Student Presentation -- Nathan Knighton
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Ph.D. Research Proposal, Monday June 17, 2019 -- Overcoming Barriers to Optical Biopsy in Pulmonary and Cardiac Applications

SMBB 4100, 2:00 pm

Speaker: Nathan Knighton. Advisor: Dr. Robert Hitchcock


Advances in fiber-optics based in vivo diagnostic techniques have led to the emergence of a new diagnostic field known as "optical biopsy." Optical biopsies allow for investigation of different types of tissue without removing the tissues from the body, and encompass several modalities of optical imaging. Fiber-optics confocal microscopy (FCM) is one such modality that has been FDA approved and promises to change the calculus of in vivo diagnostics. Recent studies have shown the ability of FCM to identify different types of cardiac tissue, including cardiomyocytes, blood vessels, epicardial fat, fibrotic tissue, Purkinje Fibers, and nodal regions. However, identification of tissue microstructures in these studies is limited to a depth of 100 microns and not the full tissue thickness. Therefore, FCM in the heart is fundamentally limited because the majority of cardiac tissue microarchitecture is well beyond the maximum focal depth of the system. In cardiac and other tissues, the ability to image tissue microarchitecture throughout the full tissue thickness is a critical barrier to progressing the field of optical biopsy.

Along with imaging depth, another barrier for currently approved optical biopsy probes is accessing tissues of interest within the body. For example, the latest generation of flexible bronchoscopes can only access roughly one-third of the human respiratory tract. If these barriers are overcome, the ability to identify tissue microarchitecture in vivo could change disease diagnosis through new understanding of tissue microstructure without removing tissue. The primary goals of this proposal are, therefore, to 1. Provide improved tissue access for currently approved optical biopsy in pulmonary applications; 2. Develop technology that advances the field of optical biopsy in cardiac applications. To achieve the first goal, we will develop a transbronchial access catheter to carry an existing FCM imaging probe in the lung that is compatible with the working channel of a flexible bronchoscope. To achieve the second goal, we propose a novel combination of machine learning with imaging to resolve backscatter spectra of deeply-penetrating broad-spectrum light that may lead to the development of a new catheterized imaging modality that is capable of characterizing cardiac tissue microstructure at depths approaching that of full-thickness atrial tissue.