Project Summary/Abstract Penumbral salvage is a central dogma of acute stroke care. Radiological characterization of the penumbra has transformed acute ischemic stroke care by carefully selecting patients who may benefit from acute intervention. No such innovation has taken place in intracerebral hemorrhage (ICH). Our central hypothesis is that there is a “mechanical penumbra” surrounding the hemorrhage - an area that is mechanically compressed and at risk of becoming irreversibly damaged – but still salvageable if the compression is relieved in a timely manner. Randomized clinical trials of cerebral hematoma evacuation have not consistently shown a benefit. A potential explanation for these results is that we have failed to radiologically select patients who may still have salvageable tissue and are most likely to benefit from hematoma evacuation. Most ICHs occur in the putamen and thalamus, which border the internal capsule (IC). The internal capsule consists of the long axons of the corticospinal tract connecting the cortex with the spinal cord. Structural damage to the IC is the major determinant of functional outcomes after ICH. Preserving the structural integrity of the IC should therefore be the therapeutic goal. Diffusion-tensor imaging (DTI) is a magnetic resonance-based imaging technique which allows for the structural assessment of axons in the white matter, such as the IC. DTI detected damage to the IC highly correlates with long-term functional outcome after ICH. We hypothesize that this mechanical penumbra in ICH can be evaluated using DTI imaging (using fractional anisotropy (FA) values, and other measures). Our preliminary data support the feasibility of using DTI imaging and the ability to identify spatial and temporal shifts of FA values at baseline and in the early hours after ICH. Identifying mechanical penumbra may facilitate the selection of patients for surgical intervention in future clinical trials. In this study, we propose serial MR DTI imaging at the time of ICH presentation (< 12h from symptom onset), at 24h, and at 10-14 days after injury in 24 patients. We will analyze DTI sequences for radiological markers of permanent injury. The IC will be segmented into three zones emanating from the hematoma to determine if there is a gradient of DTI measures (including FA values). We hypothesize that axons closest to the hemorrhage have the lowest (damaged axons) and those furthest away from the hemorrhage have the highest (preserved axons) FA values. Demonstrating such a gradient of FA values around the ICH suggests the presence of axons with variable degrees of injury, some of which may still be salvageable. (Aim 1) We will then investigate the temporal evolution of these axons and correlate the impact of this evolution on functional recovery at 3-month follow-up (Aim 2). We hypothesize that an improved DTI measures is associated with good functional outcomes whereas a deterioration of FA values over time is associated with ...