Title: Novel ultrasound methods for the detection and deflection of emboli in the bloodstream
Funder: Engineering and Physical Sciences Research Council

Abstract: Stroke affects approximately 150,000 people each year at a rate of one person every five minutes, and is the leading cause of adult disability, and third leading cause of death, in the UK (Stroke Association, UK). The majority of strokes are caused by pieces of plaque debris and blood-clots (emboli) that detach from the insides of diseased vessels and travel through the bloodstream to become lodged in the brain. Other sources of emboli include air bubbles entering the bloodstream during cardiovascular surgery, or formation of bubbles during sudden decompression (e.g. in Divers or Astronauts). Since emboli are carried rapidly through the bloodstream at speeds of up to 1 m/s, conventional ultrasound machines, that build up an image line-by-line, are too slow to capture their motion. Emboli are therefore not usually visible on ultrasound images. Currently, emboli are detected using the same 'Doppler principle' as used to detect speeding cars, which is great for detecting emboli speeding through arteries, but is unable to provide information on embolus size or composition. As large pieces of plaque and blood clots are much more hazardous than small bubbles, it is vitally important that clinicians can distinguish between them. Unfortunately, this is not possible using existing Doppler-based techniques. Therefore, we are keen to develop mew methods of determining embolus size and composition. This research utilises recent advances in ultrafast ultrasound imaging technology to capture the ultrasonic appearance and motion of emboli at high speed. Since large particles and tiny bubbles are expected to respond differently to the presence of an acoustic radiation force, this could potentially provide a method for distinguishing between them. If a sufficiently large acoustic radiation force can be directed toward the embolus this also has potential for altering the trajectories of emboli at arterial bifurcations to divert emboli away from the brain. Diversion of bubbles and debris may help to reduce the risk of brain injuries during surgical procedures and is not thought to be harmful to other organs. New methods for embolus detection and characterisation could also be useful for monitoring the sizes and compositions of emboli in patients. At present, many operations involving the heart and arteries carry a high risk of brain injury, which could potentially be avoided using embolus deflection devices. In addition to deflection of emboli away from vital organs, potential applications of our research include 'steering' of ultrasound microbubble contrast agents, or drugs, towards targets of interest. 1. The first part of our study investigates the potential for detecting solid particles and bubbles by relating the Doppler ultrasound scattering properties of emboli to their appearance in the ultrafast ultrasound image. Particular attention will be paid to examining the properties of solid and gas emboli that generate equivalent Doppler signals. 2. The second part of the study directs a focused ultrasound beam toward the moving embolus to slightly alter it's trajectory. As bubbles feel the 'push' of the ultrasound beam more strongly than solid particles, we expect that bubbles, thrombus, and plaque will generate differing responses to application of an acoustic radiation force, which will enable us to distinguish between them. 3. Finally, we investigate whether it would be feasible to direct a stronger acoustic radiation force to divert solid and gaseous emboli along one artery rather than another. This will be tested using physiologically realistic laboratory models. The ability to safely direct emboli away from the cerebral arteries, or toward targets of interest, has potential to reduce the number of emboli reaching the brain use during heart surgery, and improve the neurological safety of medical procedures involving the heart and arteries.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: STROKE