Multimodal optical imaging investigation of neuronal, metabolic and vascular correlates of aging

随着年龄的增长，认知功能的恶化对加拿大人的生活产生了重大的个人、社会和经济后果，特别是在目前的人口背景下。认知能力下降的原因和机制尚不清楚，可能是多方面的（神经、代谢和血管）。有证据表明，健康的衰老和疾病对基线血流量和血管顺应性有影响，这表明血液动力学测量与调查和最终诊断与年龄相关的疾病有关。

Deteriorating cognitive function with aging has significant individual, social and economic consequences on the lives of Canadians, particularly given the current demographic context. The causes and mechanisms of cognitive decline remain unclear and could be manifold (neural, metabolic as well as vascular). There is evidence that healthy aging and disease have effects on baseline blood flow as well as vascular compliance, suggesting the relevance of hemodynamic measurements for investigating and eventually diagnosing age-related conditions. While traditional studies with (functional) magnetic resonance imaging provide high resolution imaging of the brain and its vasculature, no diagnostic tool exists that can inform a clinician on whether someone will develop a neurodegenerative disease. The interpretation of the BOLD signal, vastly used in brain mapping, is complicated as it results from combined changes in blood flow, volume and oxygenation. Furthermore, the hemodynamic baseline state (e.g., blood flow and metabolic rate at rest) has been shown to affect functional data, but is typically not measured in functional imaging studies. In heterogeneous populations such as the elderly, the influence of baseline physiology on functional measurements, changes in the structure of the vascular network and its density in the brain are a cause of inter-subject variability in data. These confounds of hemodynamic measurements limit the applicability of imaging techniques as eventual diagnosis tools. Towards the goal of elucidating the mechanisms of aging and its relation with changes in the hemodynamic response, this projects proposes to first develop a combination of complementary optical imaging techniques including: intrinsic optical imaging, speckle flow imaging, Doppler optical coherence tomography and two photon microscopy. Then, biophysical models previously proposed discriminate the contributions of metabolic and vascular processes in the measured hemodynamic response will be validated against microscopic data in animal models of aging and hypertension.