Intracellular pH measured by NMR: methods and results.
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Animals↗
Biomedical subjects
J R Alger
Publications and source records attributed to J R Alger.
31P NMR of alkaline phosphatase. Saturation transfer and metal-phosphorus coupling.
The rate constants which characterize the formation and breakdown of the noncovalent (E.P) and covalent (E-P) enzyme-phosphate intermediates on the alkaline phosphatase reaction pathway are known to be sensitive to the nature of the metal ion bound to the enzyme. 31P NMR saturation transfer has been demonstrated to provide a simple and sensitive method for measuring the metal ion dependence of these rates under equilibrium conditions. When the native Zn2+ was replaced by Cd2+, the 31P NMR spectrum at high pH revealed a new resonance at 12.6 ppm which has been assigned to the noncovalent enzyme.phosphate complex. Reconstituting the enzyme with enriched 113Cd2+ caused this unusually downfield-shifted resonance to appear as a doublet due to 113Cd-31P spin coupling (2J31P-O-113Cd = 30 Hz). This result provides the first unequivocal evidence for direct metal-phosphate interaction in alkaline phosphatase.
Alkaline Phosphatase↗
Nuclear magnetic resonance study of acetic acid permeation of large unilamellar vesicle membranes.
The permeation of acetic acid through large unilamellar phospholipid vesicle membranes has been investigated using the unique capability of nuclear magnetic resonance to characterize flow under pseudo-equilibrium conditions. Two types of experiments have been employed: total line shape analysis and selective population transfer. These techniques are sensitive to permeation on time scales ranging form 0.001 to 10.0 s. The permeation rate dependence on pH and acetic acid concentration indicates that the neutral acetic acid monomer is the dominant permeant species with a permeation coefficient of 5 +/- 2 x 10-4 cm/s. Mechanisms of permeation and the applicability of nuclear magnetic resonance methodology are discussed.
Acetates↗
Absolute quantitation of short TE brain 1H-MR spectra and spectroscopic imaging data.
A method for determining the concentrations of the materials that produce the well-resolved singlet signals in short TE brain 1H MR spectroscopic examinations is presented. Concentration determination is achieved by a water-referencing procedure. The ratios of the areas of the choline, total creatine, and N-acetyl signals to that of the water signal from the same volume of interest (VOI) are determined using acquisitions with and without water suppression. The tissue concentrations of the molecules producing the three signals can then be determined if the water concentration in the VOI can be found. This is done with a density-weighted MR study. The MR study provides the ratio of the mean MR signal amplitude from the VOI to that from an external standard containing a known water concentration. The method's flexibility is illustrated by using it with two different single-volume localization schemes and spectroscopic imaging. Preliminary evaluations of accuracy and reproducibility are made in phantom, animal, and limited human studies. The method's advantages and limitations are discussed.
Acetylation↗
Transsynaptic reduction in N-acetyl-aspartate in cerebellar diaschisis: a proton MR spectroscopic imaging study.
OBJECTIVE: To determine if the transneuronal cerebellar hemispheric metabolic asymmetry seen in crossed cerebellar diaschisis, and readily detected with positron emission tomography (PET), is associated with alterations in metabolite signal intensities on [1H]MR spectroscopic (MRS) imaging when compared with the normal pattern and distribution of cerebellar metabolites. MATERIALS AND METHODS: The pattern and distribution of metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, creatine, phosphocreatine, and lactate] in the cerebellum, using [1H]MRS imaging, were studied in a patient with documented long-standing (3 years duration) crossed cerebellar diaschisis and seven normal subjects. Cerebellar diaschisis was detected with fluorodeoxyglucose-PET imaging. Single slice [1H]MRS imaging was carried out at 1.5 T. RESULTS: There was a marked reduction in NAA signal intensity in the diaschitic cerebellar hemisphere but minimal reduction in choline and creatine signal intensities. The decrease in NAA signal intensity was most marked in the middle cerebellar peduncle and white matter of the diaschitic cerebellar hemisphere. In the normal subjects and in the uninvolved cerebellar hemisphere of the patient the NAA signal intensity was more prominent in the white matter than the cerebellar cortex. CONCLUSION: Our data indicate (a) transneuronal metabolic effects can be detected with [1H]MRS imaging and (b) there is a differential distribution of metabolite signal intensities in the cerebellum with NAA signal intensity predominantly localized to axons of the cerebellar fiber tracts rather than neuronal cell bodies in the cortex and the converse is true for choline and creatinine signal intensities.
