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Title: Improving clinical outcomes in renal HIFU therapy
Author: Ritchie, Robert Wilson
ISNI:       0000 0004 2735 2014
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
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The rising incidence of small, asymptomatic renal tumours discovered using abdominal imaging during the investigation of unrelated symptoms has fuelled the desire for new therapies which avoid surgical excision. Extracorporeal High Intensity Focused Ultrasound (HIFU) was proposed as one of these modalities but so far clinical research has been inconclusive. The present work was designed to improve these clinical outcomes through the conduct of further clinical trials, laboratory based research and the translation of new technology into existing HIFU devices. A Phase II clinical trial of patients (n=13) with newly diagnosed < 4cm renal tumours (clinical stage T1a) was designed, peer reviewed and received ethical approval (Ox REC 09/H0606/04). Ten of 13 patients underwent renal HIFU using a clinical HIFU device (Model JC/JC200, HAIFU, China). One patient could not be treated due to poor tumour visualisation after anaesthesia and two patients could not be treated as they became unwell before or during anaesthesia. Histological evidence of HIFU ablation in either tumour or normal renal parenchyma was seen in all ten patients. Evidence of sub-total tumour ablation was seen in 8/10 of patients. Grade 1 (< 50%), 2 (50-90%; & 3 (90-99%) ablation was achieved in 4/10, 3/10 & 3/10 patients respectively but complete (100%) tumour ablation was not possible. HIFU treatment caused minimal morbidity - no Grade III-V (Clavien-Dindo) complications related to HIFU treatment occurred. Grade I skin pain and induration was seen in 9/10 patients; Grade II skin pain occurred in a single patient. Patient demographics, imaging and tumour characteristics were used to design parameters to improve patient selection for renal HIFU. The tumour location, thickness of peri-nephric fat and renal nephrometry score were useful predictors of successful screening for treatment. Diligent use of these factors could limit unnecessary treatments and improve ablation outcomes. It is well known that ultrasound imaging of small renal masses can be challenging. Ultrasound imaging often deteriorates further during HIFU as the abdominal wall and fat tissues swell and cause increased attenuation. This loss of imaging quality was clearly demonstrated in this clinical trial and resulted in the early termination of treatment, before endpoints were reached, in a number of cases. The current clinical method for monitoring the success of HIFU ablation using hyperecho analysis of B-mode ultrasound images is also questionable. Laboratory based studies using ex-vivo bovine liver subjected to HIFU confirmed that hyperecho monitoring had low sensitivity, predictive values and overall accuracy. A novel method of HIFU monitoring - passive mapping of the emissions received from acoustic cavitation activity and other sources of non-linearity during HIFU treatment - is believed to represent a significant opportunity to improve feedback. This technique uses the passively received signature of cavity activity which, when time-reversed, gives high-resolution images of the precise location of the activity. Laboratory-based ex-vivo work, using a commercially available ultrasound system (, Zonare, USA), demonstrates its superiority over hyperecho monitoring. Indeed, thresholds could be applied to successfully predict HIFU ablation with high sensitivity and specificity. This technique was successfully translated into the clinical setting through the design of a Passive Acoustic Mapping (PAM) device. Custom-built receiving elements were applied without limiting the function of the existing HIFU devices. Both pre-clinical and ethically-approved clinical studies demonstrated its safe integration without significant impact on the device energy output or treatment accuracy. Using similar passive beamforming algorithms, acoustic cavitation activity was successfully mapped and corresponded with the location of thermal ablation in both ex-vivo tissue phantoms and during clinical HIFU therapy. It is believed that the development of new patient selection parameters will eliminate unnecessary investigation and treatment for those who are unsuitable. The use of PAM will lead to a significant improvement in the efficacy of treatment. It can be successfully applied to existing devices and predicts the location and extent of HIFU ablation with greater accuracy that existing techniques.
Supervisor: Coussios, C. C. ; Leslie, T. A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Oncology ; Radiology ; Urology ; Radiation ; Medical Sciences ; Applications and algorithms ; Tumours ; High Intensity Focussed Ultrasound (HIFU) ; Biomedical engineering