Author ORCID Identifier

https://orcid.org/0000-0002-4689-990X

Date Available

10-3-2024

Year of Publication

2023

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department/School/Program

Biomedical Engineering

First Advisor

Dr. Guoqiang Yu

Second Advisor

Dr. Qiang Cheng

Abstract

Frequent measurement of cerebral hemodynamics is crucial for continuous assessment of brain function and health. Low-frequency oscillations (LFOs; < 0.1 Hz) have shown promise as an indicator of altered neurologic activity in the abnormal brain. Moreover, quantification of temporal correlations in LFOs across distinct brain regions enables mapping of regional neurovascular disorders. Portable diffuse optical techniques such as near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) enable noninvasive and continuous measurements of cerebral oxygenation and cerebral blood flow (CBF), respectively. However, most NIRS/DCS systems use limited numbers of discrete light sources and detectors and thus lack combinations of high temporal/spatial resolution and large field-of-view (FOV) for brain imaging. Recent development of an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) in our lab provides a low-cost and portable tool for high-density imaging of CBF distributions over large FOVs. The scDCT uses a galvo-mirror to remotely deliver coherent point near-infrared light to multiple source positions and a CMOS camera as a high-density 2-D detector array to quantify spatial fluctuations of diffuse laser speckles, resulting from movement of red blood cells. Boundary CBF data were input to a unique finite-element-method (FEM)-based reconstruction algorithm for 3-D imaging of CBF distributions. However, scDCT was hindered for extracting LFOs due to its low sampling rate. In this study, scDCT was optimized to achieve high sampling rates and fast image reconstructions by use of moving window algorithms with parallel computations (Project 1). Power spectral density (PSD) analysis was performed to investigate altered LFOs during transient cerebral ischemia in neonatal piglets. Transient cerebral ischemia caused reductions in both CBF and PSD, supporting inclusion of scDCT in the growing field of LFO analysis. One remaining limitation was the long computational time required for 3-D reconstruction, which prohibited real-time applications. To overcome this limitation, a depth-sensitive diffuse speckle contrast topography (DSCT) method was developed for analyzing scDCT data to achieve fast and high-density 2-D mapping of CBF distribution without the need of complex and time-consuming 3-D reconstructions (Project 2). New head-simulating phantoms with known optical/geometric properties were designed and fabricated to evaluate the spatial resolution and depth sensitivity of DSCT method. In-vivo experiments verified the capability of DSCT in tracking dynamic changes in CBF at different depths during CO2 inhalation and transient cerebral ischemia in rats. In addition to preclinical studies, a low-cost, wearable, fluorescence eye loupe (FLoupe) device was invented for intraoperative visualization of brain tumor margin in the clinic (Project 3). Consistent results were observed against an expensive, large, standard fluorescence operative microscope for the guidance of tumor resection. Overall, through 3 projects this dissertation demonstrated a variety of noninvasive noncontact optical technologies (scDCT, DSCT, and FLoupe) that enabled multiscale (rodents, piglets, and humans) and multimodality (CBF and fluorescence) imaging of brain hemodynamics and function. With further optimization and validation in large populations, these cost-effective portable optical imaging devices are appealing for continuous assessment of brain health at the bedside of clinic.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2023.411

Funding Information

This study was supported by :

  • American Heart Association (AHA) Predoctoral Fellowship (no.: 835726) (2021 - 2023)
  • National Institutes of Health (NIH) (Grant no.: R01 EB028792 (2020 - 2023), R01 HD101508 (2020 - 2025), R21 HD091118 (2018 - 2021), R56 NS117587 (2020 -2021), R01 AG062480 (2019 - 2024), R21 NS114771 (2020 - 2022)), and
  • Neuroscience Research Priority Area (NRPA) Pilot Grant (2021 - 2022) from the University of Kentucky.

Download

Share

COinS