High-intensity Focused Ultrasound Lesions Research Articles

Passive Elastography for Clinical HIFU Lesion Detection.

High-intensity Focused Ultrasound (HIFU) is a promising treatment modality for a wide range of pathologies including prostate cancer. However, the lack of a reliable ultrasound-based monitoring technique limits its clinical use. Ultrasound currently provides real-time HIFU planning, but its use for monitoring is usually limited to detecting the backscatter increase resulting from chaotic bubble appearance. HIFU has been shown to generate stiffening in various tissues, so elastography is an interesting lead for ablation monitoring. However, the standard techniques usually require the generation of a controlled push which can be problematic in deeper organs. Passive elastography offers a potential alternative as it uses the physiological wave field to estimate the elasticity in tissues and not an external perturbation. This technique was adapted to process B-mode images acquired with a clinical system. It was first shown to faithfully assess elasticity in calibrated phantoms. The technique was then implemented on the Focal One® clinical system to evaluate its capacity to detect HIFU lesions in vitro (CNR = 9.2 dB) showing its independence regarding the bubbles resulting from HIFU and in vivo where the physiological wave field was successfully used to detect and delineate lesions of different sizes in porcine liver. Finally, the technique was performed for the very first time in four prostate cancer patients showing strong variation in elasticity before and after HIFU treatment (average variation of 33.0 ± 16.0 % ). Passive elastography has shown evidence of its potential to monitor HIFU treatment and thus help spread its use.

In vivo exposure of the bladder using a non-invasive high intensity focused ultrasound toroidal transducer

A toroidal high-intensity focused ultrasound (HIFU) transducer was used to expose normal bladder wall tissues non-invasively in vivo in a porcine model in order to investigate the potential to treat bladder tumors. The transducer was divided into 32 concentric rings with equal surface areas, operating at 2.5 MHz. Eight animals were split into two groups of 4. In the first group, post-mortem evaluation was performed immediately after ultrasound exposure. In the second group, animals survived for up to seven days before post-mortem evaluation. The ultrasound imaging guided HIFU device was hand-held during the procedure using optical tracking to ensure correct targeting. One thermal lesion in each animal was created using a 40 s exposure at 80 acoustic Watts (free-field) in the trigone region of the bladder wall. The average (±Standard Deviation) abdominal wall and bladder wall thicknesses were 10.3 ± 1.4 mm and 1.1 ± 0.4 mm respectively. The longest and shortest axes of the HIFU ablations were 7.7 ± 2.9 mm and 6.0 ± 1.8 mm, respectively, resulting in an ablation of the whole thickness of the bladder wall in most cases. Ablation were performed at an average depth (distance from the skin surface to the centre of the HIFU lesion) of 42.5 ± 3.8 mm and extended throughout the thickness of the bladder. There were two cases of injury to tissues immediately adjacent to the bladder wall but without signs of perforation, as confirmed by histological analysis. Non-invasive HIFU ablation using a hand-held toroidal transducer was successfully performed to destroy regions of the bladder wall in vivo.

Reverse time migration and genetic algorithms Combined for Reconstruction in Transluminal Shear Wave Elastography: An In Silico Case Study

A new reconstruction approach that combines Reverse Time Migration (RTM) and Genetic Algorithms (GAs) is proposed for solving the inverse problem associated with transluminal shear wave elastography. The transurethral identification of the first thermal lesion generated by transrectal High Intensity Focused Ultrasound (HIFU) for the treatment of prostate cancer, was used to preliminarily test in silico the combined reconstruction method. The RTM method was optimised by comparing reconstruction images from several cross-correlation techniques, including a new proposed one, and different device configurations in terms of the number and arrangement of emitters and receivers of the conceptual transurethral probe. The best results were obtained for the new proposed cross-correlation method and a device configuration with 3 emitters and 32 receivers. The RTM reconstructions did not completely contour the shape of the HIFU lesion, however, as planned for the combined approach, the areas in the RTM images with high level of correlation were used to narrow down the search space in the GA-based technique. The GA-based technique was set to find the location of the HIFU lesion and the increment in stiffness and viscosity due to thermal damage. Overall, the combined approach achieves lower level of error in the reconstructed values, and in a shorter computational time, compared to the GA-based technique alone. The lowest errors were accomplished for the location of HIFU lesion, followed by the contrast ratio of stiffness between thermally treated tissue and non-treated normal tissue. The homologous ratio of viscosity obtained higher level of error. Further investigation considering diverse scenarios to be reconstructed and with experimental data is required to fully evaluate the feasibility of the combined approach.

