Translational Neuroimaging of Cerebral Perfusion after Acute Ischemic Stroke

Abstract

An ischemic stroke occurs due to a blockage in the blood supply to the brain, often caused by a blood clot. This disruption leads to permanent brain damage and can result in a lasting disability or death. Medical imaging techniques such as MRI and CT are used to characterize this damage and the blood flow in the brain, which is crucial for patient triage. Treatments to clear the blocked blood vessels (“recanalization therapy”) can restore blood flow, but clinical effectiveness is not guaranteed. Many patients remain dependent on care or die within months after treatment, despite successful recanalization. The failure of treatments is a significant clinical problem with unclear causes. There are indications that blood flow in the ischemic brain tissue after recanalization is incomplete, which could contribute to treatment failure. This dissertation aims to clarify the cause-and-effect relationships of treatment failure, with a special focus on the role of cerebral reperfusion after treatment. The central hypothesis is that blood flow in the brain immediately after treatment plays an important role in disease outcome. Since this is difficult to investigate in patient populations, much of the information was gathered through preclinical animal models using translational imaging techniques, primarily MRI. An initial literature review describes various abnormalities in brain blood flow after a stroke, including both insufficient and excessive blood flow. Both abnormalities can affect the treatment efficacy. Subsequent chapters present experimental results suggesting that blood flow in the brain after recanalization is not always deficient. However, when combined with conditions such as hypertension, incomplete blood flow can indeed occur, leading to worse disease outcomes. There are also indications that excessive blood flow under certain circumstances can be beneficial or harmless. Additional chapters establish the effects of different types of anesthesia on treatment outcomes. Additionally, blood flow and inflammation are characterized in the brain after ischemia using new experimental techniques, ultrafast ultrasound and molecular MRI respectively. This dissertation provides new insights into brain blood flow after a stroke and its associations with disease progression. These insights may serve as starting points for future research into the causes, consequences, and possible treatments of the (in)effectiveness of recanalization therapies in both humans and animals, using translational imaging techniques.