The high power intensities in HTFU often result in bubble production, either through cavitation or boiling, which are believed to be a primary contributor to tissue necrosis Bubbles are associated with the appearance of bright hyperechoic regions in ultrasound B-mode images are observed from the bubbles. As they are often the only changes observed during treatment on tissue, some HIFU protocols rely on hyperechoicity as the indicator of tissue lesions. It would be useful clinically to keep a history of cavitation events during treatment which could be recalled on demand to assist planning. A reliable method of determining not just the presence of cavitation but its location is required for this. This paper introduces an active method of cavitation detection through analyzing spectrally the r.f. signal from an imaging transducer which interrogates the region on a pixel by pixel basis. Particular challenges are due to the limited bandwidth of the transducer and to provide good spatial and spectral resolution. Application to ex vivo pig liver using ARMA modeling on time series r.f. data shows that spectral information can be determined at a spatial resolution of about 1mm. The results of spectral estimation are used together with B-mode segmentation in a statistical algorithm to enhance the overall reliability of automatic cavitation detection. \u00a9 2007 IEEE.
\n \n\n \n \nOBJECTIVE: To propose a standard for the conduct of visually directed transrectal high-intensity focused ultrasound (HIFU) and to offer a formal description of the changes observed on B-mode ultrasonography (US) during this procedure. We describe our early experience of using two different treatment methods; algorithm-based HIFU and visually directed HIFU for the treatment of organ-confined prostate cancer. PATIENTS AND METHODS: Between November 2004 and October 2005, 34 men were treated using the Sonablate-500 (Focus Surgery, Indianapolis, IN, USA) as primary therapy for T1 or T2 prostate cancer. None had had previous hormone therapy and all had > or = 3-month PSA nadirs recorded at the follow-up. Nine men were treated using an algorithm-based protocol (group 1) and 25 using visually directed therapy (group 2). The conduct of visually directed treatment was described and changes seen using B-mode US were categorized using three 'Uchida' grades. RESULTS The mean PSA nadir achieved in group 2 was 0.15 ng/mL, vs 1.51 ng/mL in group 1 (P < 0.005). In group 2, 21 of 25 men achieved PSA nadirs of < or = 0.2 ng/mL 3 months after treatment. Seven men achieved undetectable PSA values. The occurrence rate of treatment-related toxicity was similar in both groups. CONCLUSION: Visually directed, transrectal HIFU enables clinically important and statistically significantly lower PSA nadirs to be achieved than algorithm-based HIFU. This is the first reported experience of visually directed HIFU for the treatment of organ-confined prostate cancer. We think that this is the first attempt to standardize the conduct of therapy; such standardization facilitates teaching it, and makes it possible to derive quality standards. The standardization of the conduct of therapy is a key step in the process of health technology assessment.
\n \n\n \n \nOBJECTIVE: To assess the extent of scrotal pain in men before and after vasectomy, to produce accurate data for the benefit of men considering this procedure, and hence improved informed consent about the outcomes, as chronic scrotal pain after vasectomy is a poorly quantified clinical problem. PATIENTS AND METHODS: Between November 2004 and January 2006 nine surgeons carried out vasectomies in 625 men (mean age 39.9 years, sd 5.6) under local anaesthesia. A questionnaire was devised to establish the presence of any scrotal or testicular pain, and to characterize this discomfort; 6 months after the procedure a modified version of the same questionnaire was administered. RESULTS: In all, 593 (94.7%) men returned the preoperative questionnaires and were entered into the study; 488 (82.2%) of these completed the follow-up questionnaire, giving a mean (sd) follow-up of 6.8 (1.6) months. In all, 65 men reported new-onset scrotal pain at 7 months (14.7%). The mean visual analogue score for this pain was 3.4/10. Four men (0.9%) in the responding group described pain after vasectomy as 'quite severe and noticeably affecting their quality of life'. CONCLUSION: At 7 months after vasectomy about 15% of previously asymptomatic men have some degree of scrotal discomfort. These early data indicate that chronic scrotal pain after vasectomy is a genuine entity, but a longer-term follow-up in this group will be important to allow further evaluation of how this pain develops with time.
\n \n\n \n \nHigh-intensity focused ultrasound (HIFU) continues to be a very attractive option for minimally invasive procedures. Using well-established principles, this ablative therapy can be used to treat a number of benign and malignant diseases with few side effects. During the last 15 years, there has been an enormous amount of work, both laboratory based and in the form of clinical trials, aimed at developing devices that can deliver treatments with safe and effective outcomes. In this article, we aim to outline the principles of HIFU, describe the current commercially available machines and their applications, and discuss the role of HIFU in the future.