Deep-Learning-Based High-Intensity Focused Ultrasound Lesion Segmentation in Multi-Wavelength Photoacoustic Imaging.

Photoacoustic (PA) imaging can be used to monitor high-intensity focused ultrasound (HIFU) therapies because ablation changes the optical absorption spectrum of the tissue, and this change can be detected with PA imaging. Multi-wavelength photoacoustic (MWPA) imaging makes this change easier to detect by repeating PA imaging at multiple optical wavelengths and sampling the optical absorption spectrum more thoroughly. Real-time pixel-wise classification in MWPA imaging can assist clinicians in monitoring HIFU lesion formation and will be a crucial milestone towards full HIFU therapy automation based on artificial intelligence. In this paper, we present a deep-learning-based approach to segment HIFU lesions in MWPA images. Ex vivo bovine tissue is ablated with HIFU and imaged via MWPA imaging. The acquired MWPA images are then used to train and test a convolutional neural network (CNN) for lesion segmentation. Traditional machine learning algorithms are also trained and tested to compare with the CNN, and the results show that the performance of the CNN significantly exceeds traditional machine learning algorithms. Feature selection is conducted to reduce the number of wavelengths to facilitate real-time implementation while retaining good segmentation performance. This study demonstrates the feasibility and high performance of the deep-learning-based lesion segmentation method in MWPA imaging to monitor HIFU lesion formation and the potential to implement this method in real time.

Ultrasound image segmentation using Gamma combined with Bayesian model for focused-ultrasound-surgery lesion recognition

This study aims to investigate the feasibility of combined segmentation for the separation of lesions from non-ablated regions, which allows surgeons to easily distinguish, measure, and evaluate the lesion area, thereby improving the quality of high-intensity focused-ultrasound (HIFU) surgery used for the non-invasive tumor treatment. Given that the flexible shape of the Gamma mixture model (GΓMM) fits the complex statistical distribution of samples, a method combining the GΓMM and Bayes framework is constructed for the classification of samples to obtain the segmentation result. An appropriate normalization range and parameters can be used to rapidly obtain a good performance of GΓMM segmentation. The performance values of the proposed method under four metrics (Dice score: 85%, Jaccard coefficient: 75%, recall: 86%, and accuracy: 96%) are better than those of conventional approaches including Otsu and Region growing. Furthermore, the statistical result of sample intensity indicates that the finding of the GΓMM is similar to that obtained by the manual method. These results indicate the stability and reliability of the GΓMM combined with the Bayes framework for the segmentation of HIFU lesions in ultrasound images. The experimental results show the possibility of combining the GΓMM with the Bayes framework to segment lesion areas and evaluate the effect of therapeutic ultrasound.

Non-invasive High-Intensity Focused Ultrasound Treatment of Liver Tissues in an In Vivo Porcine Model: Fast, Large and Safe Ablations Using a Toroidal Transducer.

A toroidal high-intensity focused ultrasound (HIFU) transducer was used to non-invasively treat liver tissues in vivo in a pig model. The transducer was divided into 32 concentric rings with equal surface areas operating at 2.5 MHz. First, attenuation of skin, fat, muscle and liver tissues was measured in fresh animal samples to adjust the energy delivered to the focal zone. Then, 8 animals were included in the present protocol and placed in a dorsal decubitus proclive position at an angle of 15°. The device was held by hand, and sonications were performed during apnea. Two thermal HIFU lesions were created in 40 s in each animal. The average abdominal wall thickness was 14.8 ± 1.3 mm (12.5-17.6 mm). The longest and shortest axes of the HIFU ablations were 20.9 ± 6.3 mm (14.0-33.7 mm) and 14.2 ± 5.5 mm (7.0-22.0 mm), respectively. All HIFU lesions were visible on sonograms. The correlation between the dimensions of the HIFU lesions observed on sonograms and those obtained during gross examination was r=0.84. Creating large and fast ablations with reliable ultrasound imaging guidance in the liver using this handheld device may represent a new therapeutic option for patients with liver tumors.

