Grant: Discovery Grants Program - Individual

We are building non-invasive imaging methods that can monitor changes in the activity and structure of the brain related to the body's immune response to toxins, infections, and injury (also known as neuroinflammation). Key features of neuroinflammation include: 1) activation of resident neuroinflammatory cells (known as microglia), 2) breakdown of the barrier that protects the brain from toxins in the blood (known as the blood-brain barrier or BBB) 3) infiltration of peripheral white blood cells, and 4) consequences of neuroinflammation, including changes in brain chemistry and structure. Activated microglia can be beneficial, maintaining healthy brain cells and removing unwanted invaders, but prolonged neuroinflammation can diminish brain health, often preceding brain tissue damage and cognitive symptoms in a wide variety of disorders, including autoimmune diseases, psychiatric disorders, stroke, and dementia. Because of this, early detection and treatment of neuroinflammation would be beneficial for the long-term brain health of Canadians. In order to get a more complete assessment of neuroinflammation and its consequences, approaches that combine information from multiple non-invasive imaging methods are needed. This can be accomplished with two complementary imaging technologies: magnetic resonance imaging (MRI) and positron emission tomography (PET). With MRI, we will detect neuroinflammatory cells with measurements sensitive to different tissue features, neurotransmitter chemicals that get overexpressed during neuroinflammation, and breakdown of the BBB. With PET, we can inject minute amounts of radiolabeled drugs that directly target activated microglia and synaptic density (a marker of brain health). The primary objective of this NSERC Discovery Grant will be to develop and validate methods that combine PET and MRI measures of neuroinflammation and its consequences. These methods will be validated using male and female preclinical models of neuroinflammation and gold standard tissue analysis, with the goal of developing a comprehensive imaging platform for assessing neuroinflammation using simultaneous PET/MRI. This research program will lay the groundwork for 1) improved understanding of the brain in health and disease and 2) testing therapeutic interventions that may slow or halt disease progression. Importantly, there is a clear path between the proposed imaging research program and future studies in human brain disease using the clinical PET/MRI at the Lawson Health Research Institute. A holistic neuroinflammation imaging platform will lead to more successful diagnostic exams and treatments in patients with brain disease, reducing the need for repeat visits and improving diagnostic efficacy. This, in turn, will have a substantial economic and societal benefit for all Canadians.