Changes in Diffusion-Weighted Images During Transient Cerebral Hypoxia-Ischemia Correlate with Reductions in Extracellular Space using Electron microscopic and Impedance Techniques.
Background: Experimental animal and clinical studies indicate that diffusion-weighted imaging detects early ischemic changes which are assumed to reflect reductions in extracellular space and cellular edema. In the present study, we investigate this directly by measuring intensity changes in diffusion-weighted images and alterations in extracellular space using electron microscopic and impedance techniques during and after transient cerebral hypoxia/ischemia in rats. Methods: The right carotid artery was isolated surgically (sham control) or occluded with subsequent exposure to 8% oxygen for 2 hours in 31 one-week old Wistar rats. Diffusion-weighted images were obtained prior to, during, at 1 or 24 hours post hypoxia/ischemia. Animals were decapitated after either the sham procedure, during hypoxia/ischemia or at 1 or 24 hours post hypoxia/ischemia. The rat brain was flash frozen and processed for electron microscopic quantitation of extracellular space immediately after imaging. Extracellular space was also assessed by recording impedance changes prior to, during and for 1 hour post hypoxia/ischemia. Results: Intensity on diffusion-weighted images increased 78% ipsilaterally during hypoxia/ischemia, substantially recovered at 1 hour post hypoxia/ischemia, and increased 49% again at 24 hours post hypoxia/ischemia. Stereologic analysis of extracellular space from electron micrographs of the cortex in controls was 51 ± 6% of total space. This decreased to 3 ± 1% during hypoxia/ischemia, returned to 30 ± 21% at 1 hour post hypoxia/ischemia and was 43 ± 7% at 24 hours post hypoxia/ischemia. Impedance measurements within the ischemic cortex demonstrated that extracellular space decreased 40% during hypoxia/ischemia and recovered to control levels at 1 hour post hypoxia/ischemia. Conclusions: Increased intensity on diffusion-weighted images corresponds well to a reduction in extracellular space.