Functionalized nanoparticles for real time imaging of cerebral lesions

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Stroke victims commonly suffer micro-ischemic lesions of the brain that initially remain unnoticed due to their small size. In the long term, however, they tend to trigger irreversible neurodegenerative changes accompanied by debilitating complications for which no cure has been found. We propose here to develop new real time non-invasive imaging protocols using luminescent nanoparticles or X-ray computed tomography (CT) contrast agents. Our approach is unique in as much as it relies on the synergy of (i) materials nanoscience for the design and synthesis of imaging agents, (ii) mechanistic pharmacology for the deployment of imaging and pre-clinical studies and (iii) state-of-the-art medical imaging technology, which will be provided by instrumentation designed and commercialized by the Canadian-based company ART Advanced Research Technologies Inc. The overall objectives are: 1. to develop and test novel near IR emitting quantum dots and X-Ray tomography contrast agents suitable for real time, non-invasive 1 imaging; 2. to use these imaging tools to assess the extent of ischemic lesions in rodent stroke models; and 3. to test the effectiveness of new intranasal formulations of either NAD+ (Nicotinamide adenine dinucleotide), a drug in clinical use clinically, and of a drug "cocktail", composed of minocycline, riluzole and nimodipine, used in pre-clinical investigations. While the research proposed is aimed towards preclinical screening methods for drugs in the treatment of ischemic lesions, the imaging devices and agents developed will be widely applicable in pre-clinical research and benefit the Canadian health community by providing fast, sensitive, and reliable methods in drug development and diagnostics