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Author ORCID Identifier

https://orcid.org/0009-0005-3051-2888

Date Available

9-21-2026

Year of Publication

2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Engineering

Department/School/Program

Biomedical Engineering

Faculty

Guoqiang Yu

Faculty

Sridhar Sunderam

Abstract

Adequate tissue blood flow and oxygenation are essential for maintaining cellular viability and normal organ function. Disruptions in microvascular perfusion and oxygen delivery contribute to ischemia- and hypoxia-related diseases, including stroke, cancer, retinopathy of prematurity (ROP), and mastectomy skin flap necrosis. Reliable, noninvasive approaches for assessing tissue hemodynamics are therefore critical for improving diagnosis and therapeutic decision-making, particularly in settings where conventional methods are limited. This dissertation investigates the clinical and physiological importance of measuring tissue blood flow and oxygenation across neonatal and surgical applications using both clinical monitoring and advanced optical imaging techniques. In the first study, high-speed pulse oximetry data were analyzed over the first 10 postnatal weeks to examine the relationship between intermittent hypoxemia (IH), defined as episodic drops in arterial blood oxygen saturation (SpO2), and the development of Type 1 ROP in preterm infants, a stage at which treatment is required. Using novel data analysis methods, we found that cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 was significantly associated with Type 1 ROP after adjustment for gestational age and birth weight. These findings improve our understanding of the impact of IH duration on the development of Type 1 ROP, highlight IH as a potentially modifiable factor, and provide insights for future interventions to improve visual outcomes in vulnerable preterm infants. In the second study, our laboratory developed a noncontact, dye-free speckle contrast diffuse correlation tomography (scDCT) system for depth-sensitive imaging of tissue blood flow to address the limitations of conventional superficial perfusion imaging. The scDCT system uses a galvo mirror to scan near-infrared point illumination across a selected region of interest, while a high-resolution scientific camera performs two-dimensional detection of spatial speckle contrast. The scDCT system was further extended to a multi-wavelength platform (MW-scDCT) for simultaneous imaging of tissue blood flow and oxygenation. Tissue blood flow was derived from speckle contrast, whereas tissue oxygenation was estimated from multispectral absorption changes using the modified Beer-Lambert law. The MW-scDCT system was evaluated in a rat skin flap model incorporating four flap types, Sham, Implant, Half Necrosis, and Full Necrosis, representing varying degrees of tissue viability. MW-scDCT enabled longitudinal imaging of tissue blood flow and oxygenation distributions, revealing significant differences among flap types and over time. Importantly, multivariable models combining both flow and oxygenation metrics improved the ability to distinguish necrotic from viable tissue compared with single-parameter approaches. In the third study, scDCT was translated to a clinically relevant porcine mastectomy skin flap model. Technical advances, including high-speed data acquisition, improved camera-galvo synchronization, an expanded field of view, and noise-correction algorithms, enabled reliable large-area imaging with deeper tissue penetration and reduced acquisition time. This technique successfully identified significant blood flow differences among flap types over time and demonstrated strong correlations with commercial indocyanine green angiography (ICG-A), used as a reference standard. These findings support the potential of scDCT/MW-scDCT as a noncontact, dye-free modality for perioperative assessment of flap viability. Future studies will evaluate the technology in clinical settings to support perioperative monitoring and management of tissue viability through real-time feedback and automated classification. In conclusion, this dissertation establishes the clinical relevance of blood flow and oxygenation as key physiological markers in neonatal care and surgical monitoring.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2026.99

Archival?

Archival

Funding Information

This study was supported by the National Institutes of Health (NIH) under grants R21-HD091118, R01-HD101508-01, R01-EB028792, R56-NS117587, and K23-HD109471, as well as support from the National Center for Advancing Translational Sciences (UL1TR001998). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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