Author ORCID Identifier

https://orcid.org/0000-0001-5683-9866

Date Available

9-11-2022

Year of Publication

2020

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department/School/Program

Biomedical Engineering

First Advisor

Dr. Guoqiang Yu

Abstract

Blood flow (BF) impacts the delivery of oxygen and nutrients to tissues and the removal of metabolic byproducts from tissues. Imaging of BF distributions helps characterize many diseases associated with tissue hypoxia/ischemia. The purpose of this study was to develop and validate a novel, noninvasive, noncontact, high-density camera-based speckle contrast diffuse correlation tomography (scDCT) device for use in both animal and human studies. The scDCT uses a galvo-mirror to remotely deliver the focused point near-infrared light to source positions and a sensitive 2D camera to quantify spatial diffuse speckle fluctuations, resulting from the movement of red blood cells in deep tissue (i.e., BF). The scDCT provides many advanced unique features over other competitive technologies, which may impact basic neuroscience research and clinical applications. These features include a fully noncontact system, quick data acquisition, adjustable source-detector patterns/density, flexible field of view, and cost-effective instrument. One remaining limitation in the scDCT prototype is the assumption of a semi-infinite tissue volume with a flat surface (i.e., slab). This assumption affects image reconstruction accuracy for tissues with irregular geometries. A photometric stereo technique (PST) was integrated into the scDCT system to acquire subject-specific tissue surface geometry for image reconstruction. Innovative use of one single camera for both PST and scDCT data collections obviated the need for complex alignment of sources and detectors on the tissue boundary. The performance of the integrated scDCT system was evaluated using computer simulations and by imaging BF variations in human forearms during artery cuff occlusion on upper arms. The clinical safety and feasibility were demonstrated by intraoperative imaging of BF distributions in mastectomy skin flaps. Eleven (11) patients undergoing mastectomy and breast reconstruction were imaged by a fluorescence angiography system (SPY-PHI, Novadaq) after the injection of indocyanine green (ICG). Because the ischemic areas have irregular shapes, an innovative contour-based algorithm was used to compare 3D images of blood flow and 2D maps of ICG perfusion. Significant correlations were observed between the two measurements around the ischemic areas, suggesting that scDCT provides vital information for intraoperative assessment of mastectomy skin flaps. Compared to SPY-PHI, our scDCT is fully noninvasive (dye-free), time-independent, and provides both 2D and 3D images of BF distributions. Furthermore, scDCT system was downscaled and optimized for 2D/3D imaging of cerebral blood flow (CBF) distributions in small rats through intact scalp and skull. The scDCT was used to continuously image global CBF increases during 10% CO2 inhalations (n = 9) and regional CBF decreases across two hemispheres during sequential ipsilateral and bilateral common carotid artery ligations (n = 8). The longitudinal imaging capability was demonstrated over a recovery period of 14 days after an acute stroke. These pilot studies demonstrate the capability of the innovative scDCT for imaging of BF distributions in tissues/organs with different sizes and irregular geometries. After further optimization and validation in large populations, the scDCT is expected to provide vital information for the diagnosis and management of vulnerable, ischemic, and hypoxic tissues.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2020.402

Funding Information

I acknowledge funding support from the National Institutes of Health [NIH, R01-CA149274 (2010 - 2016), R21-AR062356 (2012 - 2015), R21-HD091118 (2018 - 2021), R01 HD101508-01 (2020 - 2025), R01 EB028792-01 (2020 - 2023)], American Heart Association [AHA, Grant-In-Aid 16GRNT30820006 (2016 - 2019)], National Plastic Surgery Foundation [NPSF, Endowment 3048112770 (2017 - 2020)], and National Science Foundation [NSF, Established Program to Stimulate Competitive Research (EPSCoR) #1539068 (2015 - 2020)].

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