Design and development of optical reflectance spectroscopy and optical coherence tomography catheters for myocardial tissue characterization

Catheter ablation therapy attempts to restore sinus rhythm in arrhythmia patients by producing site-specific tissue modification along regions which cause abnormal electrical activity. This treatment, though widely used, often requires repeat procedures to observe long-term therapeutic benefits. This limitation is driven in part by challenges faced by conventional schemes in validating lesion adequacy at the time of the procedure. Optical techniques are well-suited for the interrogation and characterization of biological tissues. In particular, optical coherence tomography (OCT) relies on coherence gating of singly-scattered light to enable high-resolution structural imaging for tissue diagnostics and procedural guidance. Alternatively, optical reflectance spectroscopy (ORS) is a point measurement technique which makes use of incoherent, multiply-scattered light to probe tissue volumes and derive important data from its optical signature. ORS relies on the fact that light-tissue interactions are regulated by absorption and scattering, which directly relate to the intrinsic tissue biochemistry and cellular organization. In this thesis, we explore the integration of these modalities into ablation catheters for obtaining procedural metrics which could be utilized to guide catheter ablation therapy. We first present the development of an accelerated computational light transport model and its application for guiding ORS catheter design. A custom ORS-integrated ablation catheter is then implemented and tested within porcine specimens in vitro. A model is proposed for real-time estimation of lesion size based on changes in spectral morphology acquired during ablation. We then fabricated custom integrated OCT M-mode RF catheters and present a model for detecting contact status based on deep convolutional neural networks trained on endomyocardial images. Additionally, we demonstrate for the first time, tracking of RF-induced lesion formation employing OCT Doppler micro-velocimetry; this response is shown to be commensurate with the degree of treatment. We further demonstrate for the first time spectroscopic tracking of kinetics related to the heme oxidation cascade during thermal treatment, which are linked to tissue denaturation. The pairing of these modalities into a single RF catheter was also validated for guiding lesion delivery in vitro and within live pigs. Finally, we conclude with a proof-of-concept demonstration of ORS as a mapping tool to guide epicardial ablation in human donor hearts. These results showcase the vast potential of ORS and OCT empowered RF catheters for aiding intraprocedural guidance of catheter ablation procedures which could be utilized alongside current practices

Cardiac tissue characterization using near-infrared spectroscopy

Cardiac tissue from swine and canine hearts were assessed using diffuse reflectance near-infrared spectroscopy (NIRS) ex vivo. Slope measured between 800-880 nm reflectance was found to reveal differences between epicardial fat and normal myocardium tissue. This parameter was observed to increase monotonically from measurements obtained from the onset of radio frequency ablation (RFA). A sheathe-style fiber optic catheter was then developed to allow real-time sampling of the zone of resistive heating during RFA treatment. A model was developed and used to extract changes in tissue absorption and reduced scattering based on the steady-state diffusion approximation. It was found that key changes in tissue optical properties occur during application of RF energy and can be monitored using NIRS. These results encourage the development of NIRS integrated catheters for real-time guidance of the cardiac ablation treatment

Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called "precision medicine," the role of IA delivery for GBM is thoroughly reassessed

Stroke rehabilitation use and caregiver psychosocial health profiles in Singapore: a latent profile transition analysis

To identify and describe caregiver profiles based on their psychosocial health characteristics over a 12-month period and transitions among these profiles, to determine if stroke rehabilitation use at 12 months post-stroke differed by caregiver profile transition patterns, and to investigate if caregiver profiles at 3 months post-stroke moderate the association of stroke rehabilitation use at 3 months and 12 months post-stroke after accounting for covariates.National Medical Research Council (NMRC)This work was supported by a Health Services Research Competitive Research Grant (Project Number: HSRG/0006/2010) from the National Medical Research Council, Singapore