Development and applications of optical imaging techniques for microcirculation and cardiovascular imaging
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The work presented in this thesis describes the development and applications of optical imaging techniques, optical coherence tomography (OCT) and photoacoustic (PA) imaging, for the purpose of diagnosing and treating diseases which are related to the microcirculation, skin conditions and the cardiovascular system. The feasibility of correlation mapping OCT (cmOCT) for in vivo imaging of human microcirculation under diseased conditions was demonstrated. The cmOCT technique uses standard OCT image acquisition and post processing software based on correlation statistics. cmOCT was used for in vivo microcirculation imaging of human forearm under normal and psoriatic conditions. The cmOCT technique has been found promising in terms of sensitivity and computational time for in vivo microcirculation imaging beneath human skin under normal and diseased conditions. The cmOCT generated microcirculation maps of the healthy tissue and psoriatic plaque provide adequate resolution in a totally non-invasive manner. The presented results indicate that cmOCT allows not only the identification of the microvessels, but also produces more detailed microvascular networks showing how the blood vessels relate to each other in healthy tissue and within the plaque. The feasibility of intra-coronary OCT correlation mapping to investigate the role of coronary microvessels in human atherosclerosis was also studied. A pre-clinical combined PA and ultrasound (US) imaging system, based on a multi-element linear-array transducer combined with multichannel collecting system, was optimised for human imaging under normal and diseased conditions. In vivo 3D co-registered PA/US structural and functional images from different sites within human skin such as forearm, breast and carotid were obtained using a range of high frequency transducer probes (15 MHz to 40 MHz). The linear-array based PA imaging has been found promising in terms of resolution, imaging depth and imaging speed for clinical applications. However, significant challenges remain, particularly with the imaging depth. High frequency linear-array transducer probes used in this study are similar in style, shape and use to regular hand-held clinical ultrasound probes, which can easily be acoustically coupled to the skin and moved around while imaging in real time. We believe that a reflection type probe used in this study is most likely to succeed in clinical applications. Its advantages include ease of use, speed and familiarity for radiographers and clinicians. Co-registered high frequency PA/US was used in the assessment of mesenchymal stem cells (MSCs) induced neovascularization/angiogenesis in vivo. In the first study, combined PA and US imaging, operated with 40 MHz frequency linear-array transducer probe was used in the assessment of topical human MSCs seeded in Excellagen™ scaffold based treatment to a dermal wound on the rabbit ear skin. In the second study, combined PA and US imaging, operated with 21 MHz frequency linear-array transducer probe and micro computed tomography (μCT) were used in the assessment of reparative ability of differentiated MSCs in a rat critical size bone repair defect model. Linear-array based co-registered PA/US imaging has been found promising in terms of non-invasiveness, sensitivity, adaptability, high spatial and temporal resolution at sufficient depths for the assessment of MSCs induced neovascularization/angiogenesis in vivo. A correlation between fractional flow reserve (FFR), a gold standard in the functional assessment of coronary artery stenosis, and intracoronary frequency domain OCT (FD-OCT) derived anatomical and blood flow measurements were determined. The diagnostic efficiency of FD-OCT derived these measurements in identifying severe coronary stenosis as determined by FFR was also determined. Blood flow measurements in coronary artery stenosis were derived from the volumetric analysis of the vessel segments imaged by FD-OCT. We found a weak but significant (p<0.05) correlation between FFR values and FD-OCT measured anatomical parameters; minimal lumen area (MLA), minimal lumen diameter (MLD) and percent area stenosis (%AS) in a study performed on 30 patients. In the overall group, the FD-OCT measured MLA and MLD have moderate diagnostic efficiency in identifying the severity of stenosis. FD-OCT measured MLA has high efficiency in identifying significant stenosis in vessels having reference diameter less than 3 mm. We found a good and significant correlation between FFR and FD-OCT derived blood flow measurements; stenosis resistance and FFR. The FD-OCT derived stenosis resistance and FFR have high diagnostic efficiency in identifying the severity of stenosis. The assessment of coronary artery stenosis severity based on FD-OCT derived these measurements can overcome many technical limitations of the quantitative coronary angiography and intravascular ultrasound and have potential to become helpful tool in the assessment of coronary artery disease.