[Thesis] Modeling and Assessment of Cerebrovascular Regulation of Cerebral Blood Flow

Computational models designed to continuously evaluate the state of regulation of cerebral blood flow (CBF) in the clinical setting and to provide a further understanding of the electrical interactions between smooth muscle cells and endothelium cells during intact and impaired regulation are needed. To address the clinical need for a method to evaluate the state of regulation of CBF, a novel two-step modeling method of cerebrovascular pressure transmission, the dynamic relationship between arterial blood pressure (ABP) and intensive care intracranial pressure (ICP), was developed. Each model is constructed from these pressure recordings over a brief period of time in which the cerebrovascular pressure transmission is assumed to be linear and time-invariant. Results of laboratory and clinical studies provide support for the potential use of the proposed methodology as a clinical tool to continuously assess changes in cerebrovascular resistance, cerebral blood flow and the state of cerebrovascular autoregulation. Specifically, changes in model-derived cerebrovascular resistance and cerebral blood flow followed changes in physiological and pathological conditions. To address the need for a further understanding of the electrical communications between smooth muscle and endothelial cells during intact and impaired regulation of cerebral blood flow, a descriptive model based on experimental observations was developed. This descriptive model is based on an assumed electrical network that describes changes in electrical activity between micro-units of aggregate arteriolar smooth muscle cells and endothelial cells. The model describes changes in underlying electrical activity associated with the dynamics of pressure-induced vasoconstriction during intact regulation and vasodilation during impaired regulation. Chapter 1. Introduction Chapter 2. Background 2.1 Monroe-Kellie doctrine and intracranial pressure 2.2 Cerebrovascular autoregulation 2.3 Traumatic Brain Injury (TBI) 2.4 Plateau Wave 2.5 Intractable Intracranial Hypertension Chapter 3. Laboratory Preparations and Data recording 3.1 Animal Preparations 3.2 Closed Cranial Window Preparation 3.3 Data Acquisition 3.4 Video micrometric Measurements Chapter 4. Two Step Modeling Method 4.1 Previous Studies of Cerebrovascular Pressure Transmission 4.2 First Step of Computational Modeling of Cerebrovascular Pressure Transmission 4.3 Second Step of Computational Modeling of Cerebrovascular Pressure Transmission 4.4 Pial Arteriolar Diameter Measurement and Resistance Computation 4.5 Summary Chapter 5. Assessment of Cerebrovascular Resistance with a model of cerebrovascular pressure transmission Chapter 6. Influence of Hypercapnic Vasodilation on Cerebrovascular Autoregulation and Pial Arteriolar Bed Resistance in Piglets Chapter 7. Assessment of Cerebrovascular Resistance with Model of Cerebrovascular Pressure Transmission Chapter 8. Cerebrovascular Autoregulation: Functional Model Description of Electrical Coupling between Smooth Muscle Cell and Endothelial Cell Chapter 9. Conclusions References Appendix A A. 1. Component Abbreviation for Figure 4.3 Appendix B B.1. Flow Chart of Two Step Modeling Method B.2. Flow Chart of First Step of Modeling Method B.3. Flow Chart of Second Step of Modeling Method B.4. Flow Chart of Pial Arterial Diameter Measurement Appendix C C. 1. Two Step Modeling Method Algorithm C.2. First Step of Modeling Method Algorithm C.3. Second Step of Modeling Method Algorithm C.4. Diameter Measurement Algorithm Appendix D D.1. Copy of Institutional Review Board Approval (E03-233) D.2. Copy of Animal Research Protocol (Number 004)