Development of Portable Diffuse Optical Spectroscopic Systems For Treatment Monitoring

The goal of this dissertation is to demonstrate the utility of portable, small-scale diffuse optical spectroscopic (DOS) systems for the diagnosis and treatment monitoring of various diseases. These systems employ near-infrared light (wavelength range of 650nm to 950nm) to probe human tissue and are sensitive to changes in scattering and absorption properties of tissues. The absorption is mainly influenced by the components of blood, namely oxy- and deoxy-hemoglobin (HbO2 and Hb) and parameters that can be derived from them (e.g. total hemoglobin concentration [THb] and oxygen saturation, StO2). Therefore, I focused on diseases in which these parameters change, which includes vascular diseases such as Peripheral Atrial Disease (PAD) and Infantile Hemangiomas (IH) as well as musculoskeletal autoimmune diseases such as Rheumatoid Arthritis (RA). In each of these specific diseases, current monitoring techniques are limited by their sensitivity to disease progression or simply do not exist as a quantitative metric. As part of this project, I first designed and built a wireless handheld DOS device (WHDD) that can perform DOS measurements at various tissue depths. This device was used in a 15-patient pilot study for infantile hemangiomas (IH) to differentiate diseased skin from normal skin and monitor the vascular changes during intervention. In another study, I compare the ultra-small form- factor WHDD’s ability to monitor synovitis and disease progression during a patient’s treatment of RA against the capabilities of a proven frequency domain optical tomographic (FDOT) system that has shown to differentiate patients with and without RA. Learning from clinical utility of the WHDD from these two studies, I adapted the WHDD technology to develop a compact multi- channel DOS measurement system to monitor perfusion changes in the lower extremities before and after surgical intervention for patients with peripheral artery disease (PAD). Using this multi- channel system, which we called the vascular optical spectroscopic measurement (VOSM) system, our group conducted a 20-subject pilot study to quantify its ability to monitor blood perfusion before and after revascularization of stenotic arteries in the lower extremities. This proof-of- concept study demonstrated how DOS may help vascular surgeons perform revascularization procedures in the operating room and assists in post-operative treatment monitoring of vascular diseases

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

Wideband Watt-Level Spatial Power-Combined Power Amplifier in SiGe BiCMOS Technology for Efficient mm-Wave Array Transmitters

The continued demand for high-speed wireless communications is driving the development of integrated high-power transmitters at millimeter wave (mm-Wave) frequencies. Si-based technologies allow achieving a high level of integration but usually provide insufficient generated RF power to compensate for the increased propagation and material losses at mm-Wave bands due to the relatively low breakdown voltage of their devices. This problem can be reduced significantly if one could combine the power of multiple active devices on each antenna element. However, conventional on-chip power combining networks have inherently high insertion losses reducing transmitter efficiency and limiting its maximum achievable output power.This work presents a non-conventional design approach for mm-Wave Si-based Watt-level power amplifiers that is based on novel power-combining architecture, where an array of parallel custom PA-cells suited on the same chip is interfaced to a single substrate integrated waveguide (to be a part of an antenna element). This allows one to directly excite TEm0 waveguide modes with high power through spatial power combining functionality, obviating the need for intermediate and potentially lossy on-chip power combiners. The proposed solution offers wide impedance bandwidth (50%) and low insertion losses (0.4 dB), which are virtually independent from the number of interfaced PA-cells. The work evaluates the scalability bounds of the architecture as well as discusses the critical effects of coupled non-identical PA-cells, which are efficiently reduced by employing on-chip isolation load resistors.The proposed architecture has been demonstrated through an example of the combined PA with four differential cascode PA-cells suited on the same chip, which is flip-chip interconnected to the combiner placed on a laminate. This design is implemented in a 0.25 um SiGe BiCMOS technology. The PA-cell has a wideband performance (38.6%) with both high peak efficiency (30%) and high saturated output power (24.9 dBm), which is the highest reported output power level obtained without the use of circuit-level power combining in Si-based technologies at Ka-band. In order to achieve the optimal system-level performance of the combined PA, an EM-circuit-thermal optimization flow has been proposed, which accounts for various multiphysics effects occurring in the joint structure. The final PA achieves the peak PAE of 26.7% in combination with 30.8 dBm maximum saturated output power, which is the highest achievable output power in practical applications, where the 50-Ohms load is placed on a laminate. The high efficiency (>20%) and output power (>29.8 dBm) over a wide frequency range (30%) exceed the state-of-the-art in Si-based PAs