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Biomedical subjects

M R Bendall

Publications and source records attributed to M R Bendall.

At least 19 recordsLinked to original sources
PubMed1994

Dissociation of adenosine levels from bioenergetic state in experimental brain trauma: potential role in secondary injury.

Intracellular bioenergetic state and extracellular adenosine levels were monitored in rat brain prior to and following traumatic brain injury (TBI) using phosphorus magnetic resonance spectroscopy and microdialysis, respectively. Fluid percussion-induced TBI (2.6 +/- 0.2 atm) resulted in significant reductions in free cytosolic [Mg2+], cytosolic [ATP]/[ADP] [P(i)], and delta GATP and elevations in cytosolic [ADP] and [5'-AMP]. Intracellular ATP concentration and pH did not change significantly after trauma. Mitochondrial capacity for oxidative phosphorylation (indexed by V/Vmax) increased significantly from approximately 0.45 prior to injury to approximately 0.58 following TBI. All metabolic changes were maximal at 2-3 h post-TBI. Conversely, extracellular adenosine concentrations increased transiently following TBI, with levels peaking at 10 min posttrauma, then declining rapidly to preinjury values by 50 min. Thus, despite pronounced long-term depression in bioenergetic status and a marked rise in [5'-AMP], formation and release of adenosine were elevated only transiently within the first hour following TBI. Since steady-state adenosine levels were essentially unchanged beyond 1 h posttrauma, mooted neuroprotective actions of endogenous adenosine would be minimized. Intracerebroventricular injections of 2-chloroadenosine (0.5 and 2.5 nmol) immediately prior to TBI dose-dependently attenuated metabolic disturbances and improved posttraumatic neurologic outcome (p < 0.05). The observations indicate that (a) TBI results in dissociation of adenosine release from intracellular bioenergetic state, a phenomenon possibly contributing to secondary injury following TBI; and (b) supplementing brain with an adenosine agonist attenuates irreversible injury.

2-Chloroadenosine↗
PubMed1994

Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be particularly effective in detecting early (0 to 4 hours) pathophysiological changes in localized brain regions after cerebral ischemia. The present study sought to establish whether diffusion-weighted MRI would be similarly effective in predicting outcome after traumatic brain injury. METHODS: Diffusion-weighted MRI images and T2-weighted MRI images were obtained over 4 hours after either moderate fluid percussion-induced traumatic brain injury or unilateral carotid ligation in rats. RESULTS: Diffusion-weighted MRI images of traumatic brain injury demonstrated focal regions of image hypointensity as early as 1 hour after trauma. The relative diffusion coefficient in these hypointense regions was significantly increased (P < .005) by 4 hours after trauma compared with the noninjured hemisphere, but only in the transverse plane in the x direction. In contrast, induction of diffuse, nonfocal ischemia by unilateral carotid ligation resulted in scattered regions of hyperintensity with a significant (P < .001) decrease in relative diffusion coefficient as early as 1 hour after ligation compared with the noninjured hemisphere. This decrease exhibited no directionality. CONCLUSIONS: We conclude that traumatic brain injury results in an increased water diffusion distance with the directionality indicative of bulk flow of extracellular fluid toward the lateral ventricles (vasogenic edema). In contrast, the decreased water diffusion distance with no apparent directionality observed in ischemia is most likely indicative of cytotoxic edema. Diffusion-weighted MRI therefore has the potential to differentiate cases of traumatic brain injury with no focal ischemia from those instances of traumatic brain injury in which focal ischemia is a complication.

Animals↗
PubMed1992

Selective intracellular lactate invisibility in Enterococcus faecalis.

In this article we will demonstrate that differences in Hahn T2 relaxation of the 1H NMR signal from cytosolic and extracellular lactate can be exploited to monitor lactate concentration gradients in bacterial cells and provide information on lactate transport mechanisms. As a by-product of this study we have determined that there are at least three pools of lactate in bacterial cells with differing visibility in the NMR experiment. This has serious implications for the spectral editing techniques that are so vital for in vivo spectroscopy.

Biological Transport↗
PubMed1989

Metabolic changes in rabbit spinal cord after trauma: magnetic resonance spectroscopy studies.

