Biomedical subjects

J S Leigh

Publications and source records attributed to J S Leigh.

At least 19 recordsLinked to original sources

PubMed1992

Electron paramagnetic resonance studies of a ras p21-MnIIGDP complex in solution.

The number of water molecules bound to Mn2+ in the complex with a variant of Ha ras p21 and GDP has been determined by electron paramagnetic resonance (EPR) measurements in 17O-enriched water. A resolution enhancement method has been used to improve quantitation of the spectral data. These spectroscopic measurements show that Mn2+ has four water ligands in this complex, a result in agreement with the conclusions of a previous paper [Smithers, G. W., Poe, M., Latwesen, D. G., & Reed, G. H. (1990) Arch. Biochem. Biophys. 280, 416-420]. The resolution enhancement method has also been applied in a measurement of the 17O-Mn2+ superhyperfine coupling constant of 17O in the beta-phosphate of the GDP in the ras p21 complex. The intrinsically narrow EPR signals of Mn2+ in the complex with ras p21 and GDP in 2H2O respond to resolution enhancement such that the superhyperfine splitting from the 17O nuclear spin (I = 5/2) becomes visible in the EPR signals. An 17O-Mn2+ superhyperfine coupling constant is obtained from simulation of the resolution-enhanced EPR spectrum.

Electron Spin Resonance Spectroscopy↗

PubMed1992

Magnetic resonance imaging of perfusion using spin inversion of arterial water.

A technique has been developed for proton magnetic resonance imaging (MRI) of perfusion, using water as a freely diffusable tracer, and its application to the measurement of cerebral blood flow (CBF) in the rat is demonstrated. The method involves labeling the inflowing water proton spins in the arterial blood by inverting them continuously at the neck region and observing the effects of inversion on the intensity of brain MRI. Solution to the Bloch equations, modified to include the effects of flow, allows regional perfusion rates to be measured from an image with spin inversion, a control image, and a T1 image. Continuous spin inversion labeling the arterial blood water was accomplished, using principles of adiabatic fast passage by applying continuous-wave radiofrequency power in the presence of a magnetic field gradient in the direction of arterial flow. In the detection slice used to measure perfusion, whole brain CBF averaged 1.39 +/- 0.19 ml.g-1.min-1 (mean +/- SEM, n = 5). The technique's sensitivity to changes in CBF was measured by using graded hypercarbia, a condition that is known to increase brain perfusion. CBF vs. pCO2 data yield a best-fit straight line described by CBF (ml.g-1.min-1) = 0.052pCO2 (mm Hg) - 0.173, in excellent agreement with values in the literature. Finally, perfusion images of a freeze-injured rat brain have been obtained, demonstrating the technique's ability to detect regional abnormalities in perfusion.

Animals↗

PubMed1992

Perfusion imaging.

Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies.

Animals↗

PubMed1992

Hadamard spectroscopic imaging technique as applied to study human calf muscles.

In vivo results obtained by the B1 insensitive Hadamard spectroscopic imaging multivolume technique used with a surface coil are shown. The functional behavior of different human calf muscles during exercise was determined and the Pi/PCr ratio in each calf muscle, during steady-state conditions, was measured as a function of work level. Different levels of metabolic and physical activity were observed at the three calf muscles.

Humans↗

PubMed1992

Sensitivity of in vivo MRS of the N-delta proton in proximal histidine of deoxymyoglobin.

The sensitivity of in vivo MRS of the N-delta proton of the proximal histidine of deoxymyoglobin in human skeletal muscles is discussed. Longitudinal relaxation time T1 of this deoxymyoglobin signal was measured in cuffed human forearms at 1.5 T and found to be 9.9 ms. Deoxymyoglobin spectra can be obtained from a forearm in seconds. The detection sensitivity of deoxymyoglobin in fully ischemic skeletal muscles and that of 31P MRS of PCr in normal resting muscles are compared.

