Search PubMed⌕ Search

Biomedical subjects

J W Prichard

Publications and source records attributed to J W Prichard.

At least 19 recordsLinked to original sources
PubMed1997

Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks.

Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at 100 Hz) of varying durations (0.1-10 s), with diffusion-weighted echo planar imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC) decreased after either single or repeat electroshock trains. ADC reductions were observed within 6 s after the first shock. The size of the affected area of the brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s) train, and also increased with the duration of electroshock trains. ADC reduction was reproducible in extent and time course after single 10-shock trains and was reversible. In the affected pixels the mean ADC reduction was 4% for a single shock train (0.1 s), and 7-8% for trains repeated once a minute, independent of electroshock train duration. The results indicate that neuronal activity associated with electrostimulation may be monitored with water diffusion measurements, and they may be useful for measuring the severity of seizure activity in patients with medically intractable epilepsy.

Animals↗
PubMed1997

Homocarnosine and the measurement of neuronal pH in patients with epilepsy.

Homocarnosine is a dipeptide of gamma-aminobutyric acid (GABA) and histidine found uniquely in the brain, most likely in a subclass of GABAergic neurons. By comparison of spectra from the occipital lobe of patients receiving a homocarnosine elevation drug to normal subjects we have assigned two elevated resonances in the short TE 1H MRS spectrum to homocarnosine. These resonances are partially resolved at 7.05 and 8.02 ppm in a short TE spectrum at 2.1 T when macromolecule resonances are removed by subtraction of a spectrum in which the metabolite resonances are nulled by inversion recovery. The chemical shift of both of these resonances is sensitive to pHi. By comparison with a titration curve the pHi was calculated from the downfield resonance to be 7.06 in the patient group which is similar to values reported using the P(i) resonance. Based on the in vivo results and theoretical considerations the potential sensitivity for using nonelevated homocarnosine to measure pH is similar to that of P(i) under physiological conditions.

Adult↗
PubMed1997

New nuclear magnetic resonance data in epilepsy.

Nuclear magnetic resonance methods as a whole have contributed as much to the study and treatment of epilepsy as to any branch of medicine. The pace of the progress in this field increases as recently developed nuclear magnetic resonance techniques mature into practical tools for epilepsy research and management. Recent examples of such progress include new data on seizure-related brain water diffusion changes, brain metabolic abnormalities in epileptic patients, and pharmacologic manipulation of brain gamma-aminobutyric acid.

Animals↗
PubMed1996

Effects of osmotically driven cell volume changes on diffusion-weighted imaging of the rat optic nerve.

The apparent diffusion coefficient (ADC) of the rat optic nerve was measured in vitro, using magnetic resonance imaging, to determine the effects of changes in cellular volume fraction on the diffusion of tissue water. Nerve ADC was determined under conditions of cell membrane depolarization and (i) increased intracellular volume, (ii) decreased intracellular volume, and (iii) negligible volume change. Depolarization alone had little affect on ADC, whereas volume changes produced strong, reversible effects. Increased cell volume decreased ADC and vice versa. These results are consistent with the view that changes in the extracellular space are the major source of ADC changes in brain tissue.

Animals↗
PubMed1996

Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain.

A novel approach is presented for imaging macromolecule and metabolite signals in brain by proton magnetic resonance spectroscopic imaging. The method differentiates between metabolites and macromolecules by T1 weighting using an inversion pulse followed by a variable inversion recovery time before localization and spectroscopic imaging. In healthy subjects, the major macromolecule resonances at 2.05 and 0.9 ppm were mapped at a nominal spatial resolution of 1 x 1 x 1.5 cm3 and were demonstrated to be highly reproducible between subjects. In subacute stroke patients, a highly elevated macromolecule resonance at 1.3 ppm was mapped to infarcted brain regions, suggesting potential applications for studying pathological conditions.

Adult↗
PubMed1995

New magnetic resonance techniques for acute ischemic stroke.

Neuroimaging was revolutionized by the development of computed tomography (CT) and standard T1- and T2-weighted magnetic resonance imaging (MRI). Magnetic resonance imaging and CT can adequately distinguish hemorrhage from infarction and depict ischemic stroke 12 to 24 hours after onset. However, during the critical initial hours after the onset of ischemic stroke, these imaging technologies do not adequately demonstrate the location and extent of infarction. Diffusion-weighted MRI and perfusion imaging, as well as advances in magnetic resonance spectroscopy, will enhance our ability to evaluate ischemic stroke shortly after onset. Some of the uses of MRI techniques are as follows: (1) Diffusion-weighted imaging can depict the location and extent of the ischemic lesion as soon as a stroke patient is available for examination. (2) Perfusion imaging evaluates blood flow within the brain's microvasculature and can reveal regions of perfusion deficits corresponding to major vascular territories. (3) Magnetic resonance spectroscopy evaluates metabolic abnormalities associated with focal brain ischemia by specific biochemical measurements. These MRI techniques will rapidly provide important information to clinicians about ischemia, guiding diagnosis and helping in the development of acute stroke interventions to improve outcome.

