Investigating the Effectiveness and Mechanisms of Lymphaticovenous Anastomoses (LVA) for Lymphedema Treatment: Integrating Computational Modeling with Clinical LVA Insights

Project Summary/Abstract Lymphedema, a condition characterized by swelling and impaired lymphatic flow, affects a significant portion of the global population, particularly individuals undergoing cancer treatments involving lymphadenectomy and radiotherapy. Despite its prevalence, there is still a lack of comprehensive understanding of the underlying mechanisms driving lymphedema progression and the most effective treatment strategies. This project seeks to address these challenges through a multidisciplinary approach that combines biomechanics, computational modeling, and experimental data. The primary focus of this research is to study the lymphatic flow dynamics and adaptations in response to lymphaticovenous anastomoses (LVA), a surgical intervention commonly used to treat lymphedema. By collaborating with Chang-Gung Hospital, we have gained access to invaluable clinical data, including declassified patient data, which allows us to investigate the outcomes and impacts of both antegrade and retrograde anastomoses in treating lower limb lymphedema. This novel analysis platform provides unique insights into lymphatic function in vivo in humans, and we employ non-invasive imaging techniques to quantify lymphatic pump dynamics. Our research leverages a theoretical framework that integrates a lumped parameter model for lymphangion function and lymph transport, a microstructurally-motivated constitutive model for the mechanical behavior of isolated lymphatic vessels, and innovative models for acute mechanically-mediated vasoreactive adaptations and long-term volumetric growth. We simulate changes in muscle contractility and geometry of a single isolated lymphatic vessel in response to sustained elevation in afterload to understand the acute and long- term adaptations to mechanical loading. Furthermore, we develop computational models to investigate the effects of growth and remodeling (G&R) processes in the lymphatic vessel network in response to elevated loading conditions caused by LVA. This multi-scale approach considers the biomechanics at the tissue and cellular levels, aiming to determine the causative factors behind lymphatic failure and the potential impact of LVA on lymphangion loading. Through this project, we aim to gain deeper insights into the mechanosensitivity of the lymphatic vasculature and the implications of shear stress and pressure on lymphatic contractility. The findings from our research have the potential to advance our understanding of lymphatic flow regulation and the adaptation process in response to various loading conditions. Ultimately, this knowledge could lead to improved treatment strategies for lymphedema patients and potentially pave the way for more effective biomedical engineering interventions.