Detection of HIFU lesions by optical coherence tomography

The use of high-intensity focused ultrasound (HIFU) to induce irreversible changes in tissue due to heating is well established. We have shown that changes in tissue optical properties (scattering and absorption coefficients) could be used as a proxy to improve sensing and imaging of HIFU lesion formation, as an alternative to conventional methods such as thermometry. Optical coherence tomography (OCT) is a non-invasive optical imaging method which relies on low-coherence interferometry to determine the depth of individual scattering centres within the tissue. Previous studies have demonstrated that OCT signals are sensitive to morphological changes in heated tissue, likely due to denaturation of proteins concomitant with formation of crosslinked structures. The goal of this study was to assess the use of OCT for sensing and imaging HIFU lesions. We demonstrate the feasibility of imaging near-surface lesions in ex vivo chicken breast tissue exposed to HIFU. This technique has potential for detecting changes in optical properties corresponding to the progression of surface lesion formation which are antecedents of skin burn during HIFU exposures, thereby increasing safety and reducing treatment times.

Development of a noninvasive HIFU treatment for breast adenocarcinomas using a toroidal transducer based on preliminary attenuation measurements

Breast cancer is the most commonly diagnosed type of cancer among women. For the last fifteen years, treatments that are less invasive than lumpectomy, such as high-intensity focused ultrasound (HIFU) therapy, have been developed, with encouraging results. In this study, a toroidal HIFU transducer was used to create lesions of at least 2 cm in diameter within less than one minute of treatment. The toroidal HIFU transducer created two focal zones that led to large, fast and homogeneous ablations (10.5 cc/min). The experiments were conducted in 30 human samples of normal breast tissues recovered from mastectomies to measure acoustic attenuation (N = 30), and then, HIFU lesions were created (N = 15). Eight HIFU ablations were performed to evaluate the reproducibility of the lesions. HIFU lesions were created in 45 s with a toroidal HIFU transducer working at 2.5 MHz. The longest and shortest axes of the HIFU lesions were 21.7 ± 3.1 mm and 23.5 ± 3.3 mm respectively, corresponding to an average volume of 7.3 ± 1.4 cm3. These HIFU lesions were performed at an average depth of 19.0 ± 1.5 mm, while the integrity of the skin was preserved. The HIFU-treated breast tissues had a higher level of attenuation (0.57 ± 0.11 Np.cm−1.MHz−1) when compared to the untreated tissues (0.21 ± 0.04 Np.cm−1.MHz−1). This study shows the feasibility of a fast and fully noninvasive treatment using a toroidal transducer for breast tumors measuring up to 15 mm in diameter.

Evaluation of Ultrasonic Attenuation in Primary and Secondary Human Liver Tumors and Its Potential Effect on High-Intensity Focused Ultrasound Treatment

Primary and secondary liver tumors are completely different diseases but are usually treated similarly using high-intensity focused ultrasound (HIFU). However, the acoustic parameters of these tissues are not well documented. In this study, attenuation coefficients were evaluated in fresh primary (N = 8) and secondary (N = 13) human liver tumor samples recovered by hepatectomy. The average attenuation coefficients of the primary and secondary liver tumors were 0.10 ± 0.03 and 0.20 ± 0.04 Np/cm/MHz, respectively. The average attenuation coefficients of the liver tissue surrounding the primary and secondary tumors were 0.16 ± 0.07 and 0.07 ± 0.02 Np/cm/MHz, respectively. Numerical simulations performed using these values revealed that completely different HIFU ablation patterns were created in primary and secondary liver tumors using the same exposure parameters. The dimensions of a typical HIFU lesion were two times larger in secondary liver tumors than in primary tumors. HIFU treatment parameters should be set properly according to the acoustic properties of the diseased liver tissue.

