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Biomedical subjects

J R Alger

Publications and source records attributed to J R Alger.

At least 55 records · Page 3Linked to original sources
PubMed1993

Histopathologic correlates of abnormal water diffusion in cerebral ischemia: diffusion-weighted MR imaging and light and electron microscopic study.

PURPOSE: To correlate the findings on diffusion-weighted magnetic resonance (MR) images with the cytologic and histologic findings in ischemic tissue. MATERIALS AND METHODS: A photochemical model of cerebral infarction in rats was studied with diffusion- and T2-weighted MR imaging. The development of lesions was followed from 20 minutes to 5 days after the onset of ischemia. Apparent water diffusion coefficient (ADC) maps were calculated and correlated with light and electron microscopic findings. RESULTS: T2-weighted images clearly showed vasogenic edema but did not enable distinction between areas with cellular damage and the surrounding edematous regions. In contrast, the ADC, which was elevated in nonischemic edematous regions, was diminished in areas with histologic evidence of ischemic damage or necrosis. In the core of the infarct, the ADC became elevated when electron microscopy revealed cellular lysis. CONCLUSION: Diffusion-weighted images may help ascertain the extent of cellular damage and death after stroke.

Animals↗
PubMed1992

Cerebral lactate turnover after electroshock: in vivo measurements by 1H/13C magnetic resonance spectroscopy.

We reported earlier that brain activation by 10 s of cortical electroshock caused prolonged elevation of brain lactate without significant change in intracellular pH, brain high-energy phosphorylated metabolites, or blood gases. The metabolic state of the elevated lactate has been investigated in further experiments using combined, in vivo 1H-observed 13C-edited nuclear magnetic resonance spectroscopy (NMRS), homonuclear J-edited 1H-NMRS, and high-resolution 1H-NMRS of perchloric acid extracts to monitor concentrations and 13C-isotopic fractions of brain and blood lactate and glucose. We now report that electroshock-elevated lactate pool in rabbit brain approaches equilibrium with blood glucose within 1 h. There was nearly complete turnover of the raised lactate pool in brain; any pool of metabolically inactive lactate could not have been > 5% of the total. In the same experiments, blood lactate underwent < 50% turnover in 1 h. The new 1H-spectroscopic methods used for these experiments are readily adaptable for the study of human brain and may be useful in characterizing the metabolic state of elevated lactate pools associated with epilepsy, stroke, trauma, tumors, and other pathological conditions.

Animals↗
PubMed1992

The utilization of magnetic resonance imaging in physiology.

The literature that we have surveyed suggests that MRI will follow the somewhat unusual path from a routine clinical tool to a valuable instrument in physiological research. Its ability to provide both anatomic and limited functional information makes it possible for the physiologist to develop a detailed understanding of an intact mammalian system.

Animals↗
PubMed1992

Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance.

Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy.

Adolescent↗
PubMed1991

A pitfall associated with lactate detection using stimulated-echo proton spectroscopy.

At TE values of 136 ms, it has recently been shown that the lactate methyl signal, when obtained with a stimulated-echo (STE) sequence, is modulated at the zero-quantum (ZQ) frequency when TM is varied. Here we describe an additional modulation of the ZQ lactate signal, due to spin-spin coupling, that results in a 10-fold reduction in the lactate signal for TM intervals ranging between 48 and 84 ms (and at multiples of 136 ms thereof). Because of this J-modulation, improper choice of TE and TM intervals may give false negative results for lactate detection by STE spectroscopy.

Alanine↗
PubMed1990

Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths.

The authors measured in vivo signal intensity on magnetic resonance (MR) images and postmortem iron concentrations in the brains of three young and two old rhesus monkeys. T2-weighted MR imaging was done at 0.5, 1.5, 2.0, and 4.7 T. Relative assessment of iron concentration was made from the optical density of brain sections stained with the Perls' method intensified with diaminobenzidine. MR imaging and optical density measurements were made in the centrum semiovale (white matter) and in four gray matter areas: the insular cortex, caudate nucleus, putamen, and globus pallidus, the latter three of which accumulate significant iron deposits with age. High optical density and decreased signal intensity were found in these areas, and the inverse correlation between gray matter/white matter signal ratio and optical density was in good agreement with the theory of T2 shortening caused by diffusion of water through magnetic inhomogeneities. However, the dependence of T2 shortening on field strength was not quadratic, as expected for paramagnetic iron, but instead showed a marked leveling off at higher field strengths. This magnetic "saturation" is explainable by antiferromagnetism and superparamagnetism of the ferritin core and has been observed in ferritin solutions at low temperatures. Similar observations at body temperature are needed before the iron-ferritin explanation for T2 shortening can be considered proved.

Aging↗
PubMed1990

Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET.

