A 31phosphorous magnetic resonance spectroscopy study of diazepam does not affect brain phosphorous metabolism.
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Adenosine Triphosphate↗
Biomedical subjects
M W Weiner
Publications and source records attributed to M W Weiner.
31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia.
Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.
Adenosine Triphosphate↗
Selective depletion of tumor ATP by 2-deoxyglucose and insulin, detected by 31P magnetic resonance spectroscopy.
The purpose of this study was to investigate whether substrate deprivation acutely and selectively decreases ATP concentration in an experimental sarcoma. Two methods of substrate deprivation were examined: glycolysis was inhibited using 2-deoxyglucose (2DG), and plasma substrate levels were reduced using insulin. The effects of treatment on tumor ATP, inorganic phosphate, and pH were studied by 31P nuclear magnetic resonance spectroscopy. 2DG (2 g/kg) was administered i.p. to rats bearing s.c. methylcholanthrene-induced sarcomas. Inhibition of glycolysis by 2DG caused a 52 +/- 13% (SE) decrease in the tumor ATP to inorganic phosphate ratio, associated with a decrease in pH of 0.38 +/- 0.10 unit. The same dose of 2DG caused no significant change in the ratio of phosphocreatine to ATP in brain. Insulin (125 units/kg, i.p.) caused a 68% decline in plasma glucose and a 71% decline in betahydroxybutyrate compared to saline-treated animals. Concomitantly, 31P nuclear magnetic resonance spectroscopy detected a 48 +/- 13% decrease in sarcoma ATP, with a reciprocal elevation of inorganic phosphate in insulin-treated animals. In contrast, the brain phosphocratine/ATP ratio was unaffected by insulin. These results suggest that large tumors are acutely sensitive to inhibition of glycolysis and reductions in plasma levels of substrates for oxidative phosphorylation and glycolysis, while the brain is unaffected. In addition, this work provides support for the use of 31P nuclear magnetic resonance spectroscopy to monitor tumor response to therapy.
Adenosine Triphosphate↗
1H spectroscopic imaging of rat brain at 7 tesla.
1H magnetic resonance spectroscopic imaging has been used to obtain metabolite maps of the rat brain. The spin-echo-based technique has been evaluated with respect to water and lipid suppression and sensitivity. Metabolite maps were constructed for choline, creatine + phosphocreatine, amino acids, N-acetyl aspartate, and lactate. A spatial resolution of 3 x 3 mm (in plane) with 7-mm-thick slices was achieved routinely in 60-min (16 x 16 phase encodings) acquisitions. For higher intensity resonances, metabolite maps could be constructed in as little as 10 min. Results from phantoms and from rats under normal and focal ischemia conditions are presented.
Amino Acids↗
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↗
Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities.
A modified ISIS method, for image-selected localized proton magnetic resonance spectroscopy (1H MRS), was used to determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities (WMSH). First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly (P less than 0.05) increased from 0.23 +/- 0.02 (mean +/- SE), 0.20 +/- 0.01, and 0.05 +/- 0.01, respectively in the normal group to 0.39 +/- 0.08, 0.37 +/- 0.05, and 0.48 +/- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +/- 0.02 in the normal group to 0.64 +/- 0.05 in the WMSH group. Third, in normal white matter, the concentration of N-acetyl aspartate, choline, and lactate was estimated to 11.5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM.
Aged↗
Three-dimensional 1H spectroscopic imaging of cerebral metabolites in the rat using surface coils.
Three dimensional metabolite maps of protonated metabolites were obtained using 1H magnetic resonance spectroscopic imaging at 7 T. Surface coils were used to increase sensitivity and spatial resolution significantly over a volume coil two-dimensional acquisition. Adiabatic pulses were employed to provide homogeneous B1 excitation and frequency selective refocusing over the volume of the rat brain. These techniques were employed to obtain three-dimensional spectroscopic imaging spectra from nominal voxel volumes of 9-30 microliters from rat brain. The improved spatial resolution and sensitivity are also demonstrated with studies of focal ischemia in the rat.
Animals↗
Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.
The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.
Adult↗
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↗
3D phase encoding 1H spectroscopic imaging of human brain.
