Salvage high-intensity focused ultrasound for locally recurrent prostate cancer after low-dose-rate brachytherapy: oncological and functional outcomes.

OBJECTIVES: To evaluate the oncological and functional outcomes of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after low-dose-rate (LDR) brachytherapy. PATIENTS AND METHODS: Clinical phase II studies (2003-2015) included 50 consecutive patients with post-brachytherapy local recurrence treated by S-HIFU. S-HIFU was performed with post-external beam radiotherapy (EBRT) parameters and, since 2008, with specific post-brachytherapy parameters. Treatments were whole-gland ablation and, since 2009, hemi-ablation in cases of unilateral prostate cancer. The primary objective was to assess oncological outcomes: treatment failure-free survival, progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) rates. The secondary objective was to evaluate adverse events, continence, and erectile function. Kaplan-Meier analysis estimated oncological outcomes. RESULTS: In all, 13 patients were treated with post-EBRT parameters, 37 with post-brachytherapy parameters, 35 with whole-gland treatment, and 15 with hemi-ablation. The median follow-up was 4.6 years. After S-HIFU, the median prostate-specific antigen level was 0.3 ng/mL. At 6 years, treatment failure-free survival, PFS, OS, CSS, and MFS rates were 41%, 45%, 93%, 98%, and 80%, respectively. Post-brachytherapy compared with post-EBRT parameters reduced Grade 2-3 incontinence (34% vs 62%, P = 0.015). Incontinence, bladder outlet obstruction and Grade ≥III complications were significantly reduced with hemi-ablation compared with whole-gland treatment (14% vs 54%, P < 0.001; 13% vs 46%, P = 0.03; 13% vs 63%, P = 0.001; respectively). Before S-HIFU, 25 patients had a five-item version of the International Index of Erectile Function score of ≥17, which was maintained in 48% at 12 months. CONCLUSION: S-HIFU for locally recurrent prostate cancer after LDR brachytherapy is associated with favourable survival rates at a price of significant morbidity. Dedicated post-brachytherapy parameters and hemi-ablation improve the safety of the treatment.

Brain palpation from physiological vibrations using MRI.

We present a magnetic resonance elastography approach for tissue characterization that is inspired by seismic noise correlation and time reversal. The idea consists of extracting the elasticity from the natural shear waves in living tissues that are caused by cardiac motion, blood pulsatility, and any muscle activity. In contrast to other magnetic resonance elastography techniques, this noise-based approach is, thus, passive and broadband and does not need any synchronization with sources. The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers. Potential applications of this "brain palpation" approach for characterizing brain anomalies and diseases are foreseen.

Prostate Focused Ultrasound Therapy.

The tremendous progress in engineering and computing power coupled with ultrasound transducer technology and imaging modalities over the past 20 years have encouraged a revival of clinical interest in ultrasound therapy, mainly in High-Intensity Focused Ultrasound (HIFU). So far, the most extensive results from HIFU obtained in urology involve transrectal prostate ablation, which appears to be an effective therapeutic alternative for patients with malignant prostate tumors. Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men. Several treatment options with different therapeutic approaches exist, including HIFU for localized PCa that has been in use for over 15 years. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. Two indications are validated today: Primary care treatment and EBRT failure. The results of HIFU for primary care treatment are similar to standard conformal EBRT, even though no randomized comparative studies have been performed and no 10-year follow up data is yet available for HIFU. Salvage HIFU after EBRT failure is increasing with oncological outcomes, similar to those achieved with surgery but with the advantage of fewer adverse effects. HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated.

Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radiorecurrent prostate cancer: a prospective two-centre study.

OBJECTIVE: To report the oncological and functional outcomes of hemi salvage high-intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer. PATIENTS AND METHODS: Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe. BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen [PSA] level). The following schemes and criteria for functional outcomes were used: Ingelman-Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function-5 (IIEF-5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction. RESULTS: After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5-24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6). CONCLUSION: HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health-related quality of life.

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.

A multi-element interstitial ultrasound applicator for the thermal therapy of brain tumors.

