Abstract for presentation at The Australian and New Zealand Association of Neurologists Annual Scientific Meeting 2007

Purpose: Human [¹⁸F]FMISO-PET studies have demonstrated binding of FMISO with timing and distribution consistent with ischemic penumbra (the threatened but potentially salvageable tissue soon after stroke). A drawback of some penumbral imaging methods has been that mildly ischaemic tissue not at-risk of infarction (‘oligaemic’ tissue), or already irreversibly injured tissue (infarct core) is identified as penumbra. We conducted experiments to determine whether FMISO binds only tissue at risk of infarction.
Methods: A rat middle cerebral artery occlusion (MCAo) model was used. [³H]FMISO autoradiography was performed 24 hours after onset of MCAo, enabling correlation of histological outcome from the same tissue sections. [³H]FMISO was administered immediately post-MCAo in rats subject to 2 hour temporary MCAo. Autoradiographs and corresponding histological sections were overlayed to determine whether any FMISO-bound tissue was salvageable by reperfusion. Comparison cohorts with permanent MCAo and 24 hour or 6 day survival were used to determine final infarct size in the absence of reperfusion. To determine whether irreversibly injured tissues exhibit FMISO binding, tracer was administered 4-6 hours post-onset of 24 hour permanent MCAo (n=9). Striatal regions (infarct core) of autoradiographs and histology were examined.
Results: In the 2 hour temporary MCAo animals, the FMISO-bound volume was significantly greater than infarct volume (P<0.05, Table), but was not different to the infarct volumes in the permanent occlusion animals (24 hour or 6 day survival, Table). All animals with tracer administration 4-6 hours post MCAo demonstrated avid [³H]FMISO binding within striatum, corresponding to areas of greatest histological injury (Figure – representative autoradiograph + histology, red outline = area of FMISO binding above threshold).
Conclusions: These experiments demonstrate that FMISO binding occurs in ischaemic penumbra without significant binding in mildly ischaemic unthreatened (‘oligaemic’) tissue. However, avid binding was demonstrated in infarct core relatively early in stroke evolution.