\n \n\n \n \nRenal cell carcinomas (RCCs) account for 3% of all solid neoplasms, with an increased incidence after renal transplantation. In transplant recipients, RCCs predominantly occur in the patient's native kidneys. Herein is reported a case of a localized RCC of recipient origin that developed in the donor allograft and was detected 8 years after renal transplantation. Treatment with high-intensity focussed ultrasound followed by partial nephrectomy was successful, averting the need for dialysis therapy.
\n \n\n \n \nThe aim of this study was to investigate the use of time to maximum enhancement (t(max)) for each voxel in contrast-enhanced MRI (CE-MRI) as a non-invasive tool to determine areas of necrosis following treatment of liver tumours with high-intensity focused ultrasound (HIFU) and, having established the utility of t(max) maps, to develop a three-dimensional (3-D) representation to display this information concisely. 3-D T(1) weighted fast spoiled gradient echo images of the liver were acquired before and after administration of contrast agent. The CE-MR images were aligned to the pre-contrast volume and an estimate of t(max) was obtained for each voxel. Such pre- and post-contrast image sets were acquired before and after ablation. The t(max) maps before and after HIFU treatment were correlated with the procedure notes, radiological reports and gross histological specimen. Finally, 3-D t(max) maps of the whole liver were reconstructed to show all areas of abnormal tissue perfusion. Normal, healthy liver tissue uniformly enhances maximally after approximately 1 min. The computed t(max) maps accurately delineated areas of abnormal contrast agent uptake, corresponding to tumour deposits. Changes in t(max) and non-enhancing voxels after treatment correlate well with volumes targeted during ablation and the necrotic regions seen on gross histological specimens. Alignment of the contrast-enhanced images with the pre-contrast volume greatly improved the conspicuity of the t(max) maps. We conclude that t(max) maps and their 3-D views can be used as a non-invasive tool to assess and potentially to quantify the success of HIFU ablation, and concisely represent the large number of CE-MRI data.
\n \n\n \n \nUNLABELLED: Study Type--Therapy (case series) Level of Evidence What's known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib-cage limiting energy delivery. For this study, a purpose-built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications. OBJECTIVE: \u2022 To test and establish clinical proof of concept for a laparoscopic high-intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface. PATIENTS AND METHODS: \u2022 \u2002 Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18-mm laparoscopic port. \u2022 HIFU treatment was targeted at a pre-defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed. RESULTS: \u2022 No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients. \u2022 The ablated zones were within the targeted area in all patients and no intra-lesional skipping was seen. \u2022 Subcapsular skipping was seen at the probe-tumour interface in two patients with viable tumour cells seen at microscopy. \u2022 One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells. \u2022 There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow-up of 15 (8-24) months with no evidence of metastatic disease or late complications. CONCLUSIONS: \u2022 Tumour ablation with laparoscopic HIFU is feasible. \u2022 Homogenous ablation can be achieved with no vital tissue within the targeted zone. \u2022 The technique is associated with low morbidity and may have a role in the definitive management of small tumours.
\n \n\n \n \nIn recent years high intensity focused ultrasound (HIFU) has received increasing interest as a non-invasive modality for the treatment of tumours of solid organs. Surgeons continue their quest to find the optimal technique whereby a diseased organ can be treated with a minimum of damage to the patient, while providing a comprehensive treatment to produce either cure or resolution of symptoms. Two of the areas in which HIFU is beginning to establish itself as a real therapeutic alternative, are in the treatment of abdominal and gynaecological disease. In this paper, we will review the literature available regarding the use of HIFU in the treatment of various organs: liver, kidney, pancreas, bladder, uterus and vulva.
\n \n\n \n \nPURPOSE: 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.
\n \n\n \n \nA major thrust in brain machine interface (BMI) is to establish a robust, bi-directional direct link between the central nervous system (CNS) and artificial devices (e.g. medical implants, artificial organs, neural stimulators, robotic hands, etc.) for cybernetic interface and treatment of a range of neurodegenerative conditions. Significant effort has centered on support of motor control through external devices and direct stimulation through implanted electrodes in the brain, ideally supporting paralyzed or neurally damaged patients by bypassing damaged regions of the brain. The majority of neural decoding studies have focused on cortical areas for BMIs; however deep brain structures have also been involved in motor control. The subthalamic nucleus (STN) in the basal ganglia, for example, is involved in the preparation, execution and imagining of movements, and represents an unexplored alternative source with great potential for driving BMIs. The goal of this study is to establish this potential through decoding of deep brain local field potentials (LFPs) related to movement execution and laterality of visually cued movements. LFPs were recorded bilaterally from the STN through deep brain stimulation electrodes surgically implanted in patients with Parkinson's disease. The frequency dependent components of the LFPs were extracted using the wavelet packet transform. In each frequency component, signal features were extracted as the instantaneous power computed using the Hilbert transform. Based on these extracted features, a new feature selection strategy was developed to efficiently select the optimal feature subset. Two classifiers, the Bayesian and support vector machine (SVM) were implemented alongside this novel feature selection strategy, and evaluated using a cross-validation procedure. With optimised feature subset, average correct decoding of movement achieved 99.6\u00b10.2% and 99.8\u00b10.2% and subsequent laterality (left or right) classification reached 77.9\u00b12.7% and 82.7\u00b12.8% using the Bayesian and SVM classifier respectively. The work suggests that the neural activity in the basal ganglia can be used for controlling BMIs and holds great promise for a future generation of interfaces based in the STN. \u00a9 2012 IEEE.
