Search

Cancer therapies usually depend on cross-sectional imaging for the assessment of treatment response. This study was designed to evaluate the ability of MRI to predict zones of necrosis following the use of high-intensity focused ultrasound (HIFU) to treat liver metastases. Patients with liver metastases, who had been scheduled for elective surgical resection of their tumours, were recruited to this non-randomized Phase II study. In each case, a proportion of an index liver tumour target was ablated. The response to HIFU was assessed after 12 days using contrast-enhanced MRI and compared directly with histological analysis at the time of surgery. Eight patients were treated, of whom six were subsequently assessed with both MRI and histology. There were no major complications. MRI predicted complete ablation in three cases. In each case, histological analysis confirmed complete ablation. In one case, the region of ablation observed on MRI appeared smaller than predicted at the time of HIFU, but histology revealed complete ablation of the target region. The predominant characteristic of HIFU-ablated tissue was coagulative necrosis but heat fixation was evident in some areas. Heat-fixed cells appeared normal under haematoxylin and eosin staining, indicating that this is unreliable as an indicator of HIFU-induced cell death. This study demonstrates that HIFU is capable of achieving selective ablation of pre-defined regions of liver tumour targets, and that MRI evidence of complete ablation of the target region can be taken to infer histological success.

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

High-intensity focused ultrasound (HIFU) has been investigated as a tool for the treatment of cancer for many decades, but is only now beginning to emerge as a potential alternative to conventional therapies. In recent years, clinical trials have evaluated the clinical efficacy of a number of devices worldwide. In Oxford, UK, we have been using the JC HIFU system (HAIFU Technology Company, Chongqing, PR China) in clinical trials since November 2002. This is the first report of its clinical use outside mainland China. The device is non-invasive, and employs an extracorporeal transducer operating at 0.8-1.6 MHz (aperture 12-15 cm, focal length 9-15 cm), operating clinically at Isp (free field) of 5-15 KWcm(-2). The aims of the trials are to evaluate the safety and performance of the device. Performance is being evaluated through two parallel protocols. One employs radiological assessment of response with the use of follow-up magnetic resonance imaging and microbubble-contrast ultrasound. In the other, histological assessment will be made following elective surgical resection of the HIFU treated tumours. Eleven patients with liver tumours have been treated with HIFU to date. Adverse events include transient pain and minor skin burns. Observed response from the various assessment modalities is discussed.

High intensity, focused ultrasound has considerable potential as a non-invasive surgical technique, with applications which include the treatment of benign prostatic hyperplasia and the elimination of metastatic disease in the liver. In this study, the use of MRI for treatment planning and subsequent monitoring of ultrasound therapy in the liver has been evaluated. In an experimental model both tumour bearing and normal liver lobes were treated invasively with high intensity focused beam ultrasound surgery. Subsequent changes in the tissue properties were investigated using MRI, in combination with the intravenous contrast agent, Gd-DTPA. The repair of ultrasound damaged tissue was followed until 8 weeks after treatment. The appearance of the MR images was compared with histological sections prepared from parallel experiments. Imaging and histology results showed excellent agreement, illustrating that MRI is well suited to the non-invasive observation of the effects of high intensity focused ultrasound therapy on tissue. Thus, as the clinical potential of ultrasound surgery is realized, MRI, together with the use of contrast agents, will be invaluable both in treatment planning and in monitoring the progress of a treated tumour.

Successful application of high intensity focused ultrasound to cancer treatment requires complete ablation of tissue volumes. In order to destroy an entire tumour it is necessary to place a contiguous array of touching lesions throughout it. In a study of how best to achieve this, exposures were selected to give single lesions that were thermal in origin, while avoiding effects due to tissue water boiling and acoustic cavitation. Arrays were formed in excised bovine liver. Under some exposure conditions, lesions were found to merge in front of the focal point, and failed to cover the desired volume. Using fine wire manganin-constantan thermocouples, temperature studies revealed a substantial rise in the temperature of surrounding untreated tissue. Cooling curves showed that it was necessary to allow surrounding tissue to cool for up to 2 min before ambient temperature was reached. By allowing the tissue to cool between exposures it was possible to form arrays of overlapping lesions thus successfully ablating the complete target region.