3D Dynamic Ultrasound Localization Microscopy

点击翻译按钮获取中文摘要

Microvessels are the smallest blood vessels (<100 microns) in the body. They distribute blood, and thus oxygen and nutrients, within tissues, and their dysfunction is central to many of our most pressing healthcare challenges, from heart failure to diabetes and neurodegenerative diseases. The tools available to image the anatomy and the in vivo function of these vessels have been improving rapidly but remain limited in both the laboratory and clinical settings, which hampers our ability to devise novel diagnostic techniques and therapeutic approaches. 2D blood vessel imaging using ultrasound has undergone multiple breakthrough innovations over the past 10 years. Most recently, a novel technique inspired by super-resolved fluorescence microscopy called ultrasound localization microscopy (ULM) improved spatial resolution of the vasculature from hundreds to a few microns in vivo via the detection at thousands of frames per second of millions of individual microbubbles (approved for human use) injected in the blood stream, enabling the generation of vascular maps of unprecedented resolution with any imaging modality that can probe at large depth. ULM remains however currently limited to static angiographic images in 2D imaging planes, of which the thickness can reach up to 1 mm, despite a 5-um in-plane resolution. We have recently introduced two innovations to ULM: the capability of performing images in vivo in 1) three dimensions with isotropic resolution and 2) dynamically. Together, these innovations, we believe, will be game changers in the field: achieving true isotropic superresolution, i.e., 5X5X5 um3 instead of 5X5X1000 um3 as currently obtained by state-of the-art ULM, and providing a millisecond temporal resolution, enable the generation of biomarkers currently invisible to existing modalities. Our long-term vision is to develop, validate and demonstrate feasibility of novel instruments and methodologies based on 3D-DULM for enhanced diagnosis and treatment monitoring of diseases associated with microvascular abnormalities. Our short-term objectives aim to fundamentally quantify the trade-offs between imaging parameters and image quality in order to extract new biomarkers, propose novel instrumentation designs, and enable the pre-clinical and clinical translation of 3D-DULM. Our general approach consists in innovating in the field of physics and to disseminate rapidly to preclinical and clinical applications by implementing collaborations with biologists and clinicians. Our technologies are based on ultrasound and as such are intrinsically portable, non-invasive, relatively low-cost and translational, as most parts of our devices can be used from small animals to humans. As such, they can rapidly be integrated into existing protocols and lead to immediate impact.