Robert W. Ritchie

Spatiotemporal Monitoring of High-Intensity Focused Ultrasound Therapy with Passive Acoustic Mapping

PURPOSE To demonstrate feasibility of monitoring high-intensity focused ultrasound (HIFU) treatment with passive acoustic mapping of broadband and harmonic emissions reconstructed from filtered-channel radiofrequency data in ex vivo bovine tissue. MATERIALS AND METHODS Both passive acoustic emissions and B-mode images were recorded with a diagnostic ultrasound machine during 180 HIFU exposures of five freshly excised, degassed bovine livers. Tissue was exposed to peak rarefactional pressures between 3.6 and 8.0 MPa for 2, 5, or 10 seconds. The B-mode images were analyzed for hyperechoic activity, and threshold levels were determined for the harmonic (1.17 mJ) and broadband (0.0137 mJ) components of the passively reconstructed source energy to predict tissue ablation. Both imaging methods were compared with tissue lesions after exposure to determine their spatial accuracy and their capability to help predict presence of ablated tissue. Performance of both methods as detectors was compared (matched-pair test design). RESULTS Passive mapping successfully aided prediction of the presence of tissue ablation more often than did conventional hyperechoic images (49 of 58 [84%] vs 31 of 58 [53%], P < .001). At 5.4-6.3-MPa exposures, sensitivity, specificity, negative predictive value, and positive predictive value of the two methods, respectively, were 15 of 20 versus five of 21 (P = .006), eight of nine versus eight of nine (P = .72), 15 of 16 versus five of six (P = .53), and eight of 13 versus eight of 24 (P = .011). Across HIFU exposure amplitude ranges, passive acoustic mapping also aided correct prediction of the visually detected location of ablation following tissue sectioning in 42 of 45 exposures for which the harmonic and broadband threshold levels for tissue ablation were exceeded. Early cavitation activity indicated the focal position within the tissue before irreversible tissue damage occurred. CONCLUSION Passive acoustic mapping significantly outperformed the conventional hyperecho technique as an ultrasound-based HIFU monitoring method, as both a detector of lesion occurrence and a method of mapping the position of ablated tissue.

Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up.

Study Type – Therapy (case series)
Level of Evidence 4

High-intensity focused ultrasound treatment of liver tumours: post-treatment MRI correlates well with intra-operative estimates of treatment volume

OBJECTIVES To assess the safety and feasibility of high-intensity focused ultrasound (HIFU) ablation of liver tumours and to determine whether post-operative MRI correlates with intra-operative imaging. METHODS 31 patients were recruited into two ethically approved clinical trials (median age 64; mean BMI 26 kg m(-2)). Patients with liver tumours (primary or metastatic) underwent a single HIFU treatment monitored using intra-operative B-mode ultrasound. Follow-up consisted of radiology and histology (surgical trial) or radiology alone (radiology trial). Radiological follow-up was digital subtraction contrast-enhanced MRI. RESULTS Treatment according to protocol was possible in 30 of 31 patients. One treatment was abandoned because of equipment failure. Transient pain and superficial skin burns were seen in 81% (25/31) and 39% (12/31) of patients, respectively. One moderate skin burn occurred. One patient died prior to radiological follow-up. Radiological evidence of ablation was seen in 93% (27/29) of patients. Ablation accuracy was good in 89% (24/27) of patients. In three patients the zone of ablation lay ≤2 mm outside the tumour. The median cross-sectional area (CSA) of the zone of ablation was 5.0 and 5.1 cm(2) using intra-operative and post-operative imaging, respectively. The mean MRI:B-mode CSA ratio was 1.57 [95% confidence interval (CI)=0.57-2.71]. There was positive correlation between MRI and B-mode CSA (Spearmans r=0.48; 95% CI 0.11-0.73; p=0.011) and the slope of linear regression was significantly non-zero (1.23; 95% CI=0.68-1.77; p<0.0001). CONCLUSIONS HIFU ablation of liver tumours is safe and feasible. HIFU treatment is accurate, and intra-operative assessment of treatment provides an accurate measure of the zone of ablation and correlates well with MRI follow-up.

Endothelins & erectile dysfunction.

Erectile dysfunction (ED) is common and a significant contributor to poor quality of life and psychosocial morbidity in men. Normal erectile function requires effective co-ordination between a number of complex neural pathways. Penile tumescence occurs in response to rapid arterial inflow to the corpora cavernosa with simultaneous venous outflow restriction due to expansion of the lacunar spaces. This process is under both central and local neuromediation. Endothelins are potent vasoconstrictor peptides that cause strong, slowly developing but sustained contraction of trabecular smooth muscles cells of the corpora cavernosa. Multiple mechanisms of action are proposed, including transmembrane calcium flux, mobilisation of inositol triphosphate sensitive intracellular calcium stores and calcium sensitisation through the Rho-Rho kinase pathway. The exact role of endothelins in the pathogenesis of ED currently remains unclear. Elevated endothelin-1 levels are found in patients with diabetes mellitus and this alone may be sufficient to cause ED. However, this is not borne out in clinical studies. The resultant elevated intracellular calcium may, however, modulate gene expression sufficiently to cause smooth muscle proliferation. Alternatively, alterations in endothelin receptor sensitivity in conditions such as diabetes and hypertension may enhance vasoconstrictor processes. Currently there is contradictory evidence for the role of endothelin receptor antagonists in ED. Animals studies suggest they inhibit corporal vasoconstriction, improve erectile function and protect against diabetes-induced smooth muscle apoptosis. However, the results of clinical studies in ED have been less promising. Uncertainty regarding the exact role of endothelin in penile erection hampers progress in this area. It is possible that the endothelin system may only be relevant to ED in certain conditions where global endothelial dysfunction exists (e.g. diabetes mellitus, systemic sclerosis) and the use of endothelin antagonists in these patient groups may yield improved outcomes.