Adult↗

PubMed1992

Investigation of stroke in sickle cell disease by 1H nuclear magnetic resonance spectroscopy.

Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atrophic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal-appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids.

Adolescent↗

PubMed1992

Muscle metabolism in track athletes, using 31P magnetic resonance spectroscopy.

We tested whether preferred running event in track athletes would correlate with the initial rate of phosphocreatine (PCr) resynthesis following submaximal exercise. PCr recovery was measured in the calf muscles of 16 male track athletes and 7 male control subjects following 5 min of repeated plantar flexion against resistance. Pi, PCr, and pH were measured using phosphorus magnetic resonance spectroscopy (31P MRS) with an 8-cm surface coil in a 1.8-T magnet. During exercise, work levels were gradually increased to deplete PCr to 50-60% of the initial value. No drop in pH was seen in any of the subjects during this exercise. The areas of the PCr peaks following exercise were fit to monoexponential curves. Two or three tests were performed on each subject and the results averaged. Athletes were divided into three groups based on their primary event: sprinters running 400 m or less, middle-distance athletes running 400-1500 m, and long-distance athletes running farther than 1500 m. The maximal rates of PCr resynthesis (mmol.min-1.kg-1 muscle weight) were 64.8 +/- 8.6, for long-distance runners; 41.4 +/- 11, for middle-distance runners; 32.0 +/- 7.0, for sprinters; and 38.6 +/- 10, for controls (mean +/- SE). The faster PCr recovery rates seen in long-distance runners compared with sprinters indicate greater oxidative capacity, which is consistent with the known differences between athletes in these events.

Adolescent↗

PubMed1991

Metabolic heterogeneity in human calf muscle during maximal exercise.

Human skeletal muscle is composed of various muscle fiber types. We hypothesized that differences in metabolism between fiber types could be detected noninvasively with 31P nuclear magnetic resonance spectroscopy during maximal exercise. This assumes that during maximal exercise all fiber types are recruited and all vary in the amount of acidosis. The calf muscles of seven subjects were studied. Two different coils were applied: an 11-cm-diameter surface coil and a five-segment meander coil. The meander coil was used to localize the 31P signal to either the medial or the lateral gastrocnemius. Maximal exercise, consisting of rapid plantar flexions, resulted in an 83.7% +/- 7.8% decrease of the phosphocreatine pool and an 8-fold increase of the inorganic phosphate (Pi) pool. At rest the Pi pool was observed as a single resonance (pH 7.0). Toward the end of the first minute of exercise, three subjects showed three distinct Pi peaks. During the second minute of exercise the pH values stabilized at 7.12 +/- 0.12, 6.63 +/- 0.15, and 6.27 +/- 0.23. The same pattern was seen when the signal was collected from the medial or lateral gastrocnemius. In four subjects only two distinct Pi peaks were observed. The Pi peaks had differing relative areas in different subjects, but they were reproducible in each individual. This method allowed us to study the appearance and disappearance of the different Pi peaks, together with the changes in pH. Because multiple Pi peaks were seen in single muscles they most likely identify different muscle fiber types.

Adenine Nucleotides↗

PubMed1991

Longitudinal spin-order-based pulse sequence for lactate editing.

A new pulse sequence which edits proton spectra of lactate with full signal return and gives good suppression of water and fat signals is described. This sequence exploits longitudinal spin-order from lactate to edit lactate from fat. Experimental results from phantoms and excised pig heart are presented.

Animals↗

PubMed1990

Measurement of regional cerebral blood flow in cat brain using intracarotid 2H2O and 2H NMR imaging.

