Development of rotary intravascular catheter systems based on optical coherence tomography for multimodal imaging and therapy

Abstract

Coronary artery disease (CAD) is one of the highest mortality diseases worldwide. Because rupture of atherosclerotic plaque causes majority of fatal clinical complications, it is important to detect vulnerable plaques. To accurately detect vulnerable plaque, a catheter-based optical coherence tomography-near infrared fluorescence imaging (OCT-NIRF) that simultaneously provides structural-molecular information has been developed for diagnosing atherosclerosis. The utility of the catheter-based OCT-NIRF in the diagnosis of coronary artery disease has been demonstrated by a variety of preclinical studies. Future studies of the catheter-based OCT-NIRF should proceed in three directions. The first is translation to clinical application. Obtaining approval from the Food and Drug Administration (FDA) for exogenous fluorescence agent used in NIRF is challenging. For clinical translation, an imaging modality that can acquire molecular information without exogenous fluorescence agent is needed. The second is OCT-NIRF image-guided treatment. Since the ultimate objective of the catheter-based OCT-NIRF is to help in treatment of coronary artery disease, there is a need for study on how to use OCT-NIRF images to help with treatment. The third is solving problems degrading OCT-NIRF image quality. There are some factors degrading image quality. In order to increase the utilization of catheter-based OCT-NIRF, study to improve image quality is needed. In this thesis, three studies mentioned above were conducted. First, a catheter-based OCT-fluorescence lifetime imaging microscopy (FLIM) has been developed for translation to clinical application. FLIM can provide biochemical information which is necessary to diagnose the coronary artery disease without any exogenous contrast agent, utilizing the autofluorescence of the tissue itself under UV excitation. Since exogenous contrast agent is not needed, it can be easy to clinical translation. However, the spectral range used in OCT and FLIM was so broad that it is difficult to develop a rotary joint with high efficiency in the broad spectral range due to chromatic shift. This challenge has been overcome controlling core size of optical fibers. Through animal study, the catheter-based OCT-FLIM’s clinical feasibility for characterizing structural and biochemical features of the atherosclerosis has been demonstrated. Second, the catheter-based OCT-NIRF-photodynamic therapy (PDT) rotary system has been developed. PDT is one of the phototherapy methods which is useful where localized treatment is needed such as coronary artery disease. Studies applying PDT to coronary artery disease shows that the PDT can stabilize and regress the plaques. However, precise assessment of treatment effect is challenging. If treatment effect would be guided by OCT-NIRF, the catheter-based OCT-NIRF-PDT can be a very promising theranostic tool. However, if a scattering pattern is formed on optical fiber as conventional PDT diffusing catheter manufacturing method for a thin optical fiber used in OCT-NIRF, the optical fiber becomes mechanically unstable. This technical challenge has been overcome by controlling refractive index instead of making scattering pattern. The catheter-based OCT-NIRF-PDT shows feasibility of performing diagnosis and treatment with a single catheter. Finally, for enhancing image quality, noise-suppressing and astigmatism-correcting methods have been proposed. Due to the cross-talk between the core and the cladding of double clad fiber (DCF), noise can be occurred in OCT image. Since cause of the noise is OCT light guided through the DCF cladding, the noise was suppressed by reducing the density of the light guided through the cladding. Thus, the noise problem in the OCT image has been significantly solved. Astigmatism is caused by negative cylindrical lens effect of imaging sheath. The astigmatism was corrected by positive cylindrical lens effect of epoxy window and cylindrical surface of optical fiber. Thus, lateral resolution and signal-to-noise (SNR) can be improved by correcting astigmatism. In conclusion, the catheter-based OCT-FLIM and OCT-NIRF-PDT have been developed for intravascular imaging and therapy. Methods for improving the imaging quality of the intravascular OCT have also been developed. These newly developed catheter-based rotary systems and image quality methods are expected to be widely used in a variety of biomedical imaging and treatment fields, including coronary artery disease.