Jan Mintorovitch

Diffusion-weighted magnetic resonance imaging of acute focal cerebral ischemia : comparison of signal intensity with changes in brain water and Na+, K+-ATPase activity

Diffusion-weighted magnetic resonance (MR) images from rats during acute cerebral ischemia induced by middle cerebral artery occlusion were analyzed for correspondence with changes in brain water, cation concentrations, and Na+,K+-ATPase activity measured in vitro after 30 or 60 min of ischemia. In the ischemic hemisphere, signal intensity was increased at 30 min (p < 0.05 vs contralateral hemisphere) and further increased at 60 min. Na+,K+-ATPase activity was 34% lower in ischemic cortex and 40% lower in ischemic basal ganglia after 30 min (p < 0.05), but water content and Na+ and K+ concentrations were not significantly different between hemispheres. After 60 min, water content and Na+ concentration were increased, and both Na+,K+-ATPase activity and K+ concentration were decreased in the ischemic hemisphere (p < 0.05). These findings are consistent with the hypothesis that the early onset of signal hyperintensity in diffusion-weighted MR images may reflect cellular edema associated with impaired membrane pump function. Early in vivo detection and localization of potentially reversible ischemic cerebral edema may have important research and clinical applications.

Alterations in T1 of normal and reperfused infarcted myocardium after Gd‐BOPTA versus GD‐DTPA on inversion recovery EPI

This study tested whether Gd‐BOPTA/Dimeg or Gd‐DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd‐BOPTA is increased by weak binding to serum albumin. Thirty‐six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). ΔR1 was repeatedly measured over 30 min. Gd‐BOPTA caused greater ΔR1 for blood and myocardium than did Gd‐DTPA clearance of both agents from normal and infarcted myocardium was similar to blood clearance; plots of ΔR1myocardium/ΔR1blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd‐DTPA and Gd‐BOPTA, respectively, in reperfused infarction. The high value for Gd‐BOPTA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd‐BOPTA/Dimeg causes a greater ΔR1 than Gd‐DTPA in regions which contain serum albumin.

Relationship between extracellular neurotransmitter amino acids and energy metabolism during cerebral ischemia in rats monitored by microdialysis and in vivo magnetic resonance spectroscopy

The time-course of changes in extracellular glutamate and energy metabolism during 30 or 60 min of complete cerebral ischemia and 60-90 min of reperfusion was investigated by microdialysis and magnetic resonance spectroscopy in parallel groups of rats. During the first 10 min of ischemia, adenosine triphosphate (ATP) was completely depleted, and lactate increased 10-fold; after 30 min, intracellular pH had decreased to 6.33 +/- 0.11. ATP and lactate did not change further between 30 and 60 min of ischemia. Glutamate increased 30-fold between 10 and 30 min of ischemia and continued to increase in the 60-min ischemia group. After 30 min of reperfusion, glutamate had returned to pre-ischemic levels in both groups. The cellular energy state recovered within 50-60 min after 30 min of ischemia but never returned to more than 60% of baseline values after 60 min of ischemia. The continued increase in extracellular glutamate after total depletion of ATP suggests that glutamate release during ischemia is not entirely energy dependent. Ca(2+)-independent glutamate release and failure of energy-dependent glutamate re-uptake mechanisms may result in continued increase in extracellular glutamate. The rapid normalization of extracellular glutamate after 30 and 60 min of ischemia despite differences in the recovery of energy metabolism suggests that the glutamate levels were reduced by an energy-independent mechanism, such as diffusion into the restored circulation.

