Development of Mechanical Optical Clearing Devices for Improved Light Delivery in Optical Diagnostics
Vogt, William C
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Biomedical optics is a rapidly expanding field of research focusing on the development of methods to detect, diagnose, and treat disease using light. While there are a myriad of optical systems that have been developed for biological tissue imaging, optical diagnostics, and optical therapeutics, all of these methods suffer severely limited penetration depths due to attenuation of light by tissue constituent chromophores, including cells, water, blood, and protein structures. Tissue optical clearing is a recent area of study within biomedical optics and photonics, where chemical agents have been used to alter tissue optical properties, reducing optical absorption and scattering and enabling light delivery to and collection from deeper tissue regions. However, there are concerns as to the safety and efficacy of these chemical clearing agents in vivo, especially in the skin, where the projective barrier function of the stratum corneum must be removed. Mechanical optical clearing is a recently developed technology which utilizes mechanical loading to reversibly modify light transport through soft tissues, and much of the work published on this technique has focused on applications in skin tissue. This clearing technique enables deeper light delivery into soft tissues but does not require use of exogenous chemicals, nor does it compromise the skin barrier function. While this clearing effect is thought to be resultant from interstitial water and blood transport, the underlying mechanism has not been concretely identified nor characterized. The hypothesis of this body of work was that interstitial transport of tissue chromophores (e.g. water and blood) causes intrinsic optical property changes, reduces tissue optical absorption and scattering, and improves light delivery in diagnostic applications. To test this hypothesis, we first developed a mathematical framework to simulate mechanical optical clearing, using both mechanical finite element models and optical Monte Carlo simulations. By directly simulating interstitial water transport in response to loading, data from mechanical simulations was combined with optical Monte Carlo simulations, which enabled prediction of light transmission measurements made during mechanical indentation experiments. We also investigated changes in optical properties during mechanical indentation using diffuse reflectance spectroscopy. These studies used controlled flat indentation by a fiberoptic probe to dynamically measure intrinsic optical properties as they changed over time. Finally, we apply mechanical optical clearing principles to functional near-infrared spectroscopy for neuroimaging. By building a prototypical mechanical optical clearing device for measuring cerebral hemodynamics, we demonstrated that mechanical optical clearing devices modify measured cerebral hemodynamic signals in human subjects, improving signal quality.
- Doctoral Dissertations