Development of a Simple In Vitro Artery Model and an Evaluation of the Impact of Pulsed Flow on High-Intensity Focused Ultrasound Ablation

BackgroundMany parameters have to be investigated before an optimal strategy for thermal therapies can be defined. Such studies are limited by the number of animals that may be included and by the difficulties in the use of isolated perfused organs. Realistic in vitro anthropomorphic vascular phantoms have been suggested and are based on the use of agar or silicone but not on biological tissues. More simply, biological and reliable models can be developed to mimic the behavior of arteries under perfusion. Material and methodsChicken esophagus was used since it reproduces both the anatomical and the mechanical local properties of a 5-mm-diameter artery. The esophagus was placed inside a bovine liver and connected to polyurethane tubes. The flow was driven using two pumps and a solenoid to mimic pulsed flow and the cardiac valve. The blood was mimicked using degassed water and 50-μm silica beads at a concentration of 40 mg/L. The Doppler signals used as a reference to validate the in vitro artery model were acquired during an animal study. Using a high-intensity focused ultrasound (HIFU) device, several HIFU lesions were created in vitro in liver samples with the artery mimic model placed at different depths. ResultsThe waveforms of in vivo and in vitro Doppler signals had a cycle length of 1.09 s and 1.10 s, respectively, corresponding to 55 beats per minute (bpm). The average peak flow rate was 25.3 cm/s for in vivo waveforms and 27.8 cm/s for in vitro waveforms. The relative distension of the in vitro artery mimic (10%) was similar to that measured in pig mesenteric arteries and representative of human artery compliance. The dimensions of HIFU lesions were different depending on the location of the artery mimic. ConclusionsA simple and reliable model of arteries is described. This model reproduced both the geometrical and the mechanical local properties of an artery. The flow profile, the flow rate and compliant behavior were found to be similar to those that can be recorded in vivo. This model can be used to evaluate the potential perfusion effects when developing devices for thermal therapies.

Fast and Selective Ablation of Liver Tumors by High-Intensity Focused Ultrasound Using a Toroidal Transducer Guided by Ultrasound Imaging: The Results of Animal Experiments

This study demonstrated that high-intensity focused ultrasound (HIFU) produced with an intra-operative toroidal-shaped transducer causes fast, selective liver tumor ablations in an animal model. The HIFU device is composed of 256 emitters working at 3 MHz. A 7.5 MHz ultrasound imaging probe centered on the HIFU transducer guided treatment. VX2 tumor segments (25 mg) were implanted into the right lateral liver lobes of 45 New Zealand rabbits. The animals were evenly divided into groups 1 (toroidal HIFU ablation), 2 (surgical resection) and 3 (untreated control). Therapeutic responses were evaluated with gross pathology and histology 11 d post-treatment. Toroidal transducer-produced HIFU ablation (average ablation rate 10.5 cc/min) allowed fast and homogeneous tumor treatment. Sonograms showed all ablations. VX2 tumors were completely coagulated and surrounded by safety margins without surrounding-organ secondary HIFU lesions. HIFU group tumor volumes at autopsy (39 mm3) were significantly lower than control group volumes (2610 mm3, p < 0.0001). HIFU group tumor metastasis (27%) was lower than resected (33%) and control (67%) group metastasis. Ultrasound imaging, gross pathology and histology results supported these outcomes. HIFU procedures had no complications. Rabbit liver tumor ablation using a toroidal HIFU transducer under ultrasound imaging guidance might therefore be an effective intra-operative treatment for localized liver metastases.

