Human Intracerebral Hemorrhage: Impact of Hematoma Size, Hemolysis and Iron Overload on Edema and White Matter Survival by MRI

Project Abstract – There is currently no evidence for an established treatment paradigm for intracerebral hemorrhage (ICH). The most recent clinical trials on hematoma evacuation and iron chelator treatment have not shown a significant improvement in neurological function. No objective surrogate markers of disease severity currently exist to guide prognosis. MRI is inherently more informative about local tissue changes following hemorrhage in the brain tissue than CT. We have recently completed our first translational MRI study (R21 - NS099684) validating MRI based evaluation of iron overload in the brain tissue following ICH in 20 patients. We have also demonstrated in another completed R21 (NS-104663) that proportional erythrolysis within hematoma can be quantified reliably on MRI. Its influence on iron overload to the surrounding tissue, perihematomal edema and white matter (WM) survival within the hematoma can be robustly recorded in acute and subacute phases (7 – 10 days) and chronic phase (up to 6 month). In addition, our preliminary data shows that the above markers have a correlation with surviving WM within hematoma and the perihematomal region. The proposed study aims to track natural history of ICH in terms of variations in above mentioned multiple MRI markers, from acute (7-10 days) to the chronic phase (up to 6 months). It will particularly address the importance of early erythrolysis on perihematomal iron overload and acute white matter injury (day 7-10); the impact of hematomal and perihematomal iron overload on white matter tract survival (days 7-10); and the effect of iron overload on white matter tract recovery and brain atrophy after ICH (day 180). This study is important because this translational work will establish MRI markers of iron mediated neurotoxicity and thus better inform future trials, objectively evaluating newer treatment strategies including both image-guided mechanical hematoma evacuation as well as pharmacological therapy for ICH.