30 MATRIX METALLOPROTEINASES, THEIR ENDOGENOUS INHIBITOR AND APPARENT DIFFUSION COEFFICIENT REDUCTION ON MAGNETIC RESONANCE IMAGING: A COMPARISON OF HUMAN SERUM AND RADIOGRAPHIC MARKERS IN ACUTE ISCHEMIC STROKE

BackgroundHuman matrix metalloproteinase-9 (MMP-9) has been studied as a biomarker in acute stroke injury and as a potential target of therapy. MMP-9 is a zinc-dependent endopeptidase that participates in extracellular matrix remodeling, and is a major mediator of t-PA-related adverse outcome and blood-brain-barrier (BBB) disruption in animal models of focal ischemia and spontaneous intracerebral hemorrhage (ICH). In vitro findings also suggest that exogenous MMP-9 inhibition may improve cerebral ischemic tissue outcome. Reduction in the apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) has been utilized as a quantitative radiologic marker of acute cerebral ischemic injury. Using non-invasive quantitative MRI techniques, we wish to validate MMP as a potential surrogate marker of cerebral injury in humans, by investigating the relationship between MMP-9, its endogenous inhibitor TIMP-1, and the extent of cerebral ischemic injury as measured by early ADC reduction.MethodIn 36 patients with acute ischemic stroke, plasma levels of MMP-9 and TIMP-1 were measured at mean 6 hr post stroke. DWI was obtained at mean 8 hr post stroke. Within each lesion, we calculated the percent of voxels showing ADC reduction at or below each of 8 incremental thresholds, at intervals of 90 × 10-6 mm2/s, from 185 × 10-6 to 825 × 10-6 mm2/s.ResultAcute TIMP-1 level was inversely correlated to the percent of voxels with ADC reduction at or below the lowest threshold, 185 × 10-6 mm2/s (r = -0.41, p