Introduction: The Levine model of hypoxic-ischemic encephalopathy(HIE) was investigated using dynamic interleaved diffusion MRI and perfusion weighted MRI, employing an intravascular iron containing blood pool contrast agent. Diffusion MRI yields maps of tissue apparent diffusion coefficient(ADC) which indicate the presence of cytotoxic edema. Perfusion MRI yields relative cerebral blood volume (CBV) information.

Methods: New Zealand White rabbits (8-14 days old, n=9) were anesthetized with halothane and one common carotid artery (CCA) was ligated. Variable FiO2 administration was by nitrogen dilution. MRI was performed using snapshot echo planar imaging (EPI). Interleaved T2 and diffusion weighted EPI images were acquired continuously during HIE. Iron Dextran was injected to sensitize T2-weighted images to changes in blood volume. Serial ADC and relative CBV maps were generated every 9 seconds. After contrast injection, animals (n=7) were exposed to 10% FiO2. Hypoxia was reversed when reduced ADC was observed over the entire ipsilateral hemisphere. Mean arterial blood pressure was measured continuously. Control animals (n=2) were not exposed to hypoxia.

Results: Immediately post-hypoxia there was globally increased CBV. In 2 animals diffusion abnormalities appeared soon after the onset of hypoxia then rapidly progressed to global ischemia. Animals then suffered cardiac arrest. In 5 animals, diffusion changes appeared focally and spread more slowly over the ipsilateral cortex. These changes rapidly reversed upon return to normoxia. Concurrent with the focal ADC drop, there was a localized CBV decrease in the same regions, which returned to baseline on normoxia. In control animals (n=2) there was no change in ADC or CBV.

Conclusions: Dynamic concurrent diffusion/CBV MRI is a sensitive means of serially monitoring the acute hemodynamic and metabolic related effects of HIE in vivo. The use of an iron contrast agent allows for frequent repeat measurements of CBV by MRI. In this model of HIE, focally decreased ADC and CBV changes showed similar temporal evolution and returned to at least baseline values post hypoxia.