these subject groups would show the greatest and most persistent cerebral effects consequent to chronic alcoholism. The abstinent alcoholics exhibited cognitive impairments (primarily in memory and visual-spatial-motor skills) compared with the controls. In contrast, we found no difference in global cerebral atrophy between the groups, although two alcoholics had extensive atrophy compared with all other subjects. However, there was a stronger association between age and ventricular dilation in the alcoholic sample compared with controls. We conclude that a substrate other than magnetic resonance imaging-detectable global atrophy must underlie the persistent cognitive impairments evident in the sampled alcoholics. Furthermore, if there are global atrophic changes in the brain associated with chronic alcoholism, these effects are not ubiquitous and/or may be reversible in most patients with sufficient abstinence.

Aged↗
PubMed1995

H-1 MR spectroscopic imaging of white matter signal hyperintensities: Alzheimer disease and ischemic vascular dementia.

PURPOSE: To investigate the association of white matter signal hyperintensities (WMSHs) with changes in hydrogen-1 metabolites. MATERIALS AND METHODS: T2-weighted magnetic resonance (MR) imaging and H-1 MR spectroscopic imaging were performed in 21 elderly control subjects without or with minimal WMSHs, eight elderly subjects with substantial WMSHs, 11 probable Alzheimer disease patients with WMSHs, and eight ischemic vascular dementia (IVD) patients with WMSHs. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and creatine-containing metabolites (Cr) were analyzed. RESULTS: Differences in regional metabolite levels were found within the supraventricular brain of elderly control subjects. In Alzheimer disease patients, extensive WMSHs showed a lower percentage of NAA and a higher percentage of Cho compared with contralateral normal-appearing white matter (NAWM); in IVD patients, extensive and large WMSHs were associated with a higher percentage of Cho and a lower percentage of Cr compared with contralateral NAWM. CONCLUSION: Regional metabolite variation and the presence of WMSHs are important covariants that must be accounted for in analysis of MR spectroscopic data.

Aged↗
PubMed1995

Phosphorus magnetic resonance spectroscopy of human masseter muscle.

Masseter muscle metabolism is poorly understood. 31P Magnetic Resonance Spectroscopy (MRS) provides an opportunity for non-invasive study of muscle metabolism during rest, exercise, and recovery. The aim of this study was to investigate the changes in high-energy phosphates and pH in human masseter muscle associated with exertional pain. Phosphates and pH were measured with 31P Magnetic Resonance at 2.0 Tesla. The bite force was simultaneously measured with a force transducer. Continuous biting at maximum voluntary bite force (MVBF) and two intermittent biting exercises with different duty cycles were performed to pain intolerance. The light intermittent exercise did not produce pain. Brief MVBF requested at the beginning, during, and end of each exercise showed no decay. Qualitatively, changes in phosphates were similar to those reported from comparable limb muscle exercises: increased inorganic phosphate (Pi), decreased phosphocreatine (PCr), and no changes in ATP level. Quantitatively, however, the Pi/PCr ratio did not reach the levels reported in limb muscles during similar exercises. Also, the pH changed very little. Thus, the lack of fatigue was no surprise, since the level of changes in Pi/PCr and pH, reported to be associated with fatigue in limb muscles, was far less in the masseter. Pain development toward the end of the heavy exercises prevented further depletion of metabolites. Thus, the lack of fatigue generally postulated for the masseter muscle may not be due to resistance to fatigue of these fibers, but rather to the presence of pain preventing the fatigue. However, no specific metabolic changes associated with exertional pain were found.

Adenosine Triphosphate↗
PubMed1994

31phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia.

In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was performed on 20 chronic schizophrenic patients and 16 normal controls to determine if there were specific changes in high energy phosphorus and phospholipid metabolism in the frontal lobes of schizophrenic patients. Phosphorous metabolites were assessed in each of the left and right frontal as well as the left and right parietal lobes. Frontal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right frontal regions compared to controls. There was also lower left frontal inorganic phosphate (Pi) in the schizophrenic group. No group differences were noted in the left or right parietal regions. In addition, right frontal PDE and right frontal PCr were highly correlated with the hostility-suspiciousness and anxiety-depression subscales of the BPRS. This study provides further support for altered frontal lobe phosphorous metabolism in schizophrenia.

Adult↗
PubMed1994

Magnetic resonance spectroscopy of N-acetylaspartate in hypoxic-ischemic encephalopathy.

