The overall aim of this project is to test whether a new method for forcibly dilating severely constricted cerebral arteries will restore normal perfusion to distal tissues suffering hypoperfusion and at risk of ischemic injury. Laser-induced propagating """"""""pulsed-fluid waves,"""""""" recently discovered in our laboratories, are generated by very brief, low energy pulses of laser light within very small angiographic catheters and can physically dilate constricted intracranial arteries. Several unique properties of the laser/catheter system will be tested to demonstrate that """"""""pulsed-fluid wave"""""""" dilation in SAH patients are currently ongoing. Our proposed in vivo studies aim to optimize the adjustable parameters for holmium-laser induced pulsed-fluid wave dilation and to determine those parameters necessary to ensure that the reversal of constriction is sufficiently long-lasting to be of clinical value. In vitro studies are proposed to test our hypothesis that propagating pulsed-fluid waves will penetrate deep into cerebrovascular perfusion beds, areas inaccessible to direct balloon catheterization, to achieve more complete restoration of tissue perfusion. Other in vitro studies will test whether the mechanism of forced dilation involves the death of vascular smooth muscle cells, initiating processes of vascular remodeling, as assessed by studies of morphology and contractility. High spatial and temporal resolution """"""""functional CT"""""""" imaging (fCT) will be used to identify in our animal model those specific brain areas which exhibit perfusion deficits due to cerebral vasospasm after experimental-SAH. fCT mapping of the therapeutic response to pulse-fluid wave dilation will clarify the correlation between large vessel constriction and local cerebral perfusion; providing """"""""on-line"""""""" monitoring of the therapeutic response in future clinical trials.
