The pathophysiology of cerebral arteriovenous malformations (AVMs) is incompletely understood, and hemodynamic changes associated with obliteration of a high-flow shunt by surgery or embolization are considered important in evaluating the risk of intervention. Investigation of this disease process and its treatment provides an unprecedented opportunity to study the effect of drastic hemodynamic changes in the human cerebral circulation and to clarify the physiology of collateral blood flow and autoregulatory phenomena. It is the aim of this study to document rigorously the changes in cerebral hemodynamics during the course of intervention by direct measurement of cerebral perfusion pressure, blood flow and blood volume, using 133Xe regional Cerebral Blood Flow (133Xe CBF), transcranial Doppler ultrasound (TCD), and Single-Photon Emission Computerized Tomography (SPECT). We will also quantify cerebrovascular regulation by manipulation of arterial carbon dioxide tension (CO2) and blood pressure. We have constructed a detailed hypothetical model of AVM hemodynamics to serve as a framework for classification for AVMs. This model treats the hemodynamic consequences of AVMs as a subset of occlusive cerebrovascular disease and low-grade chronic ischemia, which will provide a consensual model for analysis and an opportunity to generalize observations to other conditions. One hundred fifty-two AVM patients over a four-year period will participate in the study. Patients will be assessed before and after treatment using standard imaging techniques, including computerized tomography, magnetic resonance imaging, and cerebral angiography, as well as TCD. In the highest risk patients, SPECT procedures will provide transverse images of tissue perfusion (with 123I- IMP) and cerebral blood volume (with 99m Tc-RBCs) before and after AVM treatment. During treatment, all patients will have 133Xe CBF and in situ AVM vascular pressure measured immediately before and after surgical obliteration of therapeutic embolization of the AVM. Hemodynamic changes will be correlated with preoperative risk (derived from clinical and imaging data) and postoperative outcome. In addition, intraoperative cerebral hemodynamics will be studied in a control group of 48 patients. It is expected that a better understanding of pathophysiology of these complex lesions gained by this study can be used to better formulate treatment plans, design strategies to prevent adverse outcomes and more rationally manage those that occur. Most importantly, a more rigorous understanding of the determination of the relationships between flow, pressure and resistance in the human cerebral circulation will have implications for all life-threatening vascular disorders of the central nervous system.
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