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Title: Microbubbles in vascular imaging
Author: Dharmarajah, Brahman
ISNI:       0000 0004 8499 3926
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Ultrasound is integral in diagnostic imaging of vascular disease. It is a common first line imaging modality in the detection of deep vein thrombosis (DVT) and carotid atherosclerosis. The therapeutic use of ultrasound in vascular disease is also clinically established through ultrasound thrombolysis for acute DVT. Contrast agents are widely used in other imaging modalities, however, contrast enhanced ultrasound (CEUS) using microbubbles remains a largely specialist clinical investigation with truly established roles in hepatic imaging only. Aim The aim of this thesis was to investigate diagnostic and therapeutic roles of CEUS in vascular disease. Diagnostically, carotid plaque characteristics were evaluated for stroke risk stratification in patients with carotid atherosclerosis. Therapeutically, microbubble augmented ultrasound thrombolysis was investigated in-vitro as a novel technique for acute thrombus removal in the prevention of post thrombotic syndrome. Methods A validated in-vitro flow model of DVT was adapted and developed for a formal feasibility study of microbubble augmented ultrasound thrombolysis. Two cross sectional studies of patients with 50-99% carotid stenosis were performed assessing firstly, plaque ulceration and secondly plaque perfusion using CEUS. Results Using commercially available microbubbles and ultrasound platform, significantly improved thrombus dissolution was demonstrated using CEUS over ultrasound alone in the in-vitro flow model of acute DVT. In particular, increased destruction of the thrombus fibrin mesh network was observed. CEUS demonstrated greater sensitivity than carotid duplex in the detection of carotid plaque ulceration with a trend toward symptomatic carotid plaques. A reduced plaque perfusion detected by both semi-qualitative and quantitative analysis was associated with a symptomatic status in patients with a 50-99% stenosis. Conclusion CEUS is a viable adjunct to vascular imaging with ultrasound. Microbubble augmented ultrasound thrombolysis is a feasible, non-invasive, non-irradiating intervention which warrants further investigation in-vivo. Carotid plaque CEUS may contribute to future scoring systems in stroke risk stratification but requires prospective validation.
Supervisor: Davies, Alun ; Leen, Edward Sponsor: Stroke Association ; European Venous Forum ; Royal Society of Medicine Venous Forum ; Association of Surgeons in Training ; Graham-Dixon Charitable Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral