There is little doubt that disturbed hemodynamic forces play a role in the development of focal atherosclerotic lesions; however, these forces are difficult to measure directly. Instead, it has been proposed that artery geometry, as the primary determinant of local hemodynamics, could be a clinically feasible surrogate “local” risk factor for atherosclerosis. To date this hypothesis has not been satisfactorily tested, owing to superficial geometric surrogates of disturbed flow, small sample sizes (effect of systemic factors) and/or confounding effects of disease on geometry. The primary objective of this thesis was to test this “geometric risk hypothesis” via direct association of definitive geometric factors and an early atherosclerosis marker (e.g. wall thickness), made possible through our access to magnetic resonance imaging and risk factor data from the Atherosclerosis Risk in Communities’ Carotid MRI sub-study. First, it was shown that the 3D geometry of the carotid bifurcation could be characterized rapidly and reliably, even for routine clinical acquisitions. Second, two novel individual geometric variables were proposed, inspired by the influence of flare and tortuosity on flow separation, which were shown to improve the prediction of disturbed flow burden compared to “conventional” shape-based geometric variables. Third, these redefined geometric factors, but not their shape-based counterparts, were shown by multiple regression to be independent predictors of wall thickness, but only after thoroughly accounting for the secondary effects of wall thickening on geometry. These findings provide strong evidence for the geometric risk hypothesis of atherosclerosis in humans group study, and provide important guidance for future investigations of geometric risk; however, the incremental value of optimized geometric risk factors is questionable relative to conventional cardiovascular risk factors, which challenges their future clinical usage as additional non-modifiable local risk factors.

The use of transcranial Doppler (TCD) ultrasound for the assessment of cerebral blood flow velocity (CBFV) provides an indication of cerebral blood flow assuming the diameter of the insonated vessel remains constant. Studies using TCD have traditionally described cerebrovascular hemodynamics with respect to CBFV and cerebrovascular resistance (CVRi); however, a more complete assessment of the cerebral circulation can be gleaned from the analysis of within beat characteristic of the TCD velocity waveform for the determination of cerebrovascular tone. Therefore, the general purpose of the presented studies was to assess CBFV responses and within beat characteristic for the description of cerebrovascular hemodynamics after long duration spaceflight, with sustained orthostasis, in response to changes in the partial pressure of end tidal carbon dioxide (PETCO2), and with NG stimulation. After long duration spaceflight, cerebrovascular autoregulation was found to be impaired along with a reduction in cerebrovascular CO2 reactivity (Study 1). Additionally, critical closing pressure (CrCP) was found to be increased suggesting potential remodelling of the cerebrovasculature contributing to an increase in cerebrovascular tone (Study 2). With sustained orthostasis, CBFV was found to progressively decrease and to be related to reductions in PETCO2 and increases in CrCP suggesting the contribution of changes in cerebrovascular tone leading to the development of syncope (Study 4). The CBFV reduction with the progression towards syncope was also associated with changes in waveform morphology such that the dicrotic notch point was less than the end diastolic value (Study 3). Mathematical modelling (RCKL) was used to further assess changes in cerebrovascular hemodynamics for physiological interpretation of changes in CBFV waveform morphology and found that the amplitude of the dicrotic notch and the calculation of the augmentation index were both significantly related to vascular compliance before and after stimulation with NG (Study 5). The use of quantitative assessments of common carotid artery (CCA) blood flow as an indicator of cerebral blood flow suggested the dilation of the middle cerebral artery (MCA) with NG (Study 5 and 6) and changes in MCA diameter with acute alterations in PETCO2 (Study 6). CCA and MCA velocity wave morphology were assessed showing that with changes in PETCO2, changes in CBFV velocity wave were not reflected in the CCA trace (Study 7). In addition, further assessment of the CBFV velocity trace and the calculation of CrCP and the augmentation index suggested that with changes in PETCO2 cerebrovascular compliance and cerebrovascular tension, both thought to be components of cerebrovascular tone, change independently (Study 7). Combined, the results of the presented studies suggest that changes in cerebrovascular hemodynamics can be determined from alterations in the CBFV velocity waveform morphology. However, further work is required to determine how these variations relate to specific components of cerebrovascular tone, including alterations in cerebrovascular compliance and vascular tension, and how these variables change with acute and chronic alterations in cerebrovascular hemodynamics.

Thesis (Ph.D.)--University of Tasmania, 2005. / Includes 2 articles in back pocket. Includes bibliographical references.

Thesis (Ph.D.)--University of Western Australia, 2007.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Hanjoong Jo; Committee Member: Ajit Yoganathan; Committee Member: Dean P. Jones; Committee Member: Kathy K. Griendling; Committee Member: W. Robert Taylor

Thesis (doctoral)--Nijmegen, 1982.

Thesis (M.A.)--Marquette University, 2010. / Available for download on Dec. 7, 2010. John F. LaDisa, Lars Olson, Joseph Cava, Margaret Samyn, Kimberly Gandy, Laura Ellwein, Advisors.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). "17 July 2007." Includes bibliographical references (p. [345]-360). Also available via the World Wide Web.