Date of Award
Doctor of Philosophy (PhD)
Combining optical excitation and ultrasonic detection, photoacoustic tomography (PAT) offers deep imaging with high resolution. With optical excitation, PAT maintains the high contrast of optical imaging. Because of the low scattering of ultrasonic waves in tissue, PAT achieves high spatial resolution at depths. Several advantages make PAT suitable for clinical application, including its scalable penetration and resolution, high optical absorption contrast, fast imaging speed, and ability to perform spectral decomposition. Based on different image reconstruction mechanisms, PAT can be further divided into two embodiments: raster-scanning-based photoacoustic microscopy (PAM) and reconstruction-algorism-based photoacoustic computed tomography (PACT). This dissertation aims to advance the direction of translational PAT, including both PAM and PACT.
In Chapter 1, I first explain the basic principles of PAM and PACT and then discuss in detail why they are suitable for translational studies. The chapter concludes with the motivation of my dissertation.
Chapter 2 introduces my translational studies in PAM. I first improved the systems lateral resolution and imaging penetration depth by applying an optical clearing technique. With glycerol as an optical clearing agent, the imaging performance of optical resolution PAM (OR-PAM) was greatly enhanced both in vitro and in vivo. Then I applied PAM in quantifying concentrations of blood substances, including red blood cells (RBCs) and bilirubin, and studied related diseases, such as RBC aggregation and jaundice. After building a model to statistically analyze photoacoustic signals for absolute measurement of red blood cell count, I developed multi-wavelength decomposition algorithms and implemented multi-wavelength PA imaging to map bilirubin concentration.
Chapter 3 describes studies of complex regional pain syndrome (CRPS) in patients with both OR-PAM and acoustic resolution PAM (AR-PAM). Blood vasculature and oxygen saturation (sO2) were imaged in eight adult patients with CRPS. Patients hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB. The results show that PAM can help diagnose and monitor CRPS.
Chapter 4 introduces my work on flow measurement both in mice and humans. It first discusses improving the flow measurement accuracy by a new technique cross-correlation-based flowmetry. This technique is based on OR-PAM and can effectively remove the particle size induced measurement error. I demonstrated this technique both in phantom and in vivo experiments in mice. To achieve flow measurement in the optical diffusive regime, I further developed two methods: saline-injection-based and cuffing-based flowmetries. The saline-injection-based method is especially pertinent to monitoring blood flow velocity in patients undergoing intravenous infusion, while the cuffing-based one is suitable for both patients and healthy people.
Chapter 5 presents my work on brain imaging, including both mouse and human brains in vivo. To achieve deep mouse brain imaging, I first used a ring transducer array (5 MHz center frequency) with an acoustic reflector. Blood vessels from the bottom of the mouse brain could be imaged, and many key features were detected, such as diving vessels, the superior sagittal sinus, and the posterior cerebral artery. However, the image contrast was not high due to the poor spatial resolutions of the system. To improve the image quality, I later used a linear array system with a 21 MHz center frequency. By rotating the linear array, more striking images were acquired. For the human imaging project, I successfully imaged blood vessel phantoms through an adult human skull.
Chapter 6 describes my work on melanoma imaging and depth measurement in patients. Two different systems were used in this project: a handheld AR-PAM system and a handheld linear array system. While the former is cheaper, the latter provides much faster imaging and a larger acceptance angle. With the array system, we successfully imaged melanomas in patients and achieved more accurate depth measurement than incisional biopsy in clinics.
Lihong V. Wang
Mark A. Anastasio, Jianmin Cui, Gregory Gregory, Baranidharan Raman,