Laparoscopic high‐intensity focused ultrasound for renal tumours: a proof of concept study

Study Type – Therapy (case series)
Level of Evidence

Is Erectile Dysfunction an Example of Abnormal Endothelial Function

Erectile dysfunction (ED) affects approximately half of men during middle age. Erectile dysfunction is often an early symptom of systemic vascular disease, which may precipitate significant cardiac events. The pathophysiology of ED and cardiovascular disease is closely linked. Endothelial dysfunction occurs at an early stage in ED and cardiovascular disease (CVD). In normal conditions, nitric oxide dependent and independent mechanisms regulate penile vascular tone ensuring an appropriate balance of vasoconstriction and vasodilatation. A normal endothelium is responsible for mediating the effect of pro-erectile mediators derived from the endothelium and is critical in normal erectile function. Endothelial dysfunction disrupts the homeostatic mechanisms responsible for regulation of smooth muscle contraction and penile vascular tone. Reduced bioavailability of nitric oxide (NO) occurs as a response to endothelial damage. Phosphodiesterases further degrade levels of cyclic guanosine monophosphate (cGMP) and impair smooth muscle relaxation and erectile function. A number of endothelium derived NO independent mediators of erectile function have been described and are known to contribute to ED in the presence of endothelial damage. This review provides an up to date analysis of the role of the endothelium in ED describing the pathways involved and how these represent current and potential therapeutic targets.

HIGH INTENSITY FOCUSED ULTRASOUND ABLATION OF SMALL RENAL TUMOURS WITH AN EXTRA-CORPOREAL DEVICE: 3 YEAR OUTCOME DATA

INTRODUCTION AND OBJECTIVES: Surgery currently remains the gold standard treatment for localized renal cell carcinoma. Partial nephrectomy is indicated for T1a (<4cm) renal cancer. However, morbidity with partial nephrectomy approaches 20-25%. A variety of minimally invasive treatments have been proposed for small renal tumours; these include radiofrequency ablation, cryotherapy and high-intensity focused ultrasound (HIFU). HIFU results in ‘trackless’ homogenous tissue ablation and when administered via an extracorporeal device, is entirely non-invasive. METHODS: 17 patients (mean age 76 years; mean BMI 26 kgm2) with localised radiologically suspicious renal lesions <4cm maximum diameter were treated with extracorporeal HIFU using the Model-JC System (HAIFUTM). Mean tumour dimension was 3.5cm; 12/17 tumours were right sided. Real-time diagnostic ultrasound was used for targeting and monitoring; mean insonication time 21 minutes. Patients were followed with subtraction gandalinium-enhanced MRI at day 12 and six monthly. RESULTS: There were no major complications related to HIFU treatment. All patients were discharged within 24 hours. 14 patients completed six months radiological follow-up; two treatments were abandoned due to intervening bowel in the target field and were advised to undergo surgery. One patient underwent partial nephrectomy prior to six month follow-up as a result of a small area of residual enhancement. Radiological evidence of ablation was seen in seven out of 15 patients (47%) at day 12 imaging. Eight (53%) showed no clear radiological ablation at 12 days four underwent surgery at a mean of 11 months post HIFU and one underwent radiofrequency ablation 16 months after HIFU. Ten patients remain under surveillance at a mean of 36 months post treatment (range 24-51). The targeted lesion shows central loss of enhancement in all ten patients; a rim of peripheral enhancement was seen in all patients. Notably, there has been no increase in tumour dimension over the mean 3 year follow-up. CONCLUSIONS: This is the first medium term follow-up study of extracorporeal HIFU for renal cancer. 10 out of 15 (67%) patients have stable renal lesions at a mean of 3 years following treatment. However, half of patients showed no radiological evidence of ablation at 12 days and one third of all patients underwent alternative treatment modalities. Extracorporeal HIFU may yet have a role in the primary management of small renal cancers but the technique and treatment parameters need further refinement.

Significant skin burns may occur with the use of a water balloon in HIFU treatment

HIFU is a minimally-invasive therapy suitable for treating selected intra-abdominal tumors. Treatment is safe although skin burns may occur due to pre-focal heating. HIFU treatment of a renal transplant tumor located in the left lower abdomen was undertaken in our centre. Treatment was performed prone, requiring displacement of the abdominal wall away from the treatment field using a water balloon, constructed of natural rubber latex and filled with degassed water. Intra-operatively, ultrasound imaging and physical examination of the skin directly over the focal region was normal. Immediately post-operative, a full-thickness skin burn was evident at the periphery of the balloon location, outside the expected HIFU path. Three possibilities may account for this complication. Firstly, the water balloon may have acted as a lens, focusing the HIFU to a neo-focus off axis. Secondly, air bubbles may have been entrapped between the balloon and the skin, causing heating at the interface. Finally, heating of the is...

Passive mapping for imaging thermal lesions in tissue.

Passive acoustic mapping, a method of mapping sources of high‐frequency ultrasound emissions during focused ultrasound treatment, has been tested in ex vivo ox liver. The method uses an array of ultrasound sensors placed coaxially with a focused therapeutic ultrasound transducer. The ultrasound emissions received during treatment are first filtered and then beamformed to produce reconstructions of either broadband or harmonic source intensity within the tissue during the application of focused ultrasound. At pressure amplitudes in excess of the inertial cavitation threshold, passive mapping of broadband emissions is found to provide a good indication of the location and size of the lesion, while mapping of harmonic emissions adequately describes the location and onset of boiling. The results for different treatment parameters across several liver samples will be presented. Alternative methods of postprocessing the passively received data for improved spatiotemperoral resolution and signal‐to‐noise ratio w...