Combined phosphorus and proton magnetic resonance spectroscopy (MRS), using double-tuned surface coils, was used to monitor certain metabolic changes in the L-3 spinal segment of anesthetized rabbits prior to and following experimental spinal cord trauma. Following severe trauma, resulting in spastic paraplegia, there was a delayed and progressive accumulation of lactic acid, a decline in intracellular pH, and a loss of high-energy phosphates. Maximal alterations occurred between 2 and 3 hours after the trauma, with little further change by 4 hours. Histological examination 2 weeks after trauma showed tissue necrosis and cavitation. These findings support the concept of secondary tissue injury after spinal cord trauma and suggest that early changes in metabolism, as shown by MRS, may predict irreversible tissue damage.

Adenosine Triphosphate↗
PubMed1989

Magnetic resonance imaging with adiabatic pulses using a single surface coil for RF transmission and signal detection.

In order to overcome the problems that arise from nonuniform B1 fields, there has been interest in developing pulses that are insensitive to large variations in RF power. Pulses derived from adiabatic passage principles that can execute spin inversion, excitation, and 90 degrees and 180 degrees plane rotations in the presence of B1 inhomogeneities have recently been described. When driven with optimized modulation functions, these pulses can execute uniform excitation, refocusing, and slice-selective inversion over a 10-fold or greater variation in B1 magnitude. This insensitivity to B1 strength enables the execution of T1- and/or T2-weighted spin-echo imaging experiments using coils, such as the surface coil, with extremely inhomogeneous B1 profiles. We have successfully acquired images with these pulses at 200 MHz using a single surface coil as the transmitter and receiver. Images of the slice definition, the region over which the excitation and refocusing pulses operate with a surface coil, and brain images obtained with slice planes perpendicular to the plane of the surface coil are presented. Results demonstrate that these pulses can be transmitted with a surface coil to yield high-quality T1- and/or T2-weighted images without B1 artifacts.

Animals↗
PubMed1988

Calibrated uncoupling of tightly coupled concentric surface coils for in vivo NMR.

Three known active methods of detuning rf coils have been tested by determining the efficiency of uncoupling two concentric transmit surface coils in a double-coil probe. In a comparison at 80 MHz, the method based on the use of lambda/4 cables was found to have advantages. These methods utilize the introduction of an additional resonance at the frequency of interest to completely detune a coil. By offsetting the detuning of the coil (by offsetting the additional resonance) a calibrated fraction of the rf field of the detuned coil can be added to or substracted from the rf field of the neighboring coil.

Calibration↗
PubMed1988

In vivo assessment of focal brain lactate alterations with NMR proton spectroscopy.

Spectral editing techniques and localization of 1H signals were applied to monitor lactate accumulation in a circumscribed region of brain damage. The experiments were performed at 2.35 T (100 MHz) in a 40-cm bore magnet. Following unilateral craniectomy in anesthetized adult cats, a two-turn surface coil was positioned over the dural surface. Proton spectra were obtained before and 1-5 h after production of a cortical cold lesion from three curved shells of brain tissue, each approximately 3 mm thick. The localized spectrum was obtained from each region with and without spectral difference editing for the lactate CH3 protons, but always with the maximum excitation produced by the semiselective binomial pulse centered on the lactate CH3 resonance. Region 1 represented the damaged area, Region 2 was located immediately below Region 1, and Region 3 was immediately below Region 2. Spin-echo magnetic resonance imaging was used to confirm the relationship between the location of the lesion and the regions from which the spectra were obtained. Spectra obtained without lactate editing showed, in addition to the N-acetylaspartate peak, a large lactate peak in Region 1 after production of the cold lesion. In Regions 2 and 3, changes in lactate were more difficult to assess owing to the presence of a lipid peak at a similar frequency that results from incomplete suppression by the spin-echo pulse sequence alone. Spectra acquired using lactate editing did not contain the lipid peak and clearly showed relatively small lactate accumulations in Regions 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Traumatic brain injury in the rat: alterations in brain lactate and pH as characterized by 1H and 31P nuclear magnetic resonance.

