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Four-dimensional X-ray velocimetry for biological applications
thesisposted on 06.02.2017, 02:58 by Dubsky, Stephen
The aim of this research was to develop motion measurement methods suitable for investigation of the dynamics of the cardiovascular and pulmonary systems. The methods developed represent critical advances in the field of functional biological imaging, and pave the way for further enhancement of our understanding of normal and pathological biological function. The thesis consists of three peer-reviewed journal articles, framed by substantial introductory and explanatory text. A thorough review of the literature identified significant limitations to the current methods for full-field measurement of vascular flow and lung function. Specifically lacking was the capability to measure four-dimensional (4D) motion fields at high spatial and temporal resolution. This capability is critically important for quantitative study of the function of the cardiovascular and pulmonary systems, for which function is intimately linked to motion. Two techniques were developed and applied. The approach was to combine synchrotron phase-contrast X-ray imaging with elements from computed tomography and particle image velocimetry, to provide the capacity for dynamic 4D measurement and the opportunity for quantitative data analysis. Computed tomographic X-ray velocimetry was developed and applied to in vitro vascular models. This method directly reconstructs three-dimensional motion fields from two-dimensional cross-correlations calculated from projection image pairs, without the need to first reconstruct 3D images of the sample. An extensive in silico parametric study found that the method was capable of accurate three-dimensional motion measurement from as few as 3 viewing angles. The limited number of projection angles required has the benefit of a significantly reduced X-ray radiation dose being delivered to the sample when compared with traditional computed tomography methods, a key requirement for measuring flow in living samples. Application to in vitro blood flow measurement demonstrated the effectiveness of this method for measurement of complex three-dimensional fluid flow fields. A method for high-resolution measurement of lung tissue motion and flow was developed, rigorously validated and applied to in vivo lung function measurement in mouse and rabbit pup models. The method provides the unique capacity to measure flow within the bronchial tree, throughout the breathing cycle. The method allows study of lung function in unprecedented detail, and will lead to new approaches to the study and diagnosis of various lung diseases.