Interstitial thermal therapy is a minimally invasive treatment modality that has been used clinically for ablating both primary and secondary brain tumors. Here a multi-element interstitial ultrasound applicator is described that allows for increased spatial control during thermal ablation of tumors as compared to existing clinical devices. The device consists of an array of 56 ultrasound elements operating at 6 MHz, oriented on the seven faces of a 3.2 mm flexible catheter. The device was first characterized using the acoustic holography method to examine the functioning of the array. Then experiments were performed to measure heating in tissue-mimicking gel phantoms and ex vivo tissue samples using magnetic resonance imaging-based thermometry. Experimental measurements were compared with results obtained using numerical simulations. Last, simulations were performed to study the feasibility of using the device for thermal ablation in the brain. Experimental results show that the device can be used to induce a temperature rise of greater than 20 °C in ex vivo tissue samples and numerical simulations further demonstrate that tumors with diameters of greater than 30-mm could potentially be treated.

Dynamic Ultrasound Focusing and Centimeter-Scale Ex Vivo Tissue Ablations With a CMUT Probe Developed for Endocavitary HIFU Therapies.

Thermal ablation of localized prostate tumors via endocavitary ultrasound-guided high-intensity focused ultrasound (USgHIFU) faces challenges that could be alleviated by better integration of dual modalities (imaging/therapy). Capacitive micromachined ultrasound transducers (CMUTs) may provide an alternative to existing piezoelectric technologies by exhibiting advanced integration capability through miniaturization, broad frequency bandwidth, and potential for high electroacoustic efficiency. An endocavitary dual-mode USgHIFU probe was built to investigate the potential of using CMUT technologies for transrectal prostate cancer ablative therapy. The USgHIFU probe included a planar 64-element annular high-intensity focused ultrasound (HIFU) CMUT array ( [Formula: see text] = 3 MHz) surrounding a 256-element linear imaging CMUT array. Acoustic characterization of the HIFU array included 3-D pressure field mapping and radiation force balance measurements. Ex vivo proof-of-concept experiments consisted in generating HIFU thermal ablations with the CMUT probe on porcine liver tissues. The planar CMUT probe enabled HIFU dynamic focusing (distance range: 32-72 mm) while providing acoustic surface intensities of 1 W/cm2 that allowed producing elementary ex vivo ablations in depth of liver tissue ( L ×W ≈ 10×5 mm). Combinations of dynamic focusing, along with probe rotation and translation produced larger thermal ablations ( L ×W ≈ 20×20 mm) by juxtaposing multiple elementary ablations, consistent with expected results obtained through numerical modeling. The technical feasibility of using a USgHIFU probe, fully developed using CMUTs for tissue ablation purposes, was demonstrated. The HIFU-CMUT array showed tissue ablation capabilities with volumes compatible with localized cancer targeting, thus providing assets for further development of focal therapies.

Measurement of pulsatile motion with millisecond resolution by MRI.

We investigated a technique based on phase-contrast cine MRI combined with deconvolution of the phase shift waveforms to measure rapidly varying pulsatile motion waveforms. The technique does not require steady-state displacement during motion encoding. Simulations and experiments were performed in porcine liver samples in view of a specific application, namely the observation of transient displacements induced by acoustic radiation force. Simulations illustrate the advantages and shortcomings of the methods. For experimental validation, the waveforms were acquired with an ultrafast ultrasound scanner (Supersonic Imagine Aixplorer), and the rates of decay of the waveforms (relaxation time) were compared. With bipolar motion-encoding gradient of 8.4 ms, the method was able to measure displacement waveforms with a temporal resolution of 1 ms over a time course of 40 ms. Reasonable agreement was found between the rate of decay of the waveforms measured in ultrasound (2.8 ms) and in MRI (2.7-3.3 ms).

High-intensity focused ultrasound (HIFU)-assisted hepatic resection in an animal model.

BACKGROUND: Bleeding is the main cause of postoperative complications of hepatic surgery. To minimize intraoperative bleeding during hepatectomy, resections are generally carried out under hepatic vascular control despite the risk of liver dysfunction in patients with chronic liver disease. This study evaluates the feasibility and safety of high-intensity focused ultrasound (HIFU)-assisted hepatic resection during an open procedure in an animal model. METHODS: Three groups of 12-14-week-old Landrace pigs (n = 7/group) were used to evaluate HIFU-assisted liver resection (group A) vs liver resection with or without portal triad clamping (groups B and C). In each pig, liver resection was performed on the right and left paramedian lobes. The following were evaluated and compared in the 3 groups: total blood loss, blood loss/cm(2) of resection area, clip density, procedure duration, morbidity, and mortality. RESULTS: Median blood loss was significantly lower in group A than in group B (P = .02), and group C (P = .007). Median blood loss/cm(2) of resection area was 4.77 mL/cm² in group A, 11.35 mL/cm² in group B, 12.22 mL/cm² in Group C. Precoagulation resulted in sealing blood vessels <5 mm; therefore, median clip density during liver transection was 0.78 clip/cm² in group A, 1.61 clip/cm(2) in group B, and 1.57 clip/cm(2) in group C. Median duration of the surgical procedure was 12 min in group A, 21 min in group B, and 19 min in group C. CONCLUSIONS: HIFU-assisted hepatic resection during an open procedure in an animal model is safe, reduces bleeding, and allows real-time ultrasound guidance.

