UC Irvine

Blood transports nutrients to organs and extracts waste products to maintain bodily functions. In physiology, the activities or changes related to blood flow are termed hemodynamics. Hemodynamics are regulated tightly to satisfy metabolic demands and maintain homeostasis. Altered blood flow can indicate the presence and progression of various diseases. Thus, hemodynamic measurements can offer diagnostic and prognostic information. Wide-field optical imaging (WFOI) is non-contact, non-radiative, and high-resolution imaging that is well suited for imaging superficial tissues such as skin or exposed brain. Despite its benefits, WFOI has limitations, such as shallow imaging depth and challenges in the proper interpretation of the measured data due to confounding factors associated with optical absorption and scattering by tissue constituents unrelated to blood. This research focused on two WFOI modalities: laser speckle imaging (LSI) and spatial frequency domain imaging (SFDI). LSI measures blood flow and SFDI measures scattering-independent chromophore (i.e., hemoglobin) concentrations. The confounding problems in these modalities are identified and solutions proposed for skin and brain imaging applications.Chapter 1 emphasizes the importance of considering epidermal melanin when interpreting SFDI data from the skin. We found that skin pigmentation can adversely affect optical measurements, especially scattering parameters, when an improper assumption is used during data processing. We further linked these effects to colorimetric measurements of melanin. The results collectively highlight the need for a better light transport model to handle the thin melanin layer and improve SFDI measurement accuracy. Chapter 2 focuses on how optical properties affect WFOI of cerebral hemodynamics. We created a system combining LSI with SFDI for widefield neuroimaging. A mathematical model derived from dynamic light scattering theory was used to correct LSI measurements of cerebral blood flow. This measurement enables direct comparison of blood flow measurements from multiple subjects and at different time points. We applied this imaging method on mice with Alzheimer’s disease (AD) and mid-life hypertension to study their cerebral hemodynamics and its connection to disease progression. The study aims to identify the connection between vascular health and the progression of AD and whether an antihypertensive treatment can rescue the condition. This is an ongoing study; however, preliminary data suggest that late mid-life hypertension induces dysregulated cerebral hemodynamics in mice with AD pathology when not treated. In summary, the research disseminated in this thesis highlights the need for proper consideration of confounding factors in WFOI of hemodynamics. These findings enable future efforts to improve the accuracy of WFOI measurements.