Advancements in angular domain optical imaging in biological tissues

Angular Domain Imaging (ADI) is a technique for performing optical imaging through highly scattering media. The basis for the technique is the micro-machined Angular Filter Array (AFA), which provides a parallel collection of micro-tunnels that accept ballistic/quasi-ballistic image-bearing photons and reject multiply scattered photons that result in image-destroying background noise. At high scattering levels, ADI image contrast declines due to the non-uniform scattered background light within the acceptance angle of the AFA. In this thesis, I developed multiple methodologies to correct for this problem and enhance ADI image contrast at higher scattering levels. These methodologies included combining ADI with time gating, polarization gating and employing image processing to estimate the background scattered light and use this information to enhance ADI image contrast and resolution. Furthermore, I conducted a comprehensive experimental investigation on a new AFA geometry designed to reduce the reflections within the micro-tunnels to reduce the unwanted background noise caused by multiply scattered photons. Building on previous studies with ADI in a trans-illumination configuration, I demonstrated that ADI could also be used to capture information-carrying photons from diffuse light back-reflected from tissue, where illumination was from the same side as the AFA. This mode of operation will enable applications of ADI where trans-illumination of samples is not possible. I also developed a tomographic ADI modality that rotated the sample and compiled ADI shadowgrams at each angle into a sinogram, followed by reconstruction of a transverse image with depth information. I also exploited the collimation detection capabilities of the AFA to extract photons emitted by a fluorophore embedded at depth within a turbid medium. The fluorescent imaging system using AFA offered higher resolution and contrast compared to a conventional lens and lens-pinhole fluorescent detection system in both in vitro and animal tests. Optical imaging with an AFA does not depend on coherence of the light source or the wavelength of light. Therefore, it is a promising candidate for multispectral/hyperspectral imaging to localize absorption and/or fluorescence in tissue and may have particular importance in cancer optical imaging.