Neurostimulation success rate of repetitive-pulse focused ultrasound in an in vivo giant axon model: An acoustic parametric study.

PURPOSE: Focused ultrasound (FUS) is a promising tool to develop new modalities of therapeutic neurostimulation. The ability of FUS to stimulate the nervous system, in a noninvasive and spatiotemporally precise manner, has been demonstrated in animals and human subjects, but the underlying biomechanisms are not fully understood yet. The objective of the present study was to investigate the bioeffects involved in the generation of trains of action potentials (APs) by repetitive-pulse FUS stimuli in a simple invertebrate neural model. METHODS: The respective influences of different acoustic parameters on the neurostimulation success rate (NSR), defined as the rate of FUS stimuli capable of evoking at least one AP, were explored using the system of afferent nerves and giant fibers of Lumbricus terrestris as neural model. Each parameter was studied independently by administering random FUS sequences while keeping all but one FUS parameter constant. The NSR was evaluated as a function of (i) the spatial-average pulse-average intensity (Isapa ); (ii) the pulse duration (PD); (iii) the pulse repetition frequency (PRF); iv) the number of cycles per pulse (Ncycles ); (v) two ultrasound frequencies, f0  = 1.1 MHz and f3  = 3.3 MHz, corresponding to the fundamental and third-harmonic resonant frequencies of the FUS transducer, respectively (spherical, radius of curvature: 50 mm); and (vi) levels of emerging stable cavitation and inertial cavitation. RESULTS: The NSR associated to 1.1 MHz repetitive-pulse FUS stimuli was found to increase as a function of increasing Isapa , PD, PRF, and Ncycles . When evaluating each parameter at f = 1.1 MHz, it was observed that NSRs close to 100% were achieved when sufficiently elevating their respective values. When computing the NSR as a function of the spatial-average, temporal-average intensity (Isata ), defined as the product of PRF, PD, and Isapa , a significant elevation of the NSR from 0% to close to 100% was measured by increasing Isata from values approximate to 4 W/cm2 to values higher than 12 W/cm2 . No clear and consistent trend was observed in trials aimed at exploring the effects of different levels of stable and inertial acoustic cavitation on the NSR. Finally, the feasibility of inducing neural responses with 3.3 MHz repetitive-pulse FUS stimuli was also demonstrated with NSRs reaching up to 60%, in the range of FUS parameters studied. CONCLUSION: The time-averaged value of the radiation force per unit volume of tissue is proportional to the acoustic intensity. As a result, the observations from this study suggest that the neural structure responding to the stimulus is sensitive to the mean radiation force carried by the FUS sequence, regardless of the combination of FUS parameters giving rise to such force. The results from this study further revealed the existence of a minimal activation threshold with regard to Isapa .

Prostate cancer ablation with transrectal high-intensity focused ultrasound: assessment of tissue destruction with contrast-enhanced US.

