Implementation of 3D SHG imaging microscopy for tissue characterization and disease diagnostics: Experiment and simulations

Date of Completion

January 2010

Keywords

Engineering, Biomedical|Biophysics, General

Degree

Ph.D.

Abstract

This work encompasses the integrated use of 3D Second Harmonic Generation (SHG) imaging microcopy, Monte Carlo simulations and novel heuristic and phenomenological models to quantifiably characterize biological tissues and develop diagnostics for diseased states. Experimental techniques are utilized to obtain 3D SHG images and laser-tissue interaction descriptors, Monte Carlo techniques in conjunction with physical based models are used to determine bulk optical components (through inverse Monte Carlo techniques) and deconvolve the inter-related mechanisms responsible for the measured data. Utilizing this approach SHG creation attributes including efficiency and initial directionality are obtained which when combined with experimental data establish a comparative diagnostic suitable to quantifiably differentiate normal from the diseased tissues attributable to changes in the physical properties of the respective extracellular matrix (ECM). The analytical tool is developed and applied toward Osteogenesis Imperfecta in mice and Ovarian Cancer in humans, and a quantifiable diagnostic is developed. In addition this analytical tool is also utilized to better understand optical clearing of tissues which has the potential to achieve greater penetration into specimens of skeletal muscle tissue. ^

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