\n \n\n \n \nThe neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70 of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (13). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli. \u00a9 2012 The Author. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
\n \n\n \n \nDeep brain stimulation (DBS) is an expanding field in neurosurgery and has already provided important insights into the fundamental mechanisms underlying brain function. One of the most exciting emerging applications of DBS is modulation of blood pressure, respiration and micturition through its effects on the autonomic nervous system. DBS stimulation at various sites in the central autonomic network produces rapid changes in the functioning of specific organs and physiological systems that are distinct from its therapeutic effects on central nervous motor and sensory systems. For example, DBS modulates several parameters of cardiovascular function, including heart rate, blood pressure, heart rate variability, baroreceptor sensitivity and blood pressure variability. The beneficial effects of DBS also extend to improvements in lung function. This article includes an overview of the anatomy of the central autonomic network, which consists of autonomic nervous system components in the cortex, diencephalon and brainstem that project to the spinal cord or cranial nerves. The effects of DBS on physiological functioning (particularly of the cardiovascular and respiratory systems) are discussed, and the potential for these findings to be translated into therapies for patients with autonomic diseases is examined. \u00a9 2012 Macmillan Publishers Limited.
\n \n\n \n \nThis paper explores the development of multi-feature classification techniques used to identify tremor-related characteristics in the Parkinsonian patient. Local field potentials were recorded from the subthalamic nucleus and the globus pallidus internus of eight Parkinsonian patients through the implanted electrodes of a Deep brain stimulation (DBS) device prior to device internalization. A range of signal processing techniques were evaluated with respect to their tremor detection capability and used as inputs in a multi-feature neural network classifier to identify the activity of Parkinsonian tremor. The results of this study show that a trained multi-feature neural network is able, under certain conditions, to achieve excellent detection accuracy on patients unseen during training. Overall the tremor detection accuracy was mixed, although an accuracy of over 86% was achieved in four out of the eight patients.
\n \n\n \n \nDeep Brain Stimulation has been used in the study of and for treating Parkinson's Disease (PD) tremor symptoms since the 1980s. In the research reported here we have carried out a comparative analysis to classify tremor onset based on intraoperative microelectrode recordings of a PD patient's brain Local Field Potential (LFP) signals. In particular, we compared the performance of a Support Vector Machine (SVM) with two well known artificial neural network classifiers, namely a Multiple Layer Perceptron (MLP) and a Radial Basis Function Network (RBN). The results show that in this study, using specifically PD data, the SVM provided an overall better classification rate achieving an accuracy of 81% recognition. \u00a9 2012 Elsevier Ltd. All rights reserved.
\n \n\n \n \nDeep brain stimulation (DBS) has been shown to be clinically effective for some forms of treatment-resistant chronic pain, but the precise mechanisms of action are not well understood. Here, we present an analysis of magnetoencephalography (MEG) data from a patient with whole-body chronic pain, in order to investigate changes in neural activity induced by DBS for pain relief over both short- and long-term. This patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). We demonstrate that a novel method, null-beamforming, can be used to localise accurately brain activity despite the artefacts caused by the presence of DBS electrodes and stimulus pulses. The accuracy of our source localisation was verified by correlating the predicted DBS electrode positions with their actual positions. Using this beamforming method, we examined changes in whole-brain activity comparing pain relief achieved with deep brain stimulation (DBS ON) and compared with pain experienced with no stimulation (DBS OFF). We found significant changes in activity in pain-related regions including the pre-supplementary motor area, brainstem (periaqueductal gray) and dissociable parts of caudal and rostral ACC. In particular, when the patient reported experiencing pain, there was increased activity in different regions of ACC compared to when he experienced pain relief. We were also able to demonstrate long-term functional brain changes as a result of continuous DBS over one year, leading to specific changes in the activity in dissociable regions of caudal and rostral ACC. These results broaden our understanding of the underlying mechanisms of DBS in the human brain.
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