High-Intensity Focused Ultrasound Using a Toroidal Transducer as an Adjuvant Treatment for Placenta Accreta: A Preliminary Ex Vivo Study

BackgroundPlacenta accreta is an abnormal invasion of the placenta within the myometrium, which has increasing rate and could result in maternal mortality or morbidity. The objective of this study was to evaluate the feasibility of treating placenta accreta with high-intensity focused ultrasound (HIFU) using an ex vivo model. Material and methodsA toroidal HIFU transducer working at 2.5 MHz with an integrated ultrasound-imaging probe was used. Ex vivo experiments were performed in eight human placentae (from 39 to 40 weeks) within a configuration that mimicked clinical conditions as closely as possible. The fetal side of the placenta was placed in contact with the sterile envelope that covered the HIFU device to simulate the uterine serosa. HIFU lesions were studied on sonograms and macroscopically. ResultsIn total, 19 single HIFU lesions were created with the same exposure parameters for all of the lesions. The exposure time was 75 s. The acoustic power was 90 W. HIFU lesions were created at different distances (2, 6, 7 and 8 mm) from the uterine serosa by adjusting the thickness of the coupling water and thus, the distance between the HIFU emitters and placental tissues. All of the lesions were homogeneous and approximately spherical in shape. The two diameters of the HIFU lesions were on average 14.6±2.1 mm and 14.1±2.3 mm. Lesions were immediately visible on sonograms after each HIFU exposure as a hyperechoic region. The distance between the surface of the placenta and HIFU lesion as measured on ultrasound images was closely correlated with the same distance that was measured on gross pathology (r=0.89, p<0.05). ConclusionsThis study demonstrates that HIFU may be an interesting option for adjuvant treatment during a cesarean of placenta accreta. These results must be validated under real clinical conditions.

HIFU tissue lesion quantification by optical coherence tomography

Heating of tissue by high-intensity focused ultrasound (HIFU) can result in sufficient temperature elevation to cause irreversible changes in the tissue structure. The contiguous volume occupied by these changes, a lesion, and the extent of the tissue changes may be quantified histologically or estimated through techniques such as ultrasonic elastography. We have shown that changes in tissue optical scattering could be used as a proxy to improve sensing and imaging of HIFU lesion formation as an alternative to thermometry. Optical coherence tomography (OCT) is a light-based method appropriate for optically accessible tissues, which we have used to quantify lesion volume, shape, and quality based upon the irreversible changes in optical scattering that occurs with protein denaturation. We have adapted OCT to take into account changes in optical polarization of the tissue, providing sensitivity to changes in the collagen orientation of skin with heating. This technique has potential in detecting antecedents of skin burn during HIFU exposures, thereby increasing safety and reducing treatment times.

High-frequency (20-MHz) high-intensity focused ultrasound (HIFU) system for dermal intervention: Preclinical evaluation in skin equivalents.

High-intensity focused ultrasound (HIFU) for non-invasive treatment of a range of internal pathologies including cancers of major organs and cerebral pathologies is in exponential growth. Systems, however, operate at relatively low frequencies, in the range of 200-2000kHz as required for deep axial penetration of the body. HIFU utilizing frequencies in excess of 15MHz has so far not been explored, but presents an opportunity to extend the HIFU modality to target specific dermal lesions and small animal research. A new 20-MHz HIFU system (TOOsonix ONE-R) with narrow focus corresponding to the dermis was studied in acoustic skin equivalents, for example, in a tissue-mimicking gel and in bovine liver. HIFU lesion geometry, depth, and diameter were determined. The temperature increase in the focal point was measured as a function of acoustic power and the duration of HIFU exposure. The system produces highly reproducible ultrasound lesions with predictable and configurable depths of 1-2mm, thus corresponding to the depth of the human dermis. The lesion geometry was elongated triangular and sized 0.1-0.5mm, convergent to a focal point skin deep. Focal point temperature ranged between 40 and 90°C depending on the chosen setting. Observations were confirmed ex vivo in bovine liver and porcine muscle. Variation of acoustic power and duration of exposure produced linear effects in the range of the settings studied. Thus, effects could be adjusted within the temperature interval and spatial field relevant for clinical therapy and experimental intervention targeting the dermal layer of human skin. The tested 20-MHz HIFU system for dermal applications fulfilled key prerequisite of narrow-field HIFU dedicated to cutaneous applications regarding reproducibility, geometry, and small size of the applied ultrasound lesions. Controlled adjustment of acoustic lesions within the temperature range 40-90°C qualifies the system for a range of non-ablative and ablative applications in dermatological therapy.

