Year of Publication

2018

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department

Biomedical Engineering

First Advisor

Dr. Guoqiang Yu

Abstract

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle contrast followed with the next instrument, termed speckle contrast diffuse correlation tomography (scDCT). In scDCT, an optical switch sequenced coherent near-infrared light into contact-based source fibers around the sample surface. A fully noncontact reflectance mode device finalized improvements by combining noncontact scDCT (nc_scDCT) and diffuse fluorescence tomography (DFT) techniques. In the combined device, a galvo-mirror directed polarized light to the sample surface. Filters and a cross polarizer in stackable tubes promoted extracting flow indices, absorption coefficients, and fluorescence concentrations (indocyanine green, ICG). The scDCT instrumentation was validated through detection of a cubical solid tissue-like phantom heterogeneity beneath a liquid phantom (background) surface where recovery of its center and dimensions agreed with the known values. The combined nc_scDCT/DFT identified both a cubical solid phantom and a tube of stepwise varying ICG concentration (absorption and fluorescence contrast). The tube imaged by nc_scDCT/DFT exhibited expected trends in absorption and fluorescence. The tube shape, orientation, and localization were recovered in general agreement with actuality. The flow heterogeneity localization was successfully extracted and its average relative flow values in agreement with previous studies. Increasing ICG concentrations induced notable disturbances in the tube region (≥ 0.25 μM/1 μM for 785 nm/830 nm) suggesting the graduating absorption (320% increase at 785 nm) introduced errors. We observe that 830 nm is lower in the ICG absorption spectrum and the correspondingly measured flow encountered less influence than 785 nm. From these results we anticipate the best practice in future studies to be utilization of a laser source with wavelength in a low region of the ICG absorption spectrum (e.g., 830 nm) or to only monitor flow prior to ICG injection or post-clearance. In addition, ncDCT was initially tested in a mouse tumor model to examine tumor size and averaged flow changes over a four-day interval. The next steps in forwarding the combined device development include the straightforward automation of data acquisition and filter rotation and applying it to in vivo tumor studies. These animal/clinical models may seek information such as simultaneous detection of tumor flow, fluorescence, and absorption contrasts or analyzing the relationship between variably sized fluorescently tagged nanoparticles and their tumor deposition relationship to flow distributions.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2018.125

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