Intracerebral hemorrhage (ICH), bleeding into the brain from a ruptured blood vessel, remains the most devastating stroke subtype, with 30-day mortality approaching 40% and severe functional impairments in the majority of survivors. The amount of blood that exits the ruptured vessel is the most powerful determinant of outcome in ICH, and while there are currently no proven treatments for acute ICH, the observation that continued bleeding and hematoma growth commonly occur points to an inviting therapeutic target. Two interventions (hemostatic and antihypertensive therapy) appear to slow hematoma growth, but this reduced expansion has thus far failed to translate into clinical benefit in clinical trials. These observations underscore the importance of clarifying the relationship between hematoma expansion and clinical outcome. Motivating the current proposal is the idea that improved predictive markers and biological characterization of hematoma growth will lead to efficient, personalized selection of optimal therapy. The goal of this approach is to target treatment to patients at highest risk for expansion and likeliest to respond to a specific therapy. We focus on two neuroimaging markers characterized by our group and others: 1) pooling of contrast or """"""""spot sign"""""""" on contrast CT angiography (CTA), a widely used extension of the standard emergency head CT;and 2) demonstration of cerebral microbleeds (CMB) on sensitive T2*-weighted MRI sequences, also part of the routine diagnostic evaluation of acute ICH. Accumulating evidence strongly supports CTA spot sign findings as powerful predictors of likelihood of expansion. Data from MRI imaging, though less definitive, also implicate CMB as markers of microvascular structure and associated risk of hematoma growth. As these two methods detect distinct aspects of ICH pathogenesis, our expectation is that they will provide complementary biological and predictive information regarding risk of expansion. Our overall goal is to apply CTA and MRI to identify patients at highest risk for hematoma expansion. Partnering with the Antihypertensive Treatment in Acute Cerebral Hemorrhage-2 (ATACH-2) trial, we will determine whether CTA and MRI can identify patients at high risk for hematoma growth and whether these imaging techniques can select patients more likely to benefit from early, intensive antihypertensive treatment. Our proposal takes advantage of three specific factors: 1) the tremendous leverage obtained from building on the wealth of data to be collected in ATACH-2, 2) the widespread use of CTA and T2*-weighted MRI by tertiary stroke centers in the clinical evaluation of ICH (thus necessitating no separate consent process for enrollment in our substudy), and 3) our research group's widely recognized expertise in the interpretation of both of these techniques. Successful completion of the proposed studies will be a major step towards optimizing the application of current and future approaches to hematoma growth and establishing tangible improvements in ICH outcome.

Public Health Relevance

Intracerebral hemorrhage (ICH), bleeding into the brain from a ruptured blood vessel, is the deadliest stroke subtype and there are currently no proven effective treatments for patients with ICH. The Antihypertensive Treatment in Acute Cerebral Hemorrhage-2 (ATACH-2) trial will determine whether urgently administered aggressive blood pressure control can improve ICH outcome. The proposed studies will investigate whether routinely obtained brain imaging studies can select the patients most likely to benefit from this intervention.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Janis, Scott
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Morotti, Andrea; Dowlatshahi, Dar; Boulouis, Gregoire et al. (2018) Predicting Intracerebral Hemorrhage Expansion With Noncontrast Computed Tomography: The BAT Score. Stroke 49:1163-1169
Akhter, Murtaza; Morotti, Andrea; Cohen, Abigail Sara et al. (2018) Timing of INR reversal using fresh-frozen plasma in warfarin-associated intracerebral hemorrhage. Intern Emerg Med 13:557-565
Prins, Bram P; Mead, Timothy J; Brody, Jennifer A et al. (2018) Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6. Genome Biol 19:87
Crawford, Katherine M; Gallego-Fabrega, Cristina; Kourkoulis, Christina et al. (2018) Cerebrovascular Disease Knowledge Portal: An Open-Access Data Resource to Accelerate Genomic Discoveries in Stroke. Stroke 49:470-475
Arsava, E Murat; Helenius, Johanna; Avery, Ross et al. (2017) Assessment of the Predictive Validity of Etiologic Stroke Classification. JAMA Neurol 74:419-426
Morotti, Andrea; Brouwers, H Bart; Romero, Javier M et al. (2017) Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage: A Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol 74:950-960
Morotti, Andrea; Romero, Javier M; Jessel, Michael J et al. (2017) Phantom-based standardization of CT angiography images for spot sign detection. Neuroradiology 59:839-844
Marini, Sandro; Morotti, Andrea; Ayres, Alison M et al. (2017) Sex differences in intracerebral hemorrhage expansion and mortality. J Neurol Sci 379:112-116
Grunwald, Zachary; Beslow, Lauren A; Urday, Sebastian et al. (2017) Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage. Neurocrit Care 26:205-212
Morotti, Andrea; Boulouis, Gregoire; Romero, Javier M et al. (2017) Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion. Neurology 89:548-554

Showing the most recent 10 out of 45 publications