Magnetic resonance imaging and water-suppressed proton magnetic resonance spectroscopic imaging were used to study N-acetylaspartate and other metabolites in a patient with severe hypoxic-ischemic encephalopathy. The N-acetylaspartate signal, a putative marker of neuronal density, was markedly reduced in the forebrain. The relative signal intensity of choline-containing metabolites, which are more abundant in astrocytes than neurons, was increased. These results support the hypothesis that water-suppressed proton magnetic resonance spectroscopic imaging measurements of N-acetylaspartate may be useful for noninvasive detection of selective neuronal loss in a variety of disease states in the human brain.

Adolescent↗
PubMed1994

Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging.

We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolites, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate-choline ratio) and creatine-containing metabolites (N-acetylaspartate-creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline-N-acetylaspartate ratios with the N-acetylaspartate-creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.

Aged↗
PubMed1994

Automated processing for proton spectroscopic imaging using water reference deconvolution.

Automated formation of MR spectroscopic images (MRSI) is necessary before routine application of these methods is possible for in vivo studies; however, this task is complicated by the presence of spatially dependent instrumental distortions and the complex nature of the MR spectrum. A data processing method is presented for completely automated formation of in vivo proton spectroscopic images, and applied for analysis of human brain metabolites. This procedure uses the water reference deconvolution method (G. A. Morris, J. Magn. Reson. 80, 547(1988)) to correct for line shape distortions caused by instrumental and sample characteristics, followed by parametric spectral analysis. Results for automated image formation were found to compare favorably with operator dependent spectral integration methods. While the water reference deconvolution processing was found to provide good correction of spatially dependent resonance frequency shifts, it was found to be susceptible to errors for correction of line shape distortions. These occur due to differences between the water reference and the metabolite distributions.

Artifacts↗
PubMed1994

What might be the impact on neurology of the analysis of brain metabolism by in vivo magnetic resonance spectroscopy?

In vivo nuclear magnetic resonance spectroscopy (MRS) of the human brain is a recently developed technique which allows to assay noninvasively in vivo key molecules of brain metabolism. After a review of the origin of the signals detected by phosphorus and proton MRS of human brain, the impact of MRS on clinical neurology is examined. MRS of the brain does not purport to be a metabolic "biopsy", but unique applications for brain MRS are (1) quantitating the oxidative state of the brain and defining neuronal death, (2) assessing and mapping neuron damage, (3) evaluating membrane alterations, and (4) characterizing encephalopathies. In the near future brain MRS will be performed routinely after conventional MRI, as a valuable metabolic (and functional) complement to the anatomical evaluation of cerebral pathologies, particularly the toxic, metabolic and infectious encephalopathies.

Brain↗
PubMed1994

N-acetylaspartate reductions measured by 1H MRSI in cognitively impaired HIV-seropositive individuals.

We used magnetic resonance imaging (MRI) and water-suppressed proton MR spectroscopic imaging (1H MRSI) to study the effects of human immunodeficiency virus (HIV) infection on the brain. Our recent in vivo finding of lower N-acetylaspartate (NAA), a putative marker of neurons, in the supraventricular brain of cognitively impaired HIV-seropositive patients (CISP) compared to noninfected controls was replicated in a new cohort of 13 CISP patients and extended to include 10 high-risk homosexual HIV-seronegative controls. Throughout the supraventricular brain the ratio of NAA to choline-containing metabolites (NAA/Cho) was lower in CISP subjects than in high-risk controls (1.98 +/- 0.36 vs. 2.35 +/- 0.29, p = 0.016), and the ratio of NAA to creatine-containing metabolites (NAA/Cr) was also lower in CISP subjects than in high-risk controls (3.02 +/- 0.44 vs. 3.56 +/- 0.39, p = 0.007) with Cho/Cr unchanged in both groups. These findings indicate a NAA reduction which suggests neuron loss and/or dendritic and axonal damage. Homosexual high-risk HIV-seronegative controls had metabolite measures similar to previously studied heterosexual HIV-seronegative controls. NAA measures in six cognitively normal HIV-seropositive subjects (CNSP) (NAA/Cho = 2.34 +/- 0.39, NAA/Cr = 3.42 +/- 0.69) were similar to those of controls and tended to be increased relative to those in cognitively impaired HIV-seropositive subjects. This study demonstrates that reduced NAA in the supraventricular brain is associated with the development of severe cognitive impairments secondary to HIV infection and that 1H MRSI methodology reliably detects HIV effects on the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging.

We used magnetic resonance imaging (MRI) and water-suppressed proton magnetic resonance spectroscopic imaging to study the effects of human immunodeficiency virus (HIV) infection on the brains of 10 individuals with cognitive impairment due to HIV and seven normal controls. 1H spectra from nine 2.5-ml volumes in the centrum semiovale and the mesial cortex showed significantly reduced N-acetylaspartate (NAA) relative to choline and creatine in the cognitively impaired HIV-infected subjects. This reduction was due to a nonlocalized decrease of NAA in these patients, only two of whom had moderate atrophy and white matter signal hyperintensities on MRI. Since NAA is a putative neuronal marker, the findings suggest neuronal damage in early stages of HIV infection that is not evident on standard MRI and are consistent with the neuropathologically known neuronal loss.