Brain Ischemia↗
PubMed1995

Barbiturate-reversible reduction of water diffusion coefficient in flurothyl-induced status epilepticus in rats.

Rat brains (n = 17) with flurothyl-induced status epilepticus (SE) have been imaged with a gradient-echo diffusion-weighted imaging sequence at 2.0 T. The apparent water diffusion coefficient (ADC) decreased during seizure discharges. The magnitude of the ADC reduction correlated well with the duration of flurothyl exposure. A 17% reduction in the water ADC compared with preseizure condition was observed in rats with the longest flurothyl exposure time. In 13 rats, pentobarbital was used to arrest the electrographic seizure activity. ADC values began to return to normal a few minutes after the injection. In four rats with no pentobarbital administration, ADC values remained depressed up to 1 h after seizure onset. The results suggest that diffusion-weighted MR imaging may be useful for mapping recent intense seizure activity in human patients with medically intractable epilepsy.

Animals↗
PubMed1995

Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction.

BACKGROUND AND PURPOSE: We sought to determine whether lactate and N-acetyl signals measured by proton magnetic resonance spectroscopy (MRS) in the first days after stroke correlate with clinical measures of disability and functional outcome. METHODS: One-dimensional spectroscopic imaging was performed after stroke on 32 patients using a 2.1-T magnet. The Toronto Stroke Scale score at the time of the MRS study and the Barthel Index score at hospital discharge were determined from patient records. Lesion volume was estimated by a tracing algorithm from the scout magnetic resonance image obtained as part of the MRS study. The scaled lactate and N-acetyl signals from the voxel having the highest measured lactate were used to predict the clinical variables and lesion volume, as well as relative perfusion within the lesion, in those patients who underwent single-photon emission computed tomography (SPECT) blood flow imaging, using a multiple regression analysis. The correlation of lesion volume with the clinical variables was also evaluated. RESULTS: Lesion lactate signal was correlated with the Toronto Stroke Scale score, Barthel Index score, lesion volume, and SPECT score, all at P < .01. The N-acetyl level correlated with the Barthel Index score and lesion volume at P < .05. Lesion volume was also strongly correlated with the clinical variables (P < .0001). CONCLUSIONS: This is the first study to document the clinical predictive value of proton MRS measurements in patients after stroke. The association with functional outcome is stronger for lactate than for N-acetyl. Spectroscopic assessment of the metabolic status of cerebral tissues shortly after infarction may have significant clinical utility.

Acetates↗
PubMed1995

In vivo measurement of phenylalanine in human brain by proton nuclear magnetic resonance spectroscopy.

Disorders of the CNS are the major causes of morbidity and mortality observed in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe) in vivo would greatly enhance the ability to investigate both the pathophysiology and the efficacy of therapy of this aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance spectroscopic studies were performed in seven subjects with PKU using pulse sequences optimized to detect the aromatic protons of Phe. Ten control studies were also performed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was measured at the time of the spectroscopic examination in the PKU patients. A Phe signal was observed in all 12 studies performed on the group with PKU, and in five studies cerebral Phe concentrations were measured to be 480 to 780 mumol/g. Plasma Phe concentrations were 0.7 to 3.3 mM (10.8 to 54.8 mg/dL) in the subjects with PKU. Human cerebral Phe concentrations can be measured noninvasively using proton nuclear magnetic resonance spectroscopy. A simultaneous measure of Phe and several other cerebral metabolites is obtained with this innovative technology. Adaptations of this technique can be used to investigate PKU and other neurometabolic disorders with modifications of current clinical magnetic resonance imaging systems.

Adolescent↗
PubMed1994

BOLD MRI monitoring of changes in cerebral perfusion induced by acetazolamide and hypercarbia in the rat.

To evaluate MRI methods for estimating cerebrovascular reserve, we computed changes in the R2* and R2 transverse relaxation rate and apparent diffusion coefficient (ADC) at 2.0 Tesla in five rats after administration of 30 mg of acetazolamide and in four rats during inhalation of 20% carbon dioxide gas. Significant decreases in R2*, corresponding to increases in gradient echo MRI signals, occurred in both the acetazolamide (average change -8.3%, P = 0.005) and the carbon dioxide (-2.7%, P = 0.009) treated animals. The computed values for R2 and ADC were unchanged. The magnitude of the gradient echo MRI changes observed should permit anatomic mapping of blood flow reactivity patterns in normal human subjects and in patients at risk for cerebrovascular disease.

Acetazolamide↗
PubMed1994

Proton spectroscopy of human stroke: assessment of transverse relaxation times and partial volume effects in single volume steam MRS.

Proton T2 relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T2 values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T2 for lactate in patients was 780 +/- 257 ms, respectively (mean +/- SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T2, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.

Aged↗
PubMed1994

Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose.

