When a person first exhibits signs of having a stroke, the timing of treatment is critical to restore blood flow to the brain and support recovery. In addition to studying and implementing ways to treat patients faster, investigators have been studying how to make predicting and treating stroke more precise. A new study in the journal Stroke introduces a concept of brain imaging known as blood-brain core imaging, or “leaky core,” that could potentially accelerate this progress and transform the way that many strokes are treated.
“We are constantly advancing our stroke prevention strategies, our acute stroke treatments, our post-stroke management and our stroke rehabilitation options,” says Richard Leigh, M.D., the first study author, a neurologist and the director of the Johns Hopkins Neuro Vascular Brain Imaging Laboratory. “It is likely that imaging the blood-brain barrier, which is itself a marker of brain health, can help us improve all of these interventions.”
After reviewing 291 post-stroke brain scans, the researchers, including scientists from France, the U.S. and Spain, could see and study areas affected by blood-brain barrier disruption. Also known as a leaky core, blood-brain barrier disruption — where the walls of blood vessels in the brain become more permeable or flexible and can start to break down or leak — is believed to signal underlying injury and inflammation. This index has also served as a marker for increased risk of hemorrhage or bleeding after an ischemic stroke (which accounts for most cases and results from a blocked or narrowed blood vessel in the brain).
Through this imaging study, which is supported in part by the National Institutes of Health (NIH), investigators found that for every 1% increase in blood-brain barrier disruption, the odds of a person having a poor outcome, such as requiring help with care or experiencing severe disability or death, three months after an ischemic stroke increased by 16%.
“The importance of the blood-brain barrier has been known, but it is often overlooked because we didn’t have a good way to take pictures of it,” says Leigh. “One of the reasons this research is taking off is because it uses information from a sequence that is already being collected as part of brain scans.”
This algorithm, which calculates insights about blood vessel leakage in affected areas of the brain, is generated from existing MRI scans taken after a person experiences a stroke. Currently, MRI enables physicians to assess damaged areas and create treatment plans. This includes creating strategies to preserve areas of the brain that can be saved while mitigating risks for complications like bleeding. The “leaky core” imaging, Leigh explains, could enable researchers to “open up” views of affected areas to tailor these plans.
“We want to be as accurate as we can to deliver the best care to patients,” says Leigh. “This imaging gives us another piece of data to assess what’s going on in the brain.”
For example, if a person has signs of blood vessel permeability or leakage, they may still be eligible for certain interventions, such as a thrombectomy (a procedure that mechanically removes blood clots from the brain). However, to offset risks for bleeding, a physician may decide to not start treatment with blood thinners, or may opt out of using blood clot-dissolving medication following the procedure. Alternatively, the leaky core imaging may identify patients who, based on conventional imaging, would be perceived to be unlikely to benefit from treatment, but based on this new imaging (demonstrating that their blood vessels in the affected area are intact), could receive treatment. This could allow for expansion of treatments to patients who in the past may have gone untreated.
This approach opens up the possibility for patients to safely receive blood thinners and clot-dissolving treatments, which could potentially bolster recovery.
Leigh notes that there are also other uses for the imaging. “Ultimately, the blood-brain barrier is a target,” he says. Outside of studying new therapies and treatments, this leaky core imaging could inform the development of targeted, and therefore more efficient, clinical trials. By identifying treatments that work, or don’t, to preserve the blood-brain barrier, new therapies could be identified faster and with fewer costs and resources. Another way the blood-brain barrier imaging could be used is to help monitor adults who have had a stroke and have increased risks for post-stroke complications, such as experiencing a second stroke or dementia. This imaging, combined with ongoing research to identify additional markers for cognitive health, could potentially provide neurologists and care teams with insight to intervene at earlier stages. “Stroke can be a devastating disease,” says Leigh. “Yet with advances in technology and precision medicine approaches, curing stroke is a possibility.”
Additional study authors include Nefeli Valyraki, Nae-Yuh Wang, Manar Abomulay, Adrien ter Schiphorst, Adrián Valls Carbo, Maria Hernández-Pérez, Frédérique Charbonneau, Caroline Arquizan, Anne Wacongne, Denis Sablot, Vincent Costalat, Canan Ozsancak, Clara Cohen, Marco Pasi, Grégoire Boulouis, Nicole Yuen, Jean-Philippe Desilles, Gregory W. Albers, Jean Marc Olivot and Pierre Seners. The study was funded by La Agence Nationale de la Recherche (ANR) (PRECISE-STROKE grant number ANR-23-CE17-0058), Methods to Evaluate Segmentation and Indexing Techniques (SAVE BRAIN-AAP-2023-MSDR-341091), the NIH (R01NS123386), the American Heart Association (23IPA1043237) and la Société Française de NeuroVasculaire (SFNV). Leigh discloses a patent issued for System and method for blood-brain permeability imaging (US Patent US10076263B2).
