Flow Analysis in Pathological Microvascular Models by Ultrasound Localization Microscopy

This study presents a new class of ultrasound-compatible gelatin-based phantoms designed to mimic microvascular pathologies, such as vessel narrowing and blockages, in small arteries and arterioles. These phantoms enable detailed investigation of blood flow dynamics under pathological conditions. Using ultrasound localization microscopy (ULM), microbubble (MB) contrast agents are tracked to generate high-resolution velocity maps for assessing flow alterations within microvascular structures. MB velocities ranging from 0.01 to 25 mm s⁻¹ are quantified in phantoms with 60% and 80% constriction, demonstrating strong agreement with computational fluid dynamics (CFD) simulations. Phantoms with main channels of 500 µm and bifurcations narrowing to 200 and 100 µm are used to study the effects of geometric narrowing on flow dynamics. The redevelopment length of flow depended on narrowing severity and velocity, ranging from 0.2 to 0.85 mm for velocities of 3.3 to 33.3 mm s⁻¹. A four-outlet phantom replicated complex vascular structures to explore obstruction-induced flow alterations. This platform serves as a versatile tool for studying clinically relevant microvascular conditions, providing valuable insights into disease mechanisms and therapeutic strategies. By bridging imaging and translational research, this study highlights the potential of ULM and biomaterial-based phantoms to advance diagnostics and treatment of small vessel diseases.