Grant: Research Tools and Instruments

<p>The brain does not store energy but maintains a very high metabolic rate. Therefore, the brain requires about 20% of the total cardiac output on a continuous basis leading to a highly regulated vascular system. Yet, our knowledge of how the brain controls its blood flow during rapid changes in perfusion pressure (e.g. standing upright), or during arousal stimuli that engage neurogenic mechanisms, remain poorly understood because the skull limits direct access to the blood vessels. As a result, indirect measures often are used such as blood flow velocity in the large subcortical vessels (assuming these reflect real blood flow), and measures of blood pressure in the finger to represent vascular pressure in the brain. Although inadequate, few options exist. More fundamentally, conceptual models of cerebrovascular control rely on steady state concepts such as vascular resistance which ignores the oscillatory nature of blood flow - blood pressure relationships. Quantification of oscillatory flow dynamics provides information about the vascular wall such as vascular compliance and viscoelasticity. These properties, not yet reported in the intact human brain, require concurrent measures of blood flow and blood pressure waveforms at strategic points in the intact cerebrovascular bed. The equipment requested in this proposal will, for the first time, enable the concurrent quantification of intravascular blood flow and pressure waveforms at various segments of the intact human brain (common carotid, carotid sinus, internal carotid, Circle of Willis, cerebral arteries) with both high temporal resolution and fidelity. This ComboMap device incorporates a catheter-based system with Doppler and pressure sensors at the tip of a microwire that provides analog data ouputs (Lifemed Group). A dedicated analog-to-digital data acquisition system (Powerlab Adinstruments) will enable collection and analysis of the data. From these data, the first lumped Windkessel model of the human cerebral vascular properties will be developed based on human data, validated in a phantom of the cerebrovascular bed, applied to the study of dynamic properties involved in human cerebrovascular control, and used in support of new tool development that aims to provide non-invasive indices of volumetric blood flow based on validated assumptions of velocity - pressure relationships. This equipment will lead to a new interdisciplinary collaborative initiative among three disciplines, namely, Physiology, Physics and Engineering. Consequently, this new tool will introduce new interdisciplinary graduate training experiences for model development, as well as in application studies, producing new knowledge about mechanisms regulating dynamic properties of the brain's blood flow and its control in intact humans.</p>