Cavitation-augmented perfusion in Peripheral Arterial Disease

Diabetes UK reported a significant (22.4%) rise in diabetes-related minor lower limb amputations in England, between 2015 and 2018. It is estimated that at least £1 in every £140 of NHS spending goes towards foot care for people with diabetes1.
Peripheral Arterial Disease (PAD) occurs due to a build-up of fatty deposits (atherosclerosis) within the lower extremity arteries, restricting blood flow and circulation, particularly to the feet. PAD is a major and increasing risk factor for diabetic patients, closely associated with lower extremity amputations2.
Ultrasound contrast agents are suspensions of stabilised microbubbles, originally developed for intra-vascular injection to provide contrast during diagnostic ultrasound imaging. In recent decades, research seeking to exploit contrast agent microbubbles as cavitation nuclei for interventional/therapeutic purposes, such as blood-clot dissolution for the treatment of Ischemic Stroke (sonothrombolysis), has intensified3. The ultrasound stimulated microbubble oscillations (cavitation) are thought to microvascular obstructions and promote reperfusion4.
This project will seek to develop cavitation-augmented perfusion for the treatment of PAD, that may ultimately be deployed and administered at home by the patient.

Key Objectives
Transducer design and fabrication for novel ultrasound exposure configurations.
Development of in-vitro models for mechanistic investigation and parameter optimisation.
Fabrication and testing of customised cavitation nuclei particles, including contrast agent microbubbles and acoustic vaporisation nanodroplets.
Preliminary translational studies in small animal models for validation.

FUSE has been designed to maximise impact in partnership with industry, international academics, and other organisations such as NPL and the NHS. It includes funded mechanisms to deal with opportunities in equality, diversity and integration (EDI) and in realisation of impactful outcomes.

EDI is aimed at realising the full potential of the talented individuals that join FUSE. Funding mechanisms include support for ten undergraduate internships to prime the pipeline into FUSE research studentships; part-time studentships reserved for people with specific needs to access this route; and talent scholarships for people from Widening Participation backgrounds. Additionally, cultural issues will be addressed through funded support for work life-balance activities and for workshops exploring the enhancement of research creativity and inventiveness through diversity.

People: As a community, FUSE will contribute to impact principally through its excellent training of outstanding people. At least 54 EngD and PhD graduates will emerge with very high value skills from the experience FUSE will provide in ultrasonics and through highly relevant professional skills. This will position them perfectly as future leaders in ultrasonics in the types of organisation represented by the partners.

Knowledge: FUSE will also create significant knowledge which will be captured in many different forms including industrial know-how, patents and processes, designs, and academic papers. Management of this knowledge will be integrated into the students' training, including data management and archival, and will be communicated effectively to those in positions to exploit it.

Economic Gain: In turn, the people and knowledge will lead to the economic impact that FUSE is ultimately designed to generate. The close interaction between the FUSE academics, its research students and industry partners will make it particularly efficient and, since FUSE includes both suppliers and customers, the transition from knowledge creation to exploitation will be accelerated.

Societal Benefit: FUSE is well placed to deliver a number of societal benefits which will reinforce our researcher training and external partner impacts. This activity encompasses new consumer products; improved public safety through advanced inspection across many industrial sectors; and new modalities for medical surgery and therapy. In addition, FUSE will provide engaging demonstrators to promote education in science, technology, engineering and maths, helping replenish the FUSE pipeline and supporting growth of the FUSE community far beyond its immediate members.

Impactful outcomes will gain from several specific funding mechanisms: horizon scanning workshops will focus on specific ultrasonic engineering application areas with industrial and other external participation; all FUSE students will have external partners and both industrial and international academic secondments will be arranged, as well as EngD studentships primarily in industry; and industry case studies will be considered. There will also be STEM promotion activity, funding ultrasonic technology demonstrators to support school outreach and public science and engineering events.