A Novel 3D Imaging Pipeline for Analyzing Radiofrequency Catheter Ablation in Preclinical Animal Models.

Authors: Gianna Ferron(1), Neil Patel(1), Anthony Knesis(1), Yookyung Jung(1), Stefan Linehan(1), Tim Ragan(1), Jay Budrewicz(2), David Parrillo(2), Rami Tzafriri(2)

Affiliations: (1) TissueVision, Inc., Newton, MA; (2) CBSET, Inc., Lexington, MA

Abstract:
Radiofrequency catheter ablation uses programmed electrical stimulation to alter or destroy cells causing irregular parenchymal activity. Despite its history of clinical adoption across a range of therapeutic areas, the 3D volume of ablated tissue has yet to be quantified. To address this gap, we developed a novel Serial Two-Photon Plus (STP2) pipeline to visualize and quantify ablated tissue through imaging of sub-micron cellular features across treated porcine liver and kidney samples. Porcine liver and kidney were treated ex vivo with an ablation pen at three timepoints (0, 20, and 40 seconds) and imaged with the STP2 pipeline using a TissueCyte system. The resulting high-resolution multi-channel datasets at 920 nm yielded 3D models of the label-free collagen matrix and cellular autofluorescence. Automated analysis pipelines were developed to extract the damaged area via detection of the autofluorescence intensity and characteristics of the collagen matrix. Resulting high resolution 3D models successfully isolated and quantified the ablated tissue volume, and characterized spatial changes in tissue texture for the three treatment timepoints in the liver and kidney. In addition, regional analysis quantified differences in fractional area, bundle frequency, and anisotropy of collagen fibers in treated samples. The STP2 pipeline produces translational high-throughput preclinical ablation data with enhanced sensitivity and precision, providing the ability to quantify changes in total ablation volume in tissues at different timepoints and power levels, in a variety of organs.