Development of Multimodal Optical System Guided by Optical Coherence Tomography

The goal of this dissertation is to develop multimodal light scattering techniques using optical coherence tomography (OCT) to improve clinical diagnosis. OCT is a non-invasive optical imaging technique that utilizes low coherence interferometry to detect reflected and scattered light from a sample to produce depth resolved images. OCT is an emerging technology for a wide range of biomedical applications, with its largest impact in the field of ophthalmology to assess retinal morphology and abnormalities. Due to its excellent axial resolution, OCT has been often jointly used with a variety of other optical techniques in multimodal platforms for enhanced characterization of biological tissues.

The first section discusses the development of a multimodal optical system that combines OCT and angle-resolved low coherence interferometry (a/LCI). Similar to OCT, a/LCI utilizes low coherence interferometry for depth gating, but instead of imaging, it measures the angular dependence of scattered light as a function of depth to retrieve depth-resolved nuclear morphology measurements. However, since a/LCI is not an imaging modality, it can produce ambiguous results when the measurements are not properly oriented to the tissue structure. Utilization of OCT can resolve this problem, by providing real time image guidance for a/LCI and ensuring proper sample orientation. Moreover, OCT enables the co-registration of light scattering measurements to specific histological layers, which significantly improves the effectiveness of nuclear morphology determination. Thus, a multimodal system that combines OCT and a/LCI can provide a unique analysis of tissue structure that cannot be assessed using a standalone modality. Using the combined modality, this research develops quantitative biomarkers from ex vivo tissue samples to discriminate disease states.

The second portion of the work describes the development of a low-cost, portable OCT system that could significantly increase ease of access, particularly targeted for low resource settings. Although OCT has been adopted as the gold standard for retinal imaging in ophthalmology, the high cost of the clinical system has restricted access to mostly large eye centers and laboratories. Cost reduction and portability have been of interest for numerous optical technologies. Providing a comprehensive low-cost OCT system will open the doors for a wide variety of potential opportunities of OCT guided diagnosis. This section discusses the design and the implementation of a low-cost system, as well as a demonstration of the imaging capabilities that could meet the required performance for retinal imaging in clinical and laboratory studies.

The last section discusses the performance of imaging fiber bundles for light delivery and collection in endoscopic a/LCI. The use of imaging bundle for coherent imaging application has been limited since coherent imaging relies on single mode illumination, which requires expensive scanning optics, to reject higher mode interference. This section investigates the application of more affordable fiber bundles to replace such costly systems. A number of commercial and custom fiber bundles that could be used for light delivery and collection for the endoscopic probe have been carefully characterized. This characterization will not only help with developing a novel probe design for a/LCI, but also provide valuable insights into the potential application of coherent bundles for general coherent imaging including OCT.