A three-dimensional (3D) phase-encoding proton spectroscopic imaging method is presented for a whole body MRI/MRS system. Metabolite images at 2 T of choline, creatine, and N-acetyl aspartate (NAA) of normal brain were obtained with a spatial resolution of 1.5 cc. With PRESS volume preselection and outer volume suppression pulses, brain regions close to the skull could be studied without significant contamination by lipid and water signals.
Brain↗
Spectroscopic imaging display and analysis.
A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain.
Humans↗
Elevated lactate and alkalosis in chronic human brain infarction observed by 1H and 31P MR spectroscopic imaging.
The goal of this study was to investigate lactate and pH distributions in subacutely and chronically infarcted human brains. Magnetic resonance spectroscopic imaging (MRSI) was used to map spatial distributions of 1H and 31P metabolites in 11 nonhemorrhagic subacute to chronic cerebral infarction patients and 11 controls. All six infarcts containing lactate were alkalotic (pHi = 7.20 +/- 0.04 vs. 7.05 +/- 0.01 contralateral, p less than 0.01). This finding of elevated lactate and alkalosis in chronic infarctions does not support the presence of chronic ischemia; however, it is consistent with the presence of phagocytic cells, gliosis, altered buffering mechanisms, and/or luxury perfusion. Total 1H and 31P metabolites were markedly reduced (about 50% on average) in subacute and chronic brain infarctions (p less than 0.01), and N-acetyl aspartate (NAA) was reduced more (approximately 75%) than other metabolites (p less than 0.01). Because NAA is localized in neurons, selective NAA reduction is consistent with pathological findings of a greater loss of neurons than glial cells in chronic infarctions.
Adult↗
Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy.
Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.
Adenosine Diphosphate↗
Effect of supranormal coronary blood flow on energy metabolism and systolic function of porcine left ventricle.
OBJECTIVE: The goal was to determine if supranormal coronary blood flow increases myocardial oxygen consumption, high energy phosphate levels, and systolic function in the in situ autoperfused heart. METHODS: Thirteen anaesthetised open chest pigs with an intact, autoperfused coronary circulation, weight 30-40 kg, were studied. Measurements were made under basal conditions and during regional hyperperfusion of the anterior left ventricle produced by intracoronary infusion of adenosine (mean dose 3.3 mumol.min-1). Doppler coronary blood flow velocity in the anterior descending coronary artery, arterial and anterior interventricular venous blood oxygen content, high energy phosphates (by transmurally localised 31P NMR), and myocardial wall thickening (by sonomicrometry) were measured. RESULTS: With adenosine, coronary flow was increased to 355(SEM 59)% of control. Supranormal coronary flow produced no significant changes in anterior left ventricular oxygen consumption [99(12)% of control]. 31P NMR spectroscopy revealed no significant changes in the peak intensities of phosphocreatine or ATP in either the subendocardium or subepicardium (90-97% of control). Systolic anterior left ventricular wall thickening also did not change [107(13)% of control]. CONCLUSIONS: Supranormal coronary flow does not augment myocardial oxygen consumption, high energy phosphates, or systolic function in the in situ autoperfused heart. Myocardial oxygen delivery does not limit oxidative metabolism under normal conditions.
Adenosine↗
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↗
Decreased phosphorus metabolite concentrations and alkalosis in chronic cerebral infarction.
A study was performed to determine quantitatively the alterations in phosphorus metabolite concentrations and pH in regions of the human brain damaged by chronic stroke. Image-guided phosphorus-31 magnetic resonance spectroscopy was performed on the brains of eight healthy subjects and six patients with cerebral infarction of more than 3 months duration. Phosphorus metabolite concentrations in infarcted regions were reduced 8%-67%. Significant decreases occurred in phosphomonoester (PME), phosphodiester (PDE), and adenosine triphosphate (ATP) concentrations, while inorganic phosphate (Pi) and phosphocreatine (PCr) concentrations showed smaller, nonsignificant decreases. The PCr/ATP ratio was significantly increased, while the ATP/Pi ratio was somewhat lower. The phospholipid ratio PDE/PME was also significantly increased, while the ratios of phospholipid (PME, PDE) to phosphate (PCR, Pi) metabolites were significantly decreased. The pH of the infarcted region indicated significantly more alkalinity than in the normal brain. The results suggest that chronic stroke is associated with significant changes in brain metabolite concentrations and pH that are different from those reported for other brain diseases.
Adenosine Triphosphate↗
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↗
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.
Adult↗