This thesis presents the development of new optical coherence tomography imaging systems and techniques to improve in vivo 3D microvascular imaging. Specifically these systems and techniques were proposed to address three main problems with 3D Doppler optical coherence tomography imaging: (a) Motion artefacts, (b) angle dependence of the signal, and (c) relatively high minimum detectable velocity of conventional color Doppler algorithms (~500 μm/s). In order to overcome these limitations a multi-pronged strategy was employed: (1) Construction of a retrospectively gated OCT system for the mitigation of periodic motion artefacts. Proof of principle in vivo B-mode imaging of Xenopus Laevis (embryo of African clawed frog) cardiovascular function up to 1000 frames per second (fps) from data acquired at 12 fps. Additionally, 4D imaging of the Xenopus Laevis heart at 45 volumes per second was demonstrated. (2) Construction of a Fourier domain mode locked laser for high speed swept source optical coherence tomography imaging. This laser was capable of reaching sweep rates of 67 kHz and was optimized to function in the SNR limited phase noise regimes upto approximately 55 dB structural SNR. (3) Development of a novel speckle variance image processing algorithm for velocity and angle independent 3D microvascular imaging. The velocity and angle independence of the technique was validated through phantom studies. iii In vivo demonstration of the speckle variance algorithm was performed by imaging the capillary network in the dorsal skin-fold window chamber model, with the results being validated using fluorescence confocal microscopy. In the final part of this thesis, these newly developed technologies were applied to the assessment of anti-vascular and anti-angiogenic therapies in preclinical models, specifically, photodynamic therapy and targeted degradation of HIF-α.

This thesis presents the development of new optical coherence tomography imaging systems and techniques to improve in vivo 3D microvascular imaging. Specifically these systems and techniques were proposed to address three main problems with 3D Doppler optical coherence tomography imaging: (a) Motion artefacts, (b) angle dependence of the signal, and (c) relatively high minimum detectable velocity of conventional color Doppler algorithms (~500 μm/s). In order to overcome these limitations a multi-pronged strategy was employed: (1) Construction of a retrospectively gated OCT system for the mitigation of periodic motion artefacts. Proof of principle in vivo B-mode imaging of Xenopus Laevis (embryo of African clawed frog) cardiovascular function up to 1000 frames per second (fps) from data acquired at 12 fps. Additionally, 4D imaging of the Xenopus Laevis heart at 45 volumes per second was demonstrated. (2) Construction of a Fourier domain mode locked laser for high speed swept source optical coherence tomography imaging. This laser was capable of reaching sweep rates of 67 kHz and was optimized to function in the SNR limited phase noise regimes upto approximately 55 dB structural SNR. (3) Development of a novel speckle variance image processing algorithm for velocity and angle independent 3D microvascular imaging. The velocity and angle independence of the technique was validated through phantom studies. iii In vivo demonstration of the speckle variance algorithm was performed by imaging the capillary network in the dorsal skin-fold window chamber model, with the results being validated using fluorescence confocal microscopy. In the final part of this thesis, these newly developed technologies were applied to the assessment of anti-vascular and anti-angiogenic therapies in preclinical models, specifically, photodynamic therapy and targeted degradation of HIF-α.