Noninvasive vascular occlusion with HIFU for venous insufficiency treatment: preclinical feasibility experience in rabbits

Venous insufficiency is a common disease arising when veins of the lower limb become incompetent. A conventional surgical strategy consists in stripping the incompetent veins. However, this treatment option is invasive and carries complication risks. In the present study, we propose noninvasive high-intensity focused ultrasound (HIFU) to treat lower limbs venous insufficiency, in particular incompetent perforating veins (mean diameter between 2–6 mm).Sonication parameters were designed by numerical simulations using the k-Wave toolbox to ensure continuous coagulation of a vein with a diameter superior or equal to 2 mm. The selected ultrasound exposures were 4 s pulses in continuous wave mode. Two types of sonication were studied: (1) fixed pulses and (2) moving pulses at constant speed (0.75 mm s−1) across the vein.The potential of these exposures to thermally occlude veins were investigated in vivo on rabbit saphenous veins. The impact of vein compression during ultrasonic exposure was also investigated.Fifteen rabbits were used in these trials. A total of 27 saphenous veins (mean diameter 2.0 ± 0.6 mm) were sonicated with a transducer operated at 3 MHz. After a mean 15 d follow-up, rabbits were euthanized and venous samples were extracted and sent for histologic assessment. Only samples with the vein within the HIFU lesion were considered for analysis.Simulated thermal damage distribution demonstrated that fixed pulses and moving pulses respectively placed every 1.5 and 0.5 mm along the vein and delivered at an acoustic power of 85 W and for 4 s were able to induce continuous thermal damages along the vein segments.Experimentally, both treatment parameters (1) and (2) have proven effective to occlude veins with a success rate of 82%. Occlusion was always observed when compression was applied.Our results demonstrate that HIFU can durably and non-invasively occlude veins of diameters comparable to human veins.

Detection of gaps between high-intensity focused ultrasound (HIFU)-induced lesions using transient axial shear strain elastograms.

High-intensity focused ultrasound (HIFU) is becoming an effective and noninvasive treatment modality for cancer and solid tumors. In order to avoid the cancer relapse and guarantee the success of ablation, there should be no gaps left among all HIFU-generated lesions. However, there are few imaging approaches available for detecting the HIFU lesion gaps in real time during ablation. Transient axial shear strain elastograms (ASSEs) were proposed and evaluated both numerically and experimentally to detect the lesion gaps immediately after the cessation of therapeutic HIFU exposure. Acoustic intensity and subsequent acoustic radiation force were first calculated by solving the nonlinear Khokhlov-Zabolotskaya-Kuznetzov (KZK) equation. Motion of being- and already-treated lesions during and after HIFU exposure was simulated using the transient dynamic analysis module of finite element method (FEM). The corresponding B-mode sonography of tissue-mimicking phantom with two HIFU lesions inside was simulated by FIELD II, and then axial strain elastograms (ASEs) under static compression and transient ASSEs were reconstructed. An ultrasound imaging probe was integrated with the HIFU transducer and used to obtain radio frequency (RF) echo signals at high frame rate using plane wave imaging (PWI). The resulting strains were mapped using the correlation-based method and block search strategy. Acoustic radiation force from the therapeutic HIFU burst is sufficiently strong to produce significant displacement. As a result, large and highly localized axial shear strain appears in the gap zone between two HIFU-generated lesions and then disappears after sufficient HIFU ablation (no gap between them). Such capability of detecting the lesion gap is validated at the varied acoustic radiation force density, gap width, and the size of the lesion. In contrast, conventional ASEs using the static compression cannot distinguish whether a gap exists between lesions. Static ASEs and transient ASSEs reconstructed using both high-speed photography and sonography in the gel phantom show the same conclusion as that in the simulation. Ex vivo tissue experiments further confirmed that the presence of large axial shear strain in the gap zone. The ratios of axial shear strain in the porcine kidney and liver samples had statistical differences for two HIFU-generated lesions without and with a gap (P < 0.05). Large axial shear strain induced by the acoustic radiation force from therapeutic HIFU burst only appears between two HIFU-generated lesions with a gap between them. Transient ASSEs reconstructed immediately after the cession of HIFU exposure can easily, reliably, and sensitively detect the gap between produced lesions, which would provide real-time feedback to enhance the success of HIFU ablation.

