Introduction: Annexin V is an endogenous protein which binds to phosphatydylserine that is selectively expressed on the surface of apoptotic cells. Apoptosis has been seen in neonatal rat models of hypoxic ischemic encephalopathy (HIE). Experimental HIE in neonatal rabbits results in areas of focally decreased apparent diffusion coefficient (ADC), indicating cytotoxic edema, primarily in ipsilateral cortical tissue. These areas of decreased ADC return to above baseline values post hypoxia. We have used radionuclide scanning (technetium labeled annexin V, Tc-AV) and MR diffusion imaging (ADC mapping) in the neonatal rabbit model to investigate possible apoptotic cell death associated with these reversible ADC changes.

Methods:Neonatal New Zealand White rabbits (n=7) were anesthetized with halothane, the right common carotid artery (CCA) was ligated and a catheter was placed into the left external jugular vein. Animals were scanned in a 2.0T Bruker/GE Omega MRI system. Variable FiO2 administration was by nitrogen dilution. Vital signs were continuously monitored. Dynamic multislice MRI scans were performed yielding ADC maps. Tc-AV (1mCi) was injected i.v. and brains were scanned using a gamma camera with a 1mm pinhole collimator.

Results: Animals subjected to hypoxia and CCA ligation (n=4) showed reversible ADC changes, but no blood brain barrier breakdown post hypoxia. There was marked uptake of Tc-AV detected in the brains of these animals. Focally increased Tc-AV and focally decreased ADC distribution appeared to be different. There were no areas of focally increased Tc-AV uptake in the brains of normal (n=1) and sham operated animals (n=2).

Conclusions: Brain Tc-AV uptake only occured in animals whch were subject to CCA ligation and hypoxia. Focally increased Tc-AV uptake, consistent with apoptotic injury, has been visualized in vivo using radionuclide scanning.