Application of both phosphorus (31P) and proton (1H) magnetic resonance spectroscopy (MRS) to the study of brain metabolism permits the noninvasive measurement of intracellular pH and brain lactate level. We have used water-suppression 1H MRS with novel lactate-editing techniques, together with 31P MRS, to characterize sequential changes in brain lactate level and pH in vivo over an 8-h period following fluid-percussion brain injury of graded severity in the rat. A transient fall in intracellular pH (from 7.09 +/- 0.07 at baseline to 6.88 +/- 0.09 at 40 min postinjury) occurred in animals subjected to moderate- (1.5-2.2 atm) and high- (2.5-3.3 atm) but not low-level (0.1-1.2 atm) injury; intracellular pH returned to baseline by 90 min postinjury. Transient elevations in brain lactate level were observed that temporally paralleled and were significantly correlated with the pH changes for all injury levels (r = 0.93, p less than 0.001). Postinjury alterations in intracellular brain pH and lactate level were identical in magnitude in animals subjected to either moderate or high-level injury. However, animals subjected to moderate injury had a moderate chronic neurological deficit that persisted up to 4 weeks postinjury, whereas animals subjected to a high level of injury showed greater histopathological damage and a more severe chronic neurological deficit. These data suggest that the extent of posttraumatic intracellular cerebral acidosis in our model of experimental head injury is not directly related to the severity of functional neurological deficit.

Animals↗
PubMed1985

Application of multipulse NMR to observe 13C-labeled metabolites in biological systems.

Limitations in resolution and sensitivity of 13C NMR spectroscopy have reduced the information obtainable from intact biological systems. With the aim of increasing the information from in vivo 13C NMR two multipulse NMR techniques, the DEPT pulse sequence and the gated spin-echo sequence, were used to obtain edited 13C NMR spectra from different 13C-labeled mammalian tissues. This allowed the separation of the 13C NMR signals from the tissues into subspectra containing either CH, CH2, or CH3 signals, thereby increasing the information obtainable from these spectra. Comparing the two techniques, the DEPT sequence gives more accurate editing than the gated spin-echo sequence but suffers from the difficulty of determining 1H pulse angles in vivo.

Acetates↗
PubMed1985

Theoretical description of depth pulse sequences, on and off resonance, including improvements and extensions thereof.

A general mathematical description of depth pulse sequences in terms of rotation matrices permits a single matrix, known as a cycle matrix, to be written down for each phase-cycled pulse in the overall sequence, such that the result for the total phase-cycled sequence is the product of the individual cycle matrices. It is straightforward to include the effect of the tilted rf axis off resonance and obtain exact solutions. The two types of phase-cycled pulse used in a depth pulse scheme are 2 theta [+/- x] and 2 theta [+/- x, +/- y] and for the general off-resonance case, four of the off-diagonal elements in the 2 theta [+/- x] cycle matrix, and all of the off-diagonal elements in the 2 theta [+/- x, +/- y] cycle matrix, are zero. These simplifications enable important improvements of depth pulse schemes for the elimination of high-flux signals, the reduction of signals from sample regions experiencing pulse angles differing from 90 degrees, and the avoidance of deleterious off-resonance effects such as the production of dispersion signals. In all cases, the dependence of signal intensity off resonance can be easily and exactly calculated. There are important applications in in vivo spectroscopy.

Magnetic Resonance Spectroscopy↗
PubMed1985

Sensitive-volume localization for in vivo NMR using heteronuclear spin-echo pulse sequences.

Heteronuclear spin-echo techniques, which require the application of an inversion pulse on the second heteronucleus, may be applied with inhomogeneous rf coils such as surface coils. There are important applications in vivo including the detection of 13C-labeled and 15N-labeled metabolites in the 1H NMR spectrum. Using a depth pulse scheme for the 1H spin-echo sequence, and particular single or composite 13C pulses, two sensitive volumes are generated by the 1H and the 13C rf coils and signal is only obtained from the region of overlap between the two sensitive volumes. This method of signal localization for in vivo applications can be extended to 1H homonuclear editing and selective polarization-transfer techniques. The off-resonance characteristics of several different composite pulses are explored.

Animals↗
PubMed1985

Theory of localized polarization transfer.

Because polarization transfer from one type of nucleus to another can occur only when both types of nuclei are excited, it is possible, by using two separate rf coils for the excitation, to restrict the spatial region of the sample from which a signal can be received to a specific volume of overlap of the two inhomogeneous field patterns. In this paper we develop the theory of this method of localization in a homogeneous static field. The polarization transfer is achieved by a generalized phase-cycled DEPT sequence, in which case the method has the additional advantage of a gain in sensitivity of a 13C signal associated with the maximum polarization-transfer enhancement. Localization by means of the inverse-DEPT sequence is also studied, and off-resonance effects are calculated. Experimental confirmation of the theoretical expressions is given.