Cerebral blood flow (CBF) was measured in cat brain in vivo at 2.7 T using 2H NMR to monitor the washout of deuterated saline injected into both carotid arteries via the lingual arteries. In anesthetized cats, global CBF varied directly with PaCO2 over a range of 20-50 mm Hg, and the corresponding global CBF values ranged from 25 to 125 ml.100 g-1.min-1. Regional CBF was measured in a 1-cm axial section of cat brain using intracarotid deuterated saline and gradient-echo 2H NMR imaging. Blood flow images with a maximum pixel resolution of 0.3 x 0.3 x 1.0 cm were generated from the deuterium signal washout at each pixel. Image derived values for CBF agreed well with other determinations, and decreased significantly with hypocapnia.

Animals↗

PubMed1990

In vivo MRS measurement of deoxymyoglobin in human forearms.

In vivo MRS measurement of deoxymyoglobin (deoxy-Mb) in human forearms was performed by observing the N-delta proton of F8 proximal histidine. The concentration of deoxy-Mb reflects the oxygen level in the muscle. In resting muscles, the deoxy-Mb level was below the detection sensitivity. When ischemia was introduced by arterial occlusion, the time-resolved NMR spectra (with 1 min resolution) was recorded to follow the change in the deoxy-Mb signal. The result shows that deoxy-Mb signal builds up and levels off within 6 min. This technique may be used to study bioenergetics of muscle during exercise and under pathological conditions.

Forearm↗

PubMed1989

The synthesis of pulse sequences yielding arbitrary magnetization vectors.

A new procedure and algorithm are presented to allow the synthesis of a pulse sequence which will generate an arbitrary frequency-dependent spin excitation. This procedure is a generalization of our previous paper, where this was done subject to the restriction that the spin excitation was symmetric about zero offset frequency, and pulses were restricted to being about a fixed axis. The required final z-magnetization vector (Mz) is expressed as a function of the off-resonance frequency as an Nth order complex Fourier series. We then form a consistent Fourier series for (Mxy). As many as 2(2)N different pulse sequences may be directly generated all of which produce a different Mxy(f), but the same Mz(f). A pulse sequence is then generated which will yield the desired Mz(f) and Mxy(f). This is done by an analytic inversion of the Bloch equation, not by the classical Fourier approximation. This technique enables us to generate any Mz which is potentially realizable by a pulse sequence.

Algorithms↗

PubMed1989

The use of finite impulse response filters in pulse design.

We develop a new way of synthesizing pulse sequences with desirable frequency characteristics. By combining our previous results with techniques from the theory of finite impulse response filters, we can specify (1) the total duration of the pulse sequence, (2) the frequency ranges it is desired to perturb, (3) the desired perturbation, and (4) the frequency range it is desired not to perturb. We can then synthesize a hard pulse sequence which will yield that desired perturbation with the minimal possible error. The minimum error is global, in the sense that no pulse sequence can do better at achieving the specifications, and is not just a local minimum, around the pulse sequences close to the derived pulse.

Algorithms↗

PubMed1989

The synthesis of soft pulses with a specified frequency response.

We propose a new approach to synthesizing shaped pulses, by first synthesizing a hard pulse sequence and then converting it to a soft pulse. In previous papers, we developed a new approach to synthesizing hard pulse sequences by exactly inverting the Bloch equation, which yields the optimal frequency response. These results can now be applied to shaped pulses. Specifically, one can specify (1) the total duration of the pulse, (2) the frequency range it is desired to perturb, (3) the perturbation desired and, (4) the frequency range it is desired not to perturb. One can then synthesize a shaped pulse which has the desired effect with the least possible error. This enables us to obtain very sharp inversion and pi/2 pulses.

Algorithms↗

PubMed1989

The application of spinors to pulse synthesis and analysis.

We show how spinors may be used to solve many problems in pulse synthesis and analysis. They provide an elegant simple notation for many problems. We show how one can specify the component of a spinor and then, by exactly solving the Bloch equations, synthesize a hard pulse sequence or a soft pulse which will yield the desired spinor. This is done by generalizing our previous approach to inverting the Bloch equations. This can be applied to synthesizing refocusing pulses. Finally, some simple consequences about symmetric pulses are derived. It is shown that given a symmetric inversion pulse, one can always synthesize an asymmetric inverting pulse of the same duration, which, as an inversion, is better.