Localized hydrogen-1 magnetic resonance (MR) spectroscopy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were employed to obtain metabolic information from intracranial gliomas. Advantages and difficulties associated with comparison of results from the two modalities were realized. Forty patients were studied with H-1 MR spectroscopy. MR signal intensities from lactate, N-acetylaspartate (NAA), choline, and creatine from a volume of interest containing the tumor and a contralateral volume were obtained and evaluated. NAA signal intensities were generally decreased in the tumor spectra, and choline signal intensities were elevated. H-1 MR spectroscopy was unsuccessful in eight patients, and FDG PET scans were not obtained in four of the patients with successful MR spectroscopic examinations. Lactate signal intensity was detected in 10 of the 28 patients who had successful H-1 MR spectroscopic and FDG PET studies. Lactate signal intensities were observed in lesions shown at FDG PET to be hypermetabolic, as well as in lesions found to be hypometabolic.

Adult↗
PubMed1990

Cerebral blood flow in experimental ischemia assessed by 19F magnetic resonance spectroscopy in cats.

We evaluated a 19F magnetic resonance spectroscopic technique that detects Freon-23 washout as a means of measuring cerebral blood flow in halothane-anesthetized adult cats during and after transient cerebral ischemia produced by vascular occlusion. The experiments were performed to test the ability of this recently developed method to detect postischemic flow deficits. Results were consistent with postischemic hypoperfusion. The method also proved valuable for measuring small residual flow during vascular occlusion. Our experiments indicate that this method provides simple, rapid, and repeatable flow measurements that can augment magnetic resonance examinations of cerebral metabolic parameters in the study of ischemia.

Animals↗
PubMed1989

High field localized proton spectroscopy in small volumes: greatly improved localization and shimming using shielded strong gradients.

The availability of shielded gradients facilitates accurate single-voxel spectroscopy. Exact localization (90-99%) of volumes as small as 2 x 2 x 2 mm is demonstrated using a modified stimulated echo sequence. Strong gradient pulses (up to 200 mT/m) are employed to clear the stimulated echo of unwanted magnetization, enabling superior (single-scan) shimming of the selected volume. In vivo and in vitro proton NMR results at 4.7 T are presented.

Animals↗
PubMed1989

Evaluation of a newly discovered water suppression pulse sequence for high-field in vivo 1H surface coil NMR spectroscopy.

The use of a water-suppressing spin-echo pulse sequence reported recently (V. Sklenar and A. Bax, J. Magn. Reson. 74, 469 (1987); M. von Kienlin, M. DeCorps, J. P. Albrand, M. F. Foray, and P. Blondet, J. Magn. Reson. 76, 169 (1987)) was evaluated for in vivo brain proton surface coil NMR spectroscopy. The studies were performed on cat brain using surface coils at 4.7 T. The sequence produced brain spectra with adequate water suppression, and a broader excitation profile than sequences which form spin echoes using 1331 pulses (P. J. Hore, J. Magn. Reson. 54, 539 (1983); H. P. Hetherington, M. J. Avison, and R. G. Shulman, Proc. Natl. Acad. Sci. USA 82, 3115 (1985)). The phase artifacts were smaller than those produced in 1331 methods, but theoretical analysis showed they should not be completely absent. The effectiveness of lengthening the spin-echo delay in the new sequence for suppression of unwanted lipid resonances was demonstrated. The sequence was shown to be capable of detecting lactate formation and clearance in a global cerebral ischemia experiment.

Animals↗
PubMed1989

On the origin of paramagnetic inhomogeneity effects in blood.

Hydrogen, sodium, and fluorine (added F-) NMR spectra of venous and oxygenated blood were measured. The fluorine resonance was seen as a single peak in both samples, and all three resonances exhibited the same deoxy-oxy shift. Because F- exchanges slowly across the red cell membrane, and because sodium is 95% extracellular, these results suggest that the intra-extracellular field difference delta B is less than 0.1 ppm. A small value of delta B tends to rule out transmembrane exchange as an important contributor to relaxation in MRI of blood and hematomas. However, the broadening of the resonances with deoxygenation, by 0.3-0.4 ppm, indicates that both intra- and extracellular gradients are of comparable and sufficient magnitude to produce the T2-weighted hypointensity seen in clinical magnetic resonance images of hematomas at high fields.

Blood↗
PubMed1989

Phase-distortion-free in vivo surface coil proton spectroscopy.

A 1-11 water suppression pulse sequence for phase-distortion-free surface coil NMR spectroscopy was constructed and tested in vivo on cat brain. The sequence produces brain spectra free of phase distortions, but some degradation of water suppression quality compared to closely related sequences which produce phase distortions was observed.

Animals↗
PubMed1989

Assessment of postischemic cerebral energy metabolism in cat by 31P NMR: the cumulative effects of secondary hypoxia and ischemia.