Cerebral metabolism of D[1-13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1-13C]glucose in four healthy subjects. The use of three-dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution were sufficient to allow 4 min of time-resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution. [4-13C]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3-13C]glutamate clearly lagged behind that of [4-13C]-glutamate and peaked at t = 110-140 min. Multiplets due to homonuclear 13C-13C coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spectra acquired between 120 and 180 min yielded a 13C isotopic fraction at C4 glutamate of 27 +/- 2% (n = 4), which was slightly less than one-half the enrichment of the C1 position of plasma glucose (63 +/- 1%), p < 0.05. By comparison with an external standard the total amount of [4-13C]glutamate was directly quantified to be 2.4 +/- 0.1 mumol/ml-brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 +/- 0.7 mumol/ml, which agrees with previous estimates of total brain glutamate concentrations. The agreement suggests that essentially all of the brain glutamate is derived from glucose in health human brain.

Adult↗
PubMed1994

Nuclear magnetic resonance spectroscopy of seizure states.

Magnetic resonance spectroscopy (MRS) can be used for noninvasive measurement of more than two dozen small metabolites in the brains of living animals and humans. In the first decade of its use for study of seizure phenomena in animals, MRS successfully detected in vivo seizure-induced cerebral acidosis and reduction of phosphocreatine concentration, changes that had been described previously by techniques requiring destruction of tissue. Thus validated, MRS was used to reveal new aspects of epileptic pathophysiology in animals: (a) dissociation of brain lactate and pH during experimental status epilepticus of low and intermediate intensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phenomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain activation. Diffusion-weighted imaging of rat brain has shown that status epilepticus apparently shortens the mean path length of water diffusion, a novel finding that provides new insight concerning the physical conditions under which the seizure-related chemical changes detected by MRS occur. MRS study of epileptic patients has been undertaken more recently as instruments large enough for observations on humans have become available. Acidosis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N-acetylaspartate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis.

Animals↗
PubMed1993

Changes in water diffusion and relaxation properties of rat cerebrum during status epilepticus.

Diffusion-weighted (DW) imaging has been used to record changes associated with status epilepticus (SE) in rat brain. It was found that the apparent diffusion coefficient (ADC) of water in brain decreased 14-18% during SE, and it fell a further 20-22% when the animals were sacrificed. The transverse decay time constant T2* showed corresponding reductions, but no significant changes were seen in relaxation times T1 or T2 values. Changes in ADC in status epilepticus are similar to those seen in stroke and ischemia but occur under very different conditions of blood flow and metabolism.

Animals↗
PubMed1993

Metabolic assessment of a neuron-enriched fraction of rat cerebrum using high-resolution 1H and 13C NMR spectroscopy.

This study explored the utility of 1H and 13C magnetic resonance spectroscopy to study a neuron-enriched preparation made from rat cerebrum. The preparation contained high concentrations of N-acetylaspartate and gamma-aminobutyric acid and low concentrations of glutamine, indicating that it was in fact rich in neuronal cytosol. This was confirmed by immunohistochemical studies with antibodies to neuronal and glial markers. A method of metabolite quantification based on the creatine signal yielded metabolite concentrations similar to those of rat cerebrum, whereas concentrations based on the metabolite/protein ratio were five times lower, suggesting that much protein in the preparation was not associated with functioning cytoplasm. The metabolic competence of the preparation was assessed by quantitative measurements of its ability to convert 1-13C-glucose into lactate, glutamate, aspartate, and other metabolites under well oxygenated conditions for 30 min. Calculated from the creatine standard, the mean glycolytic rate was the same as in a synaptosomal preparation studied under similar conditions and the same as rat cerebrum in vivo. Tricarboxylic acid cycle flux occurred at half the rate observed in the synaptosomal preparation and 16% of the basal cerebral metabolic rate in vivo.

Alanine↗
PubMed1993

Early temporal variation of cerebral metabolites after human stroke. A proton magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy has documented declines in normal metabolites and long-term elevation of lactate signal after stroke in humans. Within days of stroke, leukocytes infiltrating the infarct zone may produce much of the lactate seen in the subacute and chronic periods. METHODS: We examined 10 patients by localized proton magnetic resonance spectroscopy with one-dimensional spectroscopic imaging within the first 60 hours after acute nonhemorrhagic cerebral infarction, a period before abundant leukocyte infiltration. Follow-up studies on day 8 to 17 after stroke were performed on 7 of these patients. RESULTS: Initially, the lactate magnetic resonance signal was elevated in all patients. The N-acetyl-aspartate peak within the lesion was reduced below contralateral normal brain in all but two. At subsequent examination, significant declines had occurred in lesion maximum lactate and N-acetyl-aspartate signals, with average changes of -36 +/- 11% per week and -29 +/- 9% per week, respectively. Declines in lesion creatine/phosphocreatine and in choline-containing compound peaks occurred in some patients but did not attain statistical significance for the group as a whole. Estimated lesion volume correlated positively with both total (r = .75, P = .012) and lesion maximum (r = .74, P = .015) lactate signal. CONCLUSIONS: Elevated lactate signal is reliably detectable by magnetic resonance spectroscopy after acute cerebral infarction in humans. Clearance of lactate occurs despite the potential contribution of lactate-producing leukocytes in the subacute stage. Delayed loss of N-acetyl-aspartate signal in second examinations suggests that late death of viable cells may occur within the first 2 weeks after cerebral infarction.

Acute Disease↗