Humans↗

PubMed1989

Muscle bio-energetics in acute glycolytic block: in vivo phosphorus-nuclear magnetic resonance study of iodo-acetate injected rats.

In vivo phosphorus nuclear magnetic resonance spectroscopy of muscle was performed at rest, during work and during postexercise recovery in rats injected with iodo-acetate (IA) (35-40 mg.kg-1, intra-arterially), in order to follow bio-energetic changes in muscle with acute glycolytic block. Three animals with contracture had very low ratios of phosphocreatine:inorganic phosphate (PCr:Pi) at rest (0.5-0.9). The PCr:Pi were normal at rest (6.9 +/- 2.0, +/- 2 SD) in all other rats. Exercise-induced continuous accumulation of phosphomonoesters (PME), the characteristic finding of glycolytic block, was observed. The end-exercise levels of PME correlated with the degree of block measured in vitro. During steady-state work, induced by nerve stimulation at four frequencies, PCr:Pi values were significantly lower (p less than 0.02) than the control values at 0.25, 1.0 and 2.0 Hz. The ATP levels fell during exercise to reach 75% +/- 7% of initial values. The recovery of PCr:Pi from exercise and the disappearance of PME were slow. Two animals which survived the IA injection demonstrated much lower PME accumulation 18 h later. It is concluded that in acute muscle glycolytic block: (1) energy metabolism is impaired during exercise and also at rest, (2) accumulating PME can serve as an indicator of the degree of glycolytic block, (3) ATP levels fall during work, and (4) postexercise recovery is slow. The findings are compared with 31P-NMR observations in chronic muscle glycolytic disorders.

Adenosine Triphosphate↗

PubMed1989

Effects of ovariectomy on energy metabolism in exercising rat muscle studied by 31P-NMR.

The effects of ovariectomy on metabolism of high-energy phosphate compounds during and after exercise were studied in hindleg muscles of 14 rats. Sciatic nerve stimulation was used to establish different work loads, and the changes in inorganic phosphate-to-phosphocreatine ratios (Pi/PCr) were recorded by 31P nuclear magnetic resonance (NMR) in vivo. Four weeks after ovariectomy, there was evidence of significantly higher Pi/PCr during work at stimulation rates greater than 0.5 Hz. The slope for the stimulation rate-to-Pi/PCr relationship decreased from 1.98 +/- 0.15 to 1.36 +/- 0.2 Hz/Pi/PCr after ovariectomy. The normalized tension output of these muscles, tested separately using identical stimulation protocols, was not changed with ovariectomy. Thus the relationship between work (tension-time integral) and bioenergetic cost (Pi/PCr) suggested reduced maximal enzyme activity (Vmax) by 9-17% as a result of lack of ovarian sex hormones, but no change in Michaelis-Menten constant (Km) was found. Postexercise recovery was also significantly slower (3.27 +/- 0.54 PCr/Pi units per minute compared with 4.04 +/- 1.08 in controls). It is suggested that reduced levels of ovarian sex hormones decrease oxidative phosphorylation. Cytochrome oxidase activity was reduced in these muscles by 40%, but other mitochondrial enzyme systems may be affected as well. The possible significance of these data is the implication of a reduced capacity for menopausal women or amenorrheic female athletes to perform prolonged intensive exercise.

Adenosine Triphosphate↗

PubMed1988

Triple nuclear NMR studies of cerebral metabolism during generalized seizure.

Noninvasive NMR spectroscopy of 1H, 31P, and 23Na is performed simultaneously to study brain metabolism during grand mal seizures. Decreases in PCr and increases in lactate associated with seizure as well as an intracellular shift of the Na+ ion pool are demonstrated. A close correlation between the phosphate potential and the intensity of the seizure, as well as the intra/extracellular ionic gradient, is shown.

Adenosine Diphosphate↗