Experimental study of beam distortion due to fiducial markers during salvage HIFU in the prostate

BackgroundProstate cancer is frequently treated using external beam radiation therapy (EBRT). Prior to therapy, the prostate is commonly implanted with a small number of permanent fiducial markers used to monitor the position of the prostate during therapy. In the case of local cancer recurrence, high-intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option. However, the impact of the fiducial markers on HIFU treatment has not been thoroughly studied to date. The objective of this study was to experimentally investigate the effect of a single EBRT fiducial marker on the efficacy of HIFU treatment delivery using a tissue-mimicking material (TMM).MethodsA TMM with the acoustic properties of the prostate was developed based on a polyacrylamide hydrogel containing bovine serum albumin. Each phantom was implanted with a cylindrical fiducial marker and then sonicated using a 3.3 MHz focused bowl HIFU transducer. Two sets of experiments were performed. In the first, a single lesion was created at different positions along either the anteroposterior or left-right axes relative to the marker. In the second, a larger ablation volume was created by raster scanning. The size and position of the ablated volume were assessed using a millimetre grid overlaid on the phantom.ResultsThe impact of the marker on the position and size of the HIFU lesion was significant when the transducer focus was positioned within 7 mm anteriorly, 18 mm posteriorly or within 3 mm laterally of the marker. Beyond this, the generated lesion was not affected. When the focus was anterior to the marker, the lesion increased in size due to reflections. When the focus was posterior, the lesion decreased in size or was not present due to shadowing.ConclusionsThe presence of an EBRT fiducial marker may result in an undertreated region beyond the marker due to reduced energy arriving at the focus, and an overtreated region in front of the marker due to reflections. Depending on the position of the targeted regions and the distribution of the markers, both effects may be undesirable and reduce treatment efficacy. Further work is necessary to investigate whether these results indicate the necessity to reconsider patient selection and treatment planning for prostate salvage HIFU after failed EBRT.

Prostate cancer: transrectal high-intensity focused ultrasound for the treatment of local recurrence after radical prostatectomy or radiotherapy

OBJECTIVES. To evaluate the efficacy and safety of transrectal high-intensity focused ultrasound (HIFU) as salvage therapy for locally recurrent prostate cancer after external beam radiotherapy or recurrences located in the region of vesicourethral anastomosis after radical prostatectomy. METHODS. Transrectal biopsy of the prostate (recurrence after radiotherapy) or in the region of vesicourethral anastomosis (recurrence after prostatectomy) was performed in all cases at the time of biochemical relapse. Only patients with positive biopsy were treated. Systemic disease was excluded by PET-CT and bone scan. All treatments were carried out under spinal anesthesia. The device used was Ablatherm (EDAP, Lion, France). The patients were followed with PSA measurement every 3 months and clinical examination every 6 months. In case of biochemical relapse we performed re-biopsy. RESULTS. From 2002 to 2008 we treated 19 patients with local recurrence after radiotherapy. The mean follow-up was 30 months for each patient (range 6-72 months). 9 patients (47%) are disease-free at last followup, with PSA < 1 ng/mL. 9 patients experienced biochemical failure: 8 were treated with androgen deprivation, 1 with salvage prostatectomy. 2 patients died of the disease. Adverse events related to HIFU included 1 rectourethral fistula (observed before the use of specific parameters dedicated to this patient population) and mild incontinence (2-3 pads/die) in 4 patients. From 2002 to 2008 we treated 27 patients with a local recurrence after radical prostatectomy. Mean pre-HIFU PSA was 2.17 ng/mL (range 0.5-8 ng/ml); the Gleason score ranged from 5 to 8. All patients reached a minimum follow-up of 20 months (range 20-80 months). Median PSA nadir was 0.2 ng/ml. The disease-free rate was 51% (14/27); these patients have a median PSA of 0.2 ng/ml at last follow-up. 81% (22/27) of control biopsies were negative. There were no intra-operative or post-operative complications. CONCLUSIONS. The small number of patients in our series limits our ability to draw any definitive conclusions. We believe that HIFU may be a potentially useful treatment option for patients who develop prostate cancer recurrence after external beam radiotherapy or in the region of vesicourethral anastomosis after radical prostatectomy. The procedure is safe, side effects are acceptable and do not add significant morbidity to the previous radical treatment. HIFU lesions are targeted only to the area of recurrence. It is important to remember that, in case of failure, the patient can undertake any other therapies.

