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Biomedical subjects

J A Detre

Publications and source records attributed to J A Detre.

13 recordsLinked to original sources

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

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

Measurement of brain perfusion by volume-localized NMR spectroscopy using inversion of arterial water spins: accounting for transit time and cross-relaxation.

The theoretical model for perfusion measurement by NMR using arterial labeling of endogenous water is extended to include the effects of transit time and cross-relaxation of tissue water with macromolecules. Water magnetization in rat brain is monitored using the STEAM method to simultaneously determine the transit time, magnetization transfer rate constant, and perfusion. The results show that the transit time in rat brain is quite short, and thus its effect on perfusion measurement is small. It is also demonstrated both theoretically and experimentally that the steady-state effects of cross-relaxation with macromolecules on perfusion measurement are accounted for by a proper control experiment.

Animals

Proton magnetic resonance spectroscopy of pediatric brain tumors.

1H magnetic resonance spectroscopy allows the regional quantitation of a number of metabolites from the brain in a noninvasive fashion. Spectra were obtained from 5 normal children and 25 children with brain tumors. Choline (Cho), N-acetylaspartate (NAA), creatine and phosphocreatine, and lactate were quantitated in the form of ratios. The brains of normal children showed relatively high concentrations of Cho and NAA and virtually no lactate, as has been shown in adults. Benign astrocytomas and ependymomas were characterized by an elevation of the Cho:NAA ratio and an abnormal accumulation of lactate. Intrinsic malignant tumors were remarkable for an even higher Cho:NAA ratio but had no more lactate than was found in the benign tumors. Proton magnetic resonance spectroscopy may prove useful in characterizing neoplastic tissue in conjunction with more conventional imaging modalities.

Adolescent

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

Regional variation in brain lactate in Leigh syndrome by localized 1H magnetic resonance spectroscopy.

Localized water-suppressed 1H magnetic resonance spectroscopy was performed in an 11-month-old infant with Leigh syndrome. Spectra obtained from the basal ganglia, occipital cortex, and brainstem showed elevations in lactate, which were most pronounced in regions where abnormalities were seen with routine T2-weighted magnetic resonance imaging. This approach has allowed us to examine metabolism in brain tissue directly and noninvasively, and may provide a sensitive means for evaluating metabolic disease and the response to therapy in the brain.

Brain

Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan's disease: a case report.

The neuroradiological evaluation of Canavan's disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan's disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter.

Amidohydrolases

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

Measurement of cerebral blood flow in rat brain by 19F-NMR detection of trifluoromethane washout.

The washout of trifluoromethane (CHF3) from rat cerebral cortex was monitored by 19F NMR. After 15 min of inhalation of 67% CHF3/33% O2 the fluorine signal detected was in a steady state. The CHF3 was switched off rapidly at the endotracheal tube and the washout detected with 12-s time resolution. Two models were used to extract flow information, a simple exponential fit and a model which accounts for arterial CHF3 recirculation. In both cases, a two-compartment model fit the data significantly better than a one-compartment model. In both models, the faster time component varied with increasing pCO2, but no significant change in the slow component was detected. At control values of pCO2, there was a small difference in washout rate constants derived from the two models. At high pCO2, when tissue washout was comparable to arterial washout of CHF3, the model which accounted for arterial recirculation gave higher flows. Using this two-compartment model with correction for recirculation, a control flow (pCO2 = 35 mm Hg) of 0.73 +/- 0.04 ml/min/g was measured. Increasing plasma pCO2 increased the apparent flow six- to sevenfold with a 4.4% increase in flow per millimeter of Hg change in CO2. These results are qualitatively in agreement with results found by others using the washout of 133Xe. However, this method yields values for flow that are lower than those obtained using 133Xe washout, probably because of diffusion limitations of CHF3.

Animals

Nuclear magnetic resonance determination of flow, lactate, and phosphate metabolites during amphetamine stimulation of the rat brain.

The effects of amphetamine on rat cerebral blood flow, lactate, and phosphate levels were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Proton NMR imaging was used to determine the region of brain being studied. Blood flow was estimated by detecting the washout of trifluoromethane using 19F NMR. A dose of 20 mg/kg D-amphetamine sulphate stimulated flow fourfold over control values for at least 1 h. Even though amphetamine stimulated a large increase in flow, there were no significant changes in levels of inorganic phosphate, ATP, phosphocreatine, pH or Mg2+ as determined by 31P NMR. This was true for doses of 10 and 20 mg/kg D-amphetamine sulphate. No significant changes occurred in 1H NMR detected levels of lactate with a 20 mg/kg dose of amphetamines. Lactate levels increased slightly 30 min after administration of 10 mg/kg D-amphetamine sulphate. The results call into question the central role of changes in levels of phosphates in coupling increased cortical activity to increases in metabolism.

Amphetamine

Absence of pH changes during altered work in the in vivo sheep heart: a 31P-NMR investigation.

Saturation transfer from gamma-ATP to inorganic phosphate was used to assign the intracellular inorganic phosphate resonance of the phosphorus-31 nuclear magnetic resonance spectrum of heart obtained from adult sheep under Halothane anesthesia. The 31P chemical shift of intracellular inorganic phosphate was then used as a probe of myocardial pH. Resting myocardial pH was found to be 7.03 +/- 0.02. The effects of increasing myocardial work on myocardial pH were examined using external pacing and phenylephrine infusion alone or in combination to produce steady-state increases in the rate-pressure product. No alteration in myocardial pH was observed with up to 4-fold increases in rate-pressure product. No changes in high-energy phosphates were observed except at the highest rate-pressure products obtained, where small increases in inorganic phosphate and decreases in the phosphocreatine/ATP ratio were observed. In addition, the transition to a new steady state was studied with a 20-s time resolution after initiation of pacing. Again, no changes in pH or levels of phosphates were detected during the transition to increased work.

Adenosine Triphosphate

31P NMR measurements of myocardial pH in vivo.

A 31P NMR magnetization transfer method for measuring myocardial pH in vivo is demonstrated in the lamb, dog and cat. The method involves measuring the difference in chemical shift between the resonances of phosphocreatine and inorganic phosphate in magnetization transfer difference spectra in which the gamma-phosphate resonance of ATP has been saturated. The method has been verified by measuring the chemical shift difference between the resonances of 2-deoxyglucose 6-phosphate and phosphocreatine following infusion of the animals with 2-deoxyglucose. The measured pH values are significantly lower than those obtained in previous studies on the heart in vivo.

Animals