Grant: Project Grant

There is no effective treatment for bleeding into the brain or ICH. While we cannot do anything about the initial ICH, expansion of a bleed is the most important cause of bad outcome in ICH. We first described the Spot Sign which, when seen in ICH, strongly predicts expansion. We developed clinical trials (that are ongoing) selecting patients for treatment with drugs that stop bleeding based on the presence or absence of the Spot sign. There is evidence now however to suggest that this approach is flawed as the Spot sign represents varying rates of ICH expansion rather than an all-or-none situation. In other words, some Spot positive bleeding may be so quick that no medical treatment will be effective while others so slow that no treatment is needed because no meaningful expansion will occur. The problem is that current studies will not tell us what rates of bleeding are responsive to existing medicines and will likely fail because we did not consider the rate of bleeding. We have therefore developed a unique animal model that most closely mimics the Spot positive bleeding that occurs in humans. By aiming ultrasound beams from outside the head to specific brain regions we are able to damage the walls of small vessels causing them to rupture. By controlling the power of the ultrasound delivered we can adjust the rate of bleeding by targeting different vessel sizes. We propose using this model to test existing (medicines) and new (new medicines, using ultrasound to stop bleeding and surgical) ways to minimize expansion of bleeds based on the rate of bleeding associated with Spot positive bleeds. Once the ranges of bleeding rates responsive to our proposed medicines and novel treatments are established we can test these in humans using existing imaging sequences that measure rates of bleeding. By selecting patients based on these measures we can tailor treatment to the particular rate of bleeding ensuring better outcomes, less dependency and lower cost to society