Date of Award
Doctor of Philosophy (PhD)
Photoacoustic Imaging (PAI) as an imaging method in biomedical research can provide high spatial resolution, various contrasts, great detection sensitivity, and deep penetration. These advantages are attributed to the combination of optical excitation and acoustic detection, which releases PAI from the ballistic limit faced by other optical imaging technique with high spatial resolution. In this dissertation, we aim to apply this technique to understand the connective tissue remodeling that is a ubiquitous physiological change in various medical complications.Chapter 1 elaborates the mechanism of PAI as well as the motivation of my dissertation.In Chapter 2, I introduce a new contrast mechanism for PAI, developed during this research. This contrast mechanism enables PAI to image the alignment of collagen fibers that make up connective tissue. Furthermore, the novel imaging method can measure both the amplitude of tissueճ dichroism and the orientation of the optic axis of uniaxial dichroic tissue. I experimentally demonstrate the performance of this method by imaging ex vivo connective tissue inside scattering media and successfully detect the orientation of the optic axis of uniaxial dichroic materials beyond the ballistic limit. The results show that the proposed method will extend the capability of PAI to imaging tissue absorption anisotropy.Chapter 3 describes the development of a transvaginal acoustic-resolution photoacoustic endoscope. The endoscope is 20 mm in diameter, rigid, and side-scanning. The scan is driven by a servo motor which provides a 10 Hz B-scan frame rate with a 30 scanning angle. I demonstrate the performance in phantom, ex vivo, and in vivo experiments. This device will be useful for monitoring physiological change associated with variation of blood oxygenation.Chapter 4 introduces a new method to quantify tissue hydration by measuring near-infrared spectra. I first demonstrate this method in hydrogel phantoms as an analog of connective tissue. Then, I apply this method to pregnant women in vivo, and observe an increase in the water content of the cervix throughout pregnancy. The application of this technique in healthcare may advance our understanding of connective tissue remodeling.Chapter 5 presents a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250 Hz B-scan rate over a 3 mm scanning range. Using this modality, I not only illustrate the morphological differences of vasculatures among human tissues, but also show the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.In chapter 6, I show how the tissue oxygenation, hydration, and vascularity change with cervical remodeling through pregnancy. In the study, I observe an overall increase of tissue hydration. In contrast, the tissue oxygenation does not change much. As future work, a systematic study illustrating the role of cervical remodeling in complications of preterm labor should focus on high-risk populations.
Yong Wang, Quing Zhu, Chao Zhou, Molly Stout,