Intravascular photoacoustic imaging for cardiovascular disease management

A pressing need exists to detect vulnerable plaque in CVD, the number one killer in the United States. Vulnerable plaques possess high risk of rupture and causing thrombosis, which accounts for majority of fatal acute cardiovascular syndromes. Current medical imaging technologies are not able to accurately assess plaque vulnerability due to various limitations, especially the lack of chemical selectivity to visualize the key indicators of plaque vulnerability, such as the amount of lipid. My dissertation work involves the development of an intravascular device, named IVPA imaging system, to assess the plaque vulnerability by quantifying the lipid amount inside the arterial wall. Applying the overtone vibration transitions as the contrast, we demonstrated that lipid composition can be visualized inside the arterial wall, which opens up a great opportunity of diagnosis of atherosclerosis in vivo. Based on this concept, we first explored the optimal wavelength for excitation of the lipid molecules inside the arterial wall. We reported for the first time the employment of an optical window between 1600 nm and 1850 nm for bond-selective deep tissue imaging. In this window where a local minimum of water absorption resides, we found a 5 times enhancement of photoacoustic signal by first overtone excitation of the methylene group (CH2) at 1730 nm, compared to the second overtone excitation at 1210 nm. The enhancement allows 3-D mapping of intramuscular fat with improved contrast and of lipid deposition inside an atherosclerotic artery wall in the presence of blood. To distinguish the different components inside the arterial wall, we then demonstrate that lipids and collagen, two critical markers in many kinds of diseases, can be distinguished by hyperspectral PA imaging. The B-scan hyperspectral PA images, in which each pixel contains a spectrum, were analyzed by a MCR-ALS algorithm to recover the spatial distribution of collagen and lipids in both the phantom and arterial samples. Another major challenge in IVPA system is the slow imaging speed (~50 s per frame; 0.02 Hz) limited by the low repetition laser source, which hindered its translational potential. My thesis research overcame the challenge by demonstrating an IVPA system with the frame rate of 2 Hz by employing kHz-rate MOPA-pumped Ba(NO3)2 crystal-based Raman laser. This advancement increased the imaging speed of IVPA system ~ 2 orders of magnitude, and thus bridge the gap of translating the IVPA technology to clinical setting. With all the effort we made in the development of IVPA system, my dissertation research leads to a working prototype of IVPA system that is ready for in vivo animal study