Adult↗
PubMed1992

Metabolic response of the human heart to inotropic stimulation: in vivo phosphorus-31 studies of normal and cardiomyopathic myocardium.

In order to determine if an increase in myocardial oxygen consumption is accompanied by changes in high energy phosphates in normal subjects and patients with dilated cardiomyopathy, phosphorus-31 spectra were acquired under resting conditions and during dobutamine infusion. In seven normal subjects, dobutamine raised the rate-pressure product to 226% of control. The ratio of PCr/ATP was 1.86 +/- 0.17 (mean +/- SE) under resting conditions and 1.90 +/- 0.22 (P = 0.44) with dobutamine infusion. In eight patients with dilated cardiomyopathy, dobutamine raised the rate-pressure product to 161% of control. As in the normal subjects, the ratio of PCr/ATP under resting conditions (1.63 +/- 0.24) was unchanged during dobutamine infusion (1.57 +/- 0.24, P = 0.38). These data indicate that increases in cardiac work do not have a major effect on high energy phosphate concentrations in normal subjects or in patients with clinically compensated dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1992

Phosphorus-31 magnetic resonance metabolite imaging in the human body.

This work examines the feasibility of three-dimensional phosphorus-31 magnetic resonance spectroscopic imaging (31P MRSI) of metabolites in the human body using nonselective excitation with a single large circular surface coil for transmitting and receiving. The potential and limitations of this approach to clinical imaging are demonstrated on four selected examples: normal liver and heart, hematoma in the calf, and lymphoma in the groin. The obtained metabolite images showed anatomical detail and allowed differentiation of body organs and pathologic tissue from adjacent tissue. Three-dimensionally localized 31P spectra were reconstructed from nominal volumes of 4 to 15 cm3. These spectra showed characteristic resonances and metabolite intensity ratios for the tissue of origin demonstrating good three-dimensional localization. We conclude that surface coil 31P MRSI of body organs to map metabolite distributions is practically feasible with this approach, but due to experimental limitations, clinical utility requires technical improvements.

Heart↗
PubMed1992

Hepatic cancers and their response to chemoembolization therapy. Quantitative image-guided 31P magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Hepatic embolization combined with intra-arterial administration of cytostatic drugs (chemoembolization) is frequently used to treat primary and metastatic cancers to the liver. Quantitative phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to assess the metabolic state of hepatic cancers and their metabolic response to chemoembolization. METHODS: Fifteen localized 31P MRS studies were performed on five patients with liver tumors. Thirteen healthy volunteers served as controls. Metabolite ratios and molar metabolite concentrations were calculated. RESULTS: Untreated hepatic tumors, relative to normal controls, showed elevated phosphomonoester/adenosine triphosphate (PME/ATP) ratios, reduced concentrations of ATP and inorganic phosphate (Pi), and normal phosphodiester (PDE) concentrations. As an acute response to chemoembolization, ATP, PME, and/or PDE concentrations diminished, whereas Pi concentrations increased or stayed relatively constant. Long-term follow-up after chemoembolization showed decreased PME/ATP and increased ATP concentrations in the absence of changes on standard magnetic resonance and computed tomographic images. CONCLUSIONS: These preliminary spectroscopic data suggest that quantitative 31P MRS can be successfully used to monitor directly metabolic response to hepatic chemoembolization.

Adenocarcinoma↗
PubMed1992

Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging.

Areas of high signal intensity in white matter are identified on brain magnetic resonance (MR) imaging studies in 25%-50% of elderly subjects. The authors used phosphorus-31 MR spectroscopy to characterize the metabolic status of hemispheric white matter brain volumes in 30 elderly subjects with white matter areas of high signal intensity at MR imaging. Compared with white matter volumes with no or minimal areas of high intensity, white matter volumes with extensive areas of high intensity evidenced a 26% decrease in the adenosine triphosphate (ATP)/inorganic phosphate (Pi) ratio (P = .03) and a 21% decrease in the ATP concentration (P = .05), with the Pi level unchanged. A pilot P-31 spectroscopic imaging study in a subject with a large, coalescing white matter area of high signal intensity demonstrated large reductions in metabolite concentrations in the high-signal-intensity area. These results suggest that extensive white matter areas of high signal intensity indicate a process that affects white matter cellular energy metabolism.

Adenosine Triphosphate↗