Recent Publications and Presentations

Lo WCY, Uribe-Patarroyo N, Hoebel K, Beaudette K, Villiger M, Nishioka NS, Vakoc BJ, Bouma BE. Balloon catheter-based radiofrequency ablation monitoring in porcine esophagus using optical coherence tomography. Biomedical Optics Express [Internet]. 2019;10 (4) :2067-2089. Publisher's VersionAbstract

We present a microscopic image guidance platform for radiofrequency ablation (RFA) using a clinical balloon-catheter-based optical coherence tomography (OCT) system, currently used in the surveillance of Barrett’s esophagus patients. Our integrated thermal therapy delivery and monitoring platform consists of a flexible, customized bipolar RFA electrode array designed for use with a clinical balloon OCT catheter and a processing algorithm to accurately map the thermal coagulation process. Non-uniform rotation distortion was corrected using a feature tracking-based technique, which enables robust, frame-to-frame analysis of the temporal fluctuation of the complex OCT signal. With proper noise calibration, precise delineation of the thermal therapy zone was demonstrated using cumulative complex differential variance in porcine esophagus ex vivo with the integrated OCT-RFA system, as validated by nitroblue tetrazolium chloride (NBTC) histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to a wide range of epithelial lesions.

Lo WCY, Uribe-Patarroyo N, Hoebel K, Nam AS, Villiger M, Nishioka N, Vakoc B, Bouma B. Microscopic image guidance: real-time radiofrequency ablation monitoring for Barrett's esophagus (SIR 2017 Medical Student Scholar). Journal of Vascular and Interventional Radiology [Internet]. 2017;28 (2) :S199–S200. Publisher's VersionAbstract

Purpose: The term “image-guided therapy” has traditionally been confined to predominantly macroscopic imaging modalities (e.g., CT, MR, and US), which offer resolution on the order of mm, for guiding therapeutic interventions. Here, we introduce the concept of microscopic image guidance for real-time thermal therapy monitoring in epithelial lesions using optical frequency domain imaging (OFDI), which offers high-speed, high-resolution (10 mm) imaging in 3D. Our earlier clinical studies using our OFDI balloon catheters have shown promise in Barrett’s esophagus (BE) screening. This study aims to develop a versatile, OFDI-based thermal therapy monitoring platform to precisely target epithelial lesions, such as BE with dysplasia.

Materials: We developed a microscopic thermal therapy guidance platform that integrates a flexible bipolar radiofrequency ablation (RFA) electrode array around the clinical balloon OFDI catheter. Imaging was performed between consecutive electrodes in porcine esophagus ex vivo. We developed a therapy monitoring technique based on complex differential variance (CDV) that enables the direct, noninvasive visualization of the coagulation zone at high spatial resolution using real-time, dynamic fluctuations in the OFDI signals. This is contrary to conventional, temperaturebased RFA monitoring techniques, which are often invasive and only provide an indirect measure of tissue injury, or emerging techniques (e.g., MR and US thermometry) limited by spatial resolution.

Results: We demonstrated real-time, direct, label-free visualization of the coagulation process during RFA ablation at high-resolution using our integrated RFA therapy delivery and OFDI balloon catheter-based guidance system. Our histological analysis using nitroblue tetrazolium chloride (NBTC) frozen sections confirmed that the CDV-based technique accurately and directly delineates the thermal coagulation zone in porcine esophagus ex vivo.

Conclusions: The ability to delineate thermal lesions at high resolution opens up the possibility of performing microscopic image-guided procedures in numerous clinical applications, especially in epithelial lesions where the precise delivery of thermal energy is critical.

 

Laser thermal therapy monitoring using complex differential variance in optical coherence tomography (Featured in Jan 2017 issue)
Lo WCY, Uribe-Patarroyo N, Nam AS, Villiger M, Vakoc B, Bouma BE. Laser thermal therapy monitoring using complex differential variance in optical coherence tomography (Featured in Jan 2017 issue). Journal of Biophotonics [Internet]. 2017;10 (1) :84-91. Publisher's VersionAbstract

Conventional thermal therapy monitoring techniques based on temperature are often invasive, limited by point sampling, and are indirect measures of tissue injury, while techniques such as magnetic resonance and ultrasound thermometry are limited by their spatial resolution.  The visualization of the thermal coagulation zone at high spatial resolution is particularly critical to the precise delivery of thermal energy to epithelial lesions. In this work, an integrated thulium laser thermal therapy monitoring system was developed based on complex differential variance (CDV), which enables the 2D visualization of the dynamics of the thermal coagulation process at high spatial and temporal resolution with an optical frequency domain imaging system. With proper calibration to correct for noise, the CDV-based technique was shown to accurately delineate the thermal coagulation zone, which is marked by the transition from high CDV upon heating to a significantly reduced CDV once the tissue is coagulated, in 3 different tissue types ex vivo: skin, retina, and esophagus. The ability to delineate thermal lesions in multiple tissue types at high resolution opens up the possibility of performing microscopic image-guided procedures in a vast array of epithelial applications ranging from dermatology, ophthalmology, to gastroenterology and beyond. 

Longitudinal, 3D Imaging of Collagen Remodeling in Murine Hypertrophic Scars In Vivo using Polarization-sensitive Optical Frequency Domain Imaging (Featured on cover)
Lo WCY, Villiger M, Golberg A, Broelsch FG, Khan S, Lian CG, Austen WG, Yarmush M, Bouma BE. Longitudinal, 3D Imaging of Collagen Remodeling in Murine Hypertrophic Scars In Vivo using Polarization-sensitive Optical Frequency Domain Imaging (Featured on cover). Journal of Investigative Dermatology [Internet]. 2016;136 (1) :84-92. Harvard-MIT HST SpotlightAbstract

Hypertrophic scars (HTS), frequently seen after traumatic injuries and surgery, remain a major clinical challenge because of the limited success of existing therapies. A significant obstacle to understanding HTS etiology is the lack of tools to monitor scar remodeling longitudinally and noninvasively. We present an in vivo, label-free technique using polarization-sensitive optical frequency domain imaging for the 3D, longitudinal assessment of collagen remodeling in murine HTS. In this study, HTS was induced with a mechanical tension device for 4–10 days on incisional wounds and imaged up to 1 month after device removal; an excisional HTS model was also imaged at 6 months after injury to investigate deeper and more mature scars. We showed that local retardation and degree of polarization provide a robust signature for HTS. Compared with normal skin with heterogeneous local retardation and low degree of polarization, HTS was characterized by an initially low local retardation, which increased as collagen fibers remodeled, and a persistently high degree of polarization. This study demonstrates that polarization-sensitive optical frequency domain imaging offers a powerful tool to gain significant biological insights into HTS remodeling by enabling longitudinal assessment of collagen in vivo, which is critical to elucidating HTS etiology and developing more effective HTS therapies.

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