A Multiscale Framework for In Silico Thrombus Generation and Photoacoustic Simulations

Abstract

Thrombus microstructure plays a critical role in determining the treatment success for thrombus-related diseases such as stroke and deep vein thrombosis. However, no in vivo diagnostic method can fully capture thrombus microstructure yet. Photoacoustic imaging is uniquely positioned to provide information on thrombi composition as it relays optical absorption information from diffuse photons at acoustic propagation depths. Computational modeling enables systematic exploration of microstructural effects on imaging signals, offering insights into developing improved in vivo diagnostic techniques. However, no photoacoustic simulation platform can model microstructural features within centimeter-scale phantoms at reasonable computational cost. Here, we present REFINE, a topology-driven framework for generating in silico thrombi replicating its key replicating their key microstructural traits. REFINE enables controlled, recursive optimization of thrombus topology, making it suitable for accurate photoacoustic modeling and potentially powerful for biomechanical analyses. These digital thrombi are embedded into a multiscale photoacoustic simulation platform that bridges microscale acoustic modeling with macroscale thrombus geometries, enabling efficient and realistic simulation of photoacoustic signal responses. We created unique thrombi microstructure for various compositions and porosities. Our simulation framework effectively links microstructural features to macroscale imaging outcomes, in agreement with previous empirical studies. Our results demonstrate that thrombus microstructure significantly affects photoacoustic spectral responses and can be modeled in silico. These findings highlight that multiscale photoacoustic simulation is a powerful tool for characterizing tissue microstructure and that our framework enables in silico thrombi analysis and diagnostic imaging strategy development