The sensitivity of cerebral energy metabolism to ischemic and hypoxic stresses following global cerebral ischemia was evaluated in a cat model using 31P nuclear magnetic resonance (NMR) spectroscopic methods. Complete global cerebral ischemia of 5 to 10 min in length was produced at 1 h intervals by reversible arterial occlusion, permitting continuous monitoring of NMR and EEG. Ischemia appeared to produce slightly more severe energy failure in animals that had previously experienced an ischemic injury. Preischemic hypoxia (5% O2 for 5 min) resulted in minor changes in the levels of phosphocreatine and intracellular inorganic phosphate, which were slightly amplified in animals that previously experienced ischemia.

Animals↗
PubMed1989

High-field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy.

We analyzed specimens of histologically normal human cerebrum obtained at surgery for medically refractory epilepsy using proton magnetic resonance spectroscopy. Perchloric acid extracts of anterolateral temporal lobe cortex contained greater concentrations of creatine, N-acetylaspartate, gamma-aminobutyric acid, alanine, and glutamate than the under lying white matter, which contained more acetate. Frontal and temporal lobe specimens composed of both gray and white matter failed to show statistically significant differences in the concentrations of creatine, N-acetylaspartate, alanine, aspartate gamma-aminobutyric acid, glutamate, glycine, taurine, threonine, valine, acetate, choline, beta-hydroxybutyric acid, inositols, lactate pyruvate, or succinate.

Adult↗
PubMed1988

High-resolution proton magnetic resonance spectroscopy of rabbit brain: regional metabolite levels and postmortem changes.

The changes in 16 cerebral metabolites produced by cardiac arrest and subsequent room temperature autolysis were studied using high-resolution proton nuclear magnetic resonance spectroscopy. Biopsies of rabbit cerebral cortex, cerebral white matter, and cerebellum were quantitatively analyzed for acetate, alanine, gamma-aminobutyric acid, creatine, glutamate, glycine, inositol, lactate, N-acetylaspartate, phosphocreatine, succinate, taurine, and threonine. Of these, N-acetylaspartate and the total creatine pool are the best candidates for use as concentration reference standards linking in vitro to in vivo 1H nuclear magnetic resonance measurements. Both changed little immediately after death, and they varied in a distinctive way among cortex, white matter, and cerebellum.

3-Hydroxybutyric Acid↗
PubMed1987

31P NMR saturation-transfer and 13C NMR kinetic studies of glycolytic regulation during anaerobic and aerobic glycolysis.

31P NMR saturation-transfer techniques have been employed in glucose-grown derepressed yeast to determine unidirectional fluxes in the upper part of the Embden-Meyerhof-Parnas pathway. The experiments were performed during anaerobic and aerobic glycolysis by saturating the ATP gamma resonances and monitoring changes in the phosphomonoester signals from glucose 6-phosphate and fructose 1,6-bis-phosphate. These experiments were supplemented with 13C NMR measurements of glucose utilization rates and 13C NMR label distribution studies. Combined with data obtained previously from radioisotope measurements, these 31P and 13C NMR kinetic studies allowed estimation of the net glycolytic flow in addition to relative flows through phosphofructokinase (PFK) and Fru-1,6-P2ase during anaerobic and aerobic glycolysis. The 31P NMR saturation-transfer results are consistent with previous results obtained from measurements of metabolite levels, radioisotope data, and 13C NMR studies [den Hollander, J.A., Ugurbil, K., Brown, T.R., Bednar, M., Redfield, C., & Shulman, R.G. (1986a) Biochemistry 25, 203-211], providing additional support for in vivo measurement of the flows during glycolysis.

Aerobiosis↗
PubMed1987

31P magnetization transfer studies of creatine kinase kinetics in living rabbit brain.

The kinetics of the CK reaction in the living rabbit brain was studied by three 31P magnetization transfer methods: inversion recovery (IR), inversion transfer (IT), and steady-state saturation transfer (SSST). Longitudinal relaxation rates (tau -1) were determined from IR and IT experiments. The values were 0.88 +/- 0.08 s-1 for PCr and 2.45 +/- 0.39 s-1 for gamma-ATP. Analysis of the results of SSST experiments in which gamma-ATP was saturated yielded a forward rate constant kF of 0.53 +/- 0.07 s-1. Upon saturation of PCr no change in the gamma-ATP signal could be detected in SSST. An average reverse rate constant (kR +/- S.D.) of 0.52 +/- 0.04 s-1 was estimated by analyzing IT data from three experiments with selective inversion of gamma-ATP. The standard error of kR was 50%. The average [PCr]/[ATP] of 1.21 +/- 0.16 together with the values of kF and kR yielded a forward-to-reverse flux ratio of 1.23. Within our limits of accuracy this ratio was not significantly different from 1.0, thus suggesting that in the brain the forward and reverse CK fluxes are equal.

Adenosine Triphosphate↗