High-Intensity Focused Ultrasound Thermal Lesion Detection Using Entropy Imaging of Ultrasound Radio Frequency Signal Time Series.

Background:During the past few decades, high-intensity focused ultrasound (HIFU) modality has been gaining surging interest in various therapeutic applications such as non- or minimally-invasive cancer treatment. Among other attributes, robust and real-time HIFU treatment monitoring and lesion detection have become essential issues for successful clinical acceptance of the modality. More recently, ultrasound radio frequency (RF) time series imaging has been studied by a number of researchers.Materials and Methods:The objective of this study is to investigate the applicability of entropy parameter of RF time series of ultrasound backscattered signals, a. k. a. Entropy imaging, toward HIFU thermal lesion detection. To this end, five fresh ex vivo porcine muscle tissue samples were exposed to HIFU exposures with total acoustic powers ranging from 30 to 110 Watts. The contrast-to-speckle ratio (CSR) values of the entropy images and their corresponding B-mode images of pre-, during- and post-HIFU exposure for each acoustic power were calculated.Results:The novelty of this study is the use of Entropy parameter on ultrasound RF time series for the first time. Statistically significant differences were obtained between the CSR values for the B mode and entropy images at various acoustic powers. In case of 110 Watt, a CSR value 3.4 times higher than B-mode images was accomplished using the proposed method. Furthermore, the proposed method is compared with the scaling parameter of Nakagami imaging and same data which are used in this study.Conclusion:Entropy has the potential for using as an imaging parameter for differentiating lesions in HIFU surgery.

Integrated HIFU Drive System on a Chip for CMUT-Based Catheter Ablation System.

Conventional High Intensity Focused Ultrasound (HIFU) is a therapeutic modality which is extracorporeally administered. In applications where a relatively small HIFU lesion is required, an intravascular HIFU probe can be deployed to the ablation site. In this paper, we demonstrate the design and implementation a fully integrated HIFU drive system on a chip to be placed on a 6 Fr catheter probe. An 8-element capacitive micromachined ultrasound transducer (CMUT) ring array of 2 mm diameter has been used as the ultrasound source. The driver chip is fabricated in 0.35 μm AMS high-voltage CMOS technology and comprises eight continuous-wave (CW) high-voltage CMUT drivers (10.9 ns and 9.4ns rise and fall times at 20 V pp output into a 15 pF), an eight-channel digital beamformer (8-12 MHz output frequency with 11.25 ° phase accuracy) and a phase locked loop with an integrated VCO as a tunable clock source (128-192 MHz). The chip occupies 1.85 × 1.8 mm 2 area including input and output (I/O) pads. When the transducer array is immersed in sunflower oil and driven by the IC with eight 20 Vpp CW pulses at 10 MHz, real-time thermal images of the HIFU beam indicate that the focal temperature rises by 16.8 °C in 11 seconds. Each HV driver consumes around 67mW of power when driving the CMUT array at 10 MHz, which adds up to 560mW for the whole chip. FEM based analysis reveals that the outer surface temperature of the catheter is expected to remain below the 42 °C tissue damage limit during therapy.