ICorps- A Numerical Platform for Microbubble Enhanced Sonothrombolysis

Dynaflow, Inc., Jessup MD

Investigators

Abstract

 Executive Summary of Predicate SBIR or STTR Phase I Grant and Team The ultimate objective of the parent SBIR Phase I award that started on Sep. 17, 2024 is to develop a numerical platform which can serve as a research tool during therapy discovery and a treatment planning system (TPS) during pre-operation planning in clinic, to significantly accelerate the clinical deployment of microbubble-augmented focused ultrasound (MBaFUS) for non- or minimally invasive thrombolysis. Sonothrombolysis has been successfully demonstrated in the lab of our NCSU partners to present both improved efficacy and enhanced safety over conventional treatment methods for thrombosis, which is a leading cause of death and disability in the United States. However, due to the complex multiple inter- coupled mechanisms involving MB dynamics, viscoelastic structure dynamics, MB-flow and MB cloud- blood clot interactions, the physics of MBaFUS for thrombolysis is not well understood yet, thus finding optimized treatment parameters for a patient-specific condition is difficult. This poses a major barrier to effective clinical applications and calls for a powerful TPS of sonothrombolysis. During the 1st week of project kickoff and execution, we realized a) the risks of project management due to the interdependency of major tasks; and b) the difficulties to conduct sufficient experiments due to the budget limit of Phase I; Also there’re c) potential pitfalls of TPS design due to the lack of expertise and resources for a deep understanding of customer needs. To address a), the main tasks are decomposed into sub-tasks which are able to be conducted in parallel among different subgroups. For example, while the structure subgroup is working on the modeling and coding of clot structure dynamics, the MB subgroup has started the parametric study of MB cloud interacting with and resulting stress on a rigid structure, which reveals that a spherical MB cloud leads to much more disruptive power than a cylindrical MB cloud. This trend will be validated first in experiments and then used to greatly narrow down the experimental conditions, i.e. to overcome not only a) but also b). Finally, concerning c), we appreciate the opportunities to work with the Industry Expert (IE) through I- Corps program which will result in necessary adjustments to our development roadmap to make it product- oriented, rather than technology-driven. Therefore, by leveraging the I-Corps discoveries, the completion of the parent SBIR Phase I will not only successfully reach the objective of proof of concept, but also lay a solid foundation of commercialization plan for the potential Phase II and its following full commercialization. During the parent Phase I, the specific aims bellow will be achieved: Aim 1: Enable TPS-MBaFUS to predict structure dynamics, such as blood clot surface morphology and clot rupture in the MB cloud-enhanced acoustic field, by developing and incorporating, in an Implicit Fluid- Structure Interaction (IFSI) mode, constitutive models for mixture materials involving tissues and blood clots, along with a two-way coupled Lagrangian MB modeling. Aim 2: Conduct well-controlled and high-quality experiments (in vitro in Phase I and in vivo in Phase II) to validate code predictions, such as MB cavitation and induced flow, clot morphology, MB cloud motion, and clot lysis rate under various MB, ultrasound, and clot conditions. Aim 3: An effective, productive and practical commercialization plan for Phase II application Our proposed I-Corps team will include the following three members, who are all committed to the time requirements of the program. Member Name Role William Plishker, PhD  C-Level Corporate Officer (CEO): Chao-Tsung Hsiao, PhD  Technical Lead (TL): Jingsen Ma, PhD  Industry Expert: Bei Ma, MS