PURPOSE: To assess contrast material-enhanced ultrasonographic (US) findings seen after high-intensity focused ultrasound (HIFU) ablation of prostate cancer and correlate the US findings with post-HIFU biopsy findings. MATERIALS AND METHODS: The study was ethics committee approved. Written informed consent was obtained from all patients. Twenty-eight patients referred for HIFU prostate cancer ablation underwent contrast-enhanced prostate US before treatment, gadolinium-enhanced magnetic resonance (MR) imaging and repeat contrast-enhanced US 1-3 days after treatment, and contrast-enhanced US-guided biopsy 30-45 days after treatment. The contrast-enhanced US enhancement patterns of the biopsy sites--assigned a score of S0 for no enhancement, S1 for mild and/or patchy enhancement, or S2 for marked enhancement--were compared with corresponding biopsy findings, which were assigned a score of B0 for necrosis and/or fibrosis without viable prostate gland tissue, B1 for vascularized tissue without viable gland tissue, or B2 for viable gland tissue (benign or malignant). Then, six additional patients underwent contrast-enhanced prostate US 15-30 minutes and 1 day after HIFU ablation, and the results of these two US examinations were compared. RESULTS: Contrast-enhanced US performed on days 1-3 and days 30-45 after HIFU ablation depicted a large devascularized zone with peripheral enhancing areas that were localized anteriorly in all 28 patients, posteriorly in nine, laterally in five, and at the apex in 20 patients. MR findings were concordant. At biopsy, viable gland tissue was found at nine (6.2%) of 146 S0 sites, 10 (34%) of 29 S1 sites, and 44 (60%) of 73 S2 sites. The odds ratios for finding viable tissue (score B1 or B2) at S1 and S2 sites as opposed to S0 sites were 21 (95% confidence interval [CI]: 6, 71) and 73 (95% CI: 22, 243), respectively (P < .0001). Contrast-enhanced US performed 15-30 minutes and 1 day after treatment in the six additional patients had similar findings. CONCLUSION: Contrast-enhanced US is a promising tool for distinguishing between ablated (devascularized) and viable (enhancing) tissue immediately after HIFU treatment.

Magnetic resonance elastography of the kidneys: feasibility and reproducibility in young healthy adults.

PURPOSE: To evaluate the feasibility and reproducibility of renal magnetic resonance elastography (MRE) in young healthy volunteers. MATERIALS AND METHODS: Ten volunteers underwent renal MRE twice at a 4-5 week interval. The vibrations (45 and 76 Hz) were generated by a speaker positioned beneath the volunteers' back and centered on their left kidney. For each frequency, three sagittal slices were acquired (eight phase offsets per cycle, motion-encoding gradients successively positioned along the three directions of space). Shear velocity images were reconstructed using the curl operator combined with the local frequency estimation (LFE) algorithm. RESULTS: The mean shear velocities measured in the renal parenchyma during the two examinations were not significantly different and exhibited a mean variation of 6% at 45 Hz and 76 Hz. The mean shear velocities in renal parenchyma were 2.21 ± 0.14 m/s at 45 Hz (shear modulus of 4.9 ± 0.5 kPa) and 3.07 ± 0.17 m/s at 76 Hz (9.4 ± 0.8 kPa, P < 0.01). The mean shear velocities in the renal cortex and medulla were respectively 2.19 ± 0.13 m/s and 2.32 ± 0.16 m/s at 45 Hz (P = 0.002) and 3.06 ± 0.16 m/s and 3.10 ± 0.22 m/s at 76 Hz (P = 0.13). CONCLUSION: Renal MRE was feasible and reproducible. Two independent measurements of shear velocities in the renal parenchyma of the same subjects showed an average variability of 6%.

Location of residual cancer after transrectal high-intensity focused ultrasound ablation for clinically localized prostate cancer.

UNLABELLED: What's known on the subject ? and What does the study add? Transrectal High-Intensity Focused Ultrasound (HIFU) ablation has been used as a minimally invasive treatment for localized prostate cancer for 15 years. Five-year disease-free survival rates of 66-78% have been reported, challenging the results of external-beam radiation therapy. Usually, a 6-mm safety margin is used in the apex to preserve the urinary sphincter and potency. The influence of this 6-mm margin on the results of the treatment has never been assessed. This retrospective study of a cohort of 99 patients who underwent systematic biopsy 3-6 months after HIFU ablation for prostate cancer (with a 6-mm safety margin in the apex) shows that post-HIFU residual cancer is found more frequently in the apex. Therefore, new strategies improving the prostate destruction at the apex while preserving the urinary continence need to be found. OBJECTIVE: • To evaluate whether the location (apex/midgland/base) of prostate cancer influences the risk of incomplete transrectal high-intensity focused ultrasonography (HIFU) ablation. PATIENTS AND METHODS: • We retrospectively studied 99 patients who underwent prostate cancer HIFU ablation (Ablatherm; EDAP, Vaulx-en-Velin, France) with a 6-mm safety margin at the apex, and had systematic biopsies 3-6 months after treatment. • Locations of positive pre- and post-HIFU sextants were compared. • The present study included two analyses. First, sextants negative before and positive after treatment were recoded as positive/positive, hypothesizing that cancer had been missed at pretreatment biopsy. Second, patients with such sextants were excluded. RESULTS: • Pre-HIFU biopsies found cancer in all patients and in 215/594 sextants (36.2%); 55 (25.6%) positive sextants were in the apex, 86 (40%) in the midgland and 74 (34.4%) in the base. • After treatment, residual cancer was found in 36 patients (36.4%) and 50 sextants (8.4%); 30 (60%) positive sextants were in the apex, 12 (24%) in the midgland and eight (16%) in the base. • Both statistical analyses found that the locations of the positive sextants before and after HIFU ablation were significantly different (P < 0.001), with a higher proportion of positive apical sextants after treatment. • At the first analysis, the mean (95% confidence interval) probability for a sextant to remain positive after HIFU ablation was 8.8% (3.5-20.3%) in the base, 12.7% (5.8-25.9%) in the midgland and 41.7% (27.2-57.89%) in the apex. • At the second analysis, these same probabilities were 5.9% (1.9-17%), 9.9% (3.9-23.2%) and 27.3% (13.7-47%), respectively. CONCLUSION: • When a 6-mm apical safety margin is used, residual cancer after HIFU ablation is found significantly more frequently in the apex.