Adult↗
Mapping therapeutic response in a patient with malignant glioma.
Short-interval scanning of patients offers a detailed understanding of the natural progression of tumor tissue, as revealed through imaging markers such as contrast enhancement and edema, prior to therapy. Following treatment, short-interval scanning can also provide evidence of attenuation of growth rates. We present a longitudinal imaging study of a patient with glioblastoma multiforme (GBM) scanned 15 times in 104 days on a 3 T MR scanner. Images were analyzed independently by two automated algorithms capable of creating detailed maps of tumor changes as well as volumetric analysis. The algorithms, a nearest-neighbor-based tissue segmentation and a surface-modeling algorithm, tracked the patient's response to temozolomide, showing an attenuation of growth. The need for surrogate imaging end-points, of which growth rates are an example, is discussed. Further, the strengths of these algorithms, the insight gained by short-interval scanning, and the need for a better understanding of imaging markers are also described.
Algorithms↗
The 1991 Nobel Prize in chemistry awarded to an MRI investigator.
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Chemistry↗
MR of diffusion slowing in global cerebral ischemia.
PURPOSE: To investigate the causal connections between ischemia and the hyperintensity in diffusion-weighted MR images that has been associated with it. METHODS: Diffusion-weighted and T2-weighted MR imaging were used in a feline global cerebral ischemia/reperfusion model. Single 30-minute vascular occlusions followed by reperfusion were studied. Global occlusions were used to avoid interpretive complications associated with the temporally unstable hemodynamics of the penumbral zones around focal occlusions and the possible growth of the ischemic and penumbral regions with time. RESULTS: Diffusion-weighted hyperintensity and the associated diffusional slowing were not attributable exclusively to the cessation of blood flow because: 1) it does not appear abruptly at the onset of ischemia; 2) it resolves slowly early in reperfusion; and 3) it reappears after prolonged reperfusion. CONCLUSION: The times during which diffusion-weighted hyperintensity is manifested during ischemia, and recovers with reperfusion, point to a role for energy metabolism failure.
Animals↗
Reproducibility of proton MR spectroscopic imaging findings.
PURPOSE: To study the intraindividual, interindividual, and intraregional reproducibility of multisection proton MR spectroscopic imaging in healthy adults. METHODS: Six subjects were studied three times with proton MR spectroscopic imaging. Multisection long-echo-time proton MR spectroscopic imaging permits simultaneous acquisition of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm-thick sections divided into 0.84-mL single-volume elements. Regions of interest were the frontal cortex, the occipital cortex, the parietal cortex, the insular cortex, the cingulate gyrus, the centrum semiovale, the thalamus, and the caudate. Statistical evaluation was performed by analyses of variance and components of variance method. RESULTS: The ratio NAA/Cr showed the lowest overall coefficient of variation (CV, %) in most of the regions of interest (range, 8.9 to 26.1). Interregional differences in the overall CV were present. Interindividual CVs ranged from 4.2 to 8.7 for NAA/Cr, from 6.8 to 17.4 for NAA/Cho, and from 5.0 to 13.6 for Cho/Cr. Intraindividual CVs ranged from 8.2 to 22.2 for NAA/Cr, from 12.8 to 25.8 for NAA/Cho, and from 4.5 to 21.0 for Cho/Cr. Intraregional CVs ranged from 12.3 to 21.2 for NAA/Cr, from 13.0 to 20.4 for NAA/Cho, and from 12.2 to 18.9 for Cho/Cr. CONCLUSIONS: Proton MR spectroscopic imaging showed good overall reproducibility. The finding of interregional variations of CV indicates that care is needed when using this imaging technique for follow-up studies.
Adult↗