NG-Nitro-l-Arginine Delays the Development of Brain Injury During Focal Ischemia in Rats

BACKGROUND AND PURPOSE The present study was designed to determine the effect of nitro-L-arginine, the inhibitor of nitric oxide synthesis, on the evolution of cytotoxic brain edema during focal cerebral ischemia. METHOD Diffusion-weighted and contrast-enhanced, perfusion-sensitive magnetic resonance imaging was performed in anesthetized, mechanically ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusion of the middle cerebral artery combined with coagulation of the basilar artery. At the onset of ischemia, the animals were infused intravenously with 0.5 mL of either 0.9% NaCl or nitro-L-arginine (30 mg/kg). The severity of cytotoxic edema was evaluated based on changes in the water apparent diffusion coefficient (ADC) derived from diffusion-weighted images. The size of the area affected by ischemia was evaluated 3 hours after occlusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS The percentage decrease of ADC in the striatum of rats pretreated with nitro-L-arginine was significantly smaller (P < .05) than in the control group at 30 minutes and 1 and 2 hours of ischemia. The ADC in the injured cortex of nitro-L-arginine-treated rats did not differ significantly from the ADC value measured in the contralateral cortex until 3 hours after the occlusion. However, at 3 hours of ischemia the percentage decrease of ADC in both the striatum and the cortex of either group of rats was similar. This transient attenuation of ADC drop during ischemia after nitro-L-arginine pretreatment occurred concurrently with a transient improvement of blood supply to the ischemic regions. The percentage of hemispheric area with abnormal TTC staining after 3 hours of ischemia did not differ between control and nitro-L-arginine-treated rats. CONCLUSIONS Nitro-L-arginine delays the development of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood supply to the ischemia tissues.

Diffusion-weighted magnetic resonance imaging during brief focal cerebral ischemia and early reperfusion: Evolution of delayed infarction in rats

The purpose of this study was to ascertain if the signal intensity ratio and the lesion area determined by diffusion-weighted magnetic resonance imaging during brief focal ischemia and early reperfusion predict outcome determined by diffusion-weighted magnetic resonance imaging and T2-magnetic resonance imaging at 24 h. Seventeen rats were imaged before and during 30 min of endovascular middle cerebral artery occlusion and at 15 min, and 23.5 h after the onset of reperfusion. Both hemisphere and basal ganglia signal intensity ratio increased significantly from baseline during ischemia, decreased significantly from ischemic levels during early reperfusion, and increased again at 24 h. However, signal intensity ratio during ischemia or after 45 min of reperfusion did not correlate statistically with diffusion-weighted-signal intensity ratio at 24 h. Both hemisphere signal intensity ratio and basal ganglia signal intensity ratio at 15 min of reperfusion correlated, but only moderately, with diffusion-weighted-signal intensity ratio at 24 h (r = 0.52, p < or = 0.05). Although lesion areas during ischemia were comparable to those observed at 24 h, lesion areas at both 15 and 45 min of reperfusion were significantly smaller than those observed during ischemia and at 24 hr. Thus, sequential imagining demonstrated partial resolution and delayed recurrence of magnetic resonance-defined ischemic lesions during reperfusion after brief focal ischemia.

Multislice Measurement of First-Pass Transit of Gadobenate Dimeglumine in Normal and Ischemic Myocardium in Dogs

RATIONALE AND OBJECTIVES We monitored the differences in the first passage of gadobenate dimeglumine through normal and ischemic myocardium with left anterior descending (LAD) coronary artery occlusion in dogs. METHODS Dynamic multislice images of the heart were taken on a 1.5-T magnetic resonance (MR) imager. In six normal dogs, inversion recovery (IR)-prepared fast gradient-recalled echo (GRE) images were acquired at five doses of gadobenate dimeglumine (0.005-0.1 mmol/kg). First passage of the contrast medium through normal and acutely ischemic myocardium were monitored in seven dogs subjected to LAD coronary artery occlusion. RESULTS IR-prepared GRE images showed a dose-dependent increase in the signal intensity (SI) of the myocardium. In dogs with LAD coronary artery occlusion, there was a significant increase in the SI of normal myocardium (p < .01) than in ischemic myocardium after injection of 0.025 mmol/kg gadobenate dimeglumine. CONCLUSION The first-pass dynamics of gadobenate dimeglumine through normal and ischemic myocardium can be monitored with a multislice acquisition using a clinical MR imager and differentiated between normal and ischemic myocardium in dogs.