Magnetic Resonance Spectroscopy↗
PubMed1985

1H-Observe/13C-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo.

We have used (13C)-1H NMR spectroscopy at 360.13 MHz to resolve the 13C coupled proton resonance of glutamate and lactate in the rat brain in vivo. The time required for the 13C fractional enrichment of the 4-CH2 position of brain glutamate to reach isotopic steady state was determined during a continuous infusion of D-[1-13C]glucose. Under conditions of ischemia, measurements made of the 3-CH3 of lactate in (13C)-1H NMR spectra revealed the relative contribution of brain glucose and glycogen to lactate formation. (13C)-1H NMR was 11 times more sensitive than 13C NMR for the detection of 13C in the 3-CH3 position of lactate and 6 times more sensitive for the detection of 13C in the 4-CH2 of glutamate under similar in vivo conditions.

Animals↗
PubMed1984

Estimation of H+ to adenosine 5'-triphosphate stoichiometry of Escherichia coli ATP synthase using 31P NMR.

High-field 31P NMR techniques have been used to measure transmembrane delta pH in wild-type, unc A, and hem A mutants of Escherichia coli. delta psi was measured by distribution methods with radioactive tetraphenylphosphonium bromide and 86Rb+ ions as the probes, while intracellular ATP, ADP, and inorganic phosphate concentrations were determined from the 31P NMR spectra. delta G'p and the stoichiometry for ATP synthesis [delta G'p/(F delta p)] were then calculated. The stoichiometry of the ATP synthase was found to vary as a function of the cellular metabolic state. In nongrowing, wild-type cells delta p was 192 +/- 16 mV with succinate as the substrate and saturating oxygen tension. With limiting oxygen (congruent to microM oxygen), delta p was 125 +/- 14 mV. Nucleoside triphosphate synthesis was observed in both cases. The H+/ATP stoichiometry varied from 2.15 +/- 0.35 under aerobic conditions to 3.6 +/- 0.8 at low oxygen tension. delta p for unc A cells was 140 +/- 14 mV with glucose as the substrate (greater than 2.5 microM oxygen) and for hem A mutants was 115 +/- 10 mV. The bulk phase potentials in oxygen-limited, wild-type cells and in respiratory deficient (hem A) cells are comparable, but in the former the ATPase is poised for synthesis while in the latter it generates delta p. The data support a role for localized interactions between the redox and the ATPase sites.

ATP Synthetase Complexes↗
PubMed1984

Depth pulse sequences for surface coils: spatial localization and T1 measurements.

The depth pulse sequences theta;[2 theta(+/- x, +/- y)]2 and 2 theta;theta(+/- x);[2 theta(+/- x, +/- y)]2 have been implemented with a 20 mm diameter two-turn surface coil operating at 31P resonance (89.96 MHz). In these sequences theta refers to the pi/2 rf pulse at the center of the sensitive region of the coil, +/- x and +/- y denote the four orthogonal phases of the rf pulses, and ";" represents an optional brief delay (e.g., 4 microseconds) between pulses to facilitate switching between different phases. Localization of the sensitive region was demonstrated with phantom samples by in vivo monitoring of rat livers and detection of necrotic regions of subcutaneously implanted tumors. The inversion-recovery pulse sequence, 2 theta-tau-theta(+/- x);[2 theta(+/- x, +/- y)]2, where tau is a variable delay, was employed to measure the spin-lattice relaxation time of a selected region, which could be varied by changing the pulse width and the size of the surface coil.

Animals↗
PubMed1983

High-field phosphorus NMR studies of the stoichiometry of the lactate/proton carrier in Streptococcus faecalis.

High-field 31P-NMR studies of whole cells of Streptococcus faecalis have shown that delta pH can be formed by ATP hydrolysis and also by lactate transport. We have used 31P-NMR to measure the pH dependence of the variable stoichiometry of the proton/lactate carrier. At low external pH (pH approximately equal to 6.5) the influx stoichiometry was 1.1 H+/lactate, while at high pH (7.5) the ratio was almost 2; the apparent midpoint pH of this variable stoichiometry is 7. delta psi measurements support the electrogenic nature of lactate transport at high pH; the variable rate of membrane depolarization caused by lactate transport also had a midpoint near pH 7.0. The data is consistent with a symmetrical carrier operating with variable stoichiometry as proposed by Michels et al.

Biological Transport↗