Spatio-temporal characterization of causal electrophysiological activity stimulated by single pulse focused ultrasound: anex vivostudy on hippocampal brain slices.

Objective.The brain operates via generation, transmission and integration of neuronal signals and most neurological disorders are related to perturbation of these processes. Neurostimulation by focused ultrasound (FUS) is a promising technology with potential to rival other clinically used techniques for the investigation of brain function and treatment of numerous neurological diseases. The purpose of this study was to characterize spatial and temporal aspects of causal electrophysiological signals directly stimulated by short, single pulses of FUS onex vivomouse hippocampal brain slices.Approach.Microelectrode arrays (MEAs) are used to study the spatio-temporal dynamics of extracellular neuronal activities both at the single neuron and neural networks scales. Hence, MEAs provide an excellent platform for characterization of electrical activity generated, modulated and transmitted in response to FUS exposure. In this study, a novel mixed FUS/MEA platform was designed for the spatio-temporal description of the causal responses generated by single 1.78 MHz FUS pulses inex vivomouse hippocampal brain slices.Main results.Our results show that FUS pulses can generate local field potentials (LFPs), sustained by synchronized neuronal post-synaptic potentials, and reproducing network activities. LFPs induced by FUS stimulation were found to be repeatable to consecutive FUS pulses though exhibiting a wide range of amplitudes (50-600µV), durations (20-200 ms), and response delays (10-60 ms). Moreover, LFPs were spread across the hippocampal slice following single FUS pulses thus demonstrating that FUS may be capable of stimulating different neural structures within the hippocampus.Significance.Current knowledge on neurostimulation by ultrasound describes neuronal activity generated by trains of repetitive ultrasound pulses. This novel study details the causal neural responses produced by single-pulse FUS neurostimulation while illustrating the distribution and propagation properties of this neural activity along major neural pathways of the hippocampus.

Automatic temperature control for MR-guided interstitial ultrasound ablation in liver using a percutaneous applicator: ex vivo and in vivo initial studies.

Image-guided thermal ablation offers minimally invasive options for treating hepatocellular carcinoma and colorectal metastases in liver. Here, the feasibility and the potential benefit of active temperature control for MR-guided percutaneous ultrasound ablation was investigated in pig liver. An MR-compatible interstitial ultrasound applicator (flat transducer), a positioning system with rotation-translation guiding frame, and an orbital ring holder were developed. Step-by-step rotated elementary lesions were produced, each being formed by directive heating of a flame-shaped volume of tissue. In vivo feasibility of automatic temperature control was investigated on two pigs. Proton Resonance Frequency Shift (PRFS)-based MR thermometry was performed on a 1.5-T clinical scanner, using SENSE acceleration and respiratory gating. MR follow-up of animals and macroscopic analysis were performed at 3 and, respectively, 4 days postprocedure. No sonication-related radiofrequency artifacts were detected on MR images. The temperature controller converged to the target elevation within +/-2 degrees C unless the requested power level exceeded the authorized limit. Large variability of the controller's applied powers from one sonication to another was found both ex vivo and in vivo, indicating highly anisotropic acoustic coupling and/or tissue response to identical beam pattern along different radial directions. The automatic control of the temperature enabled reproducible shape of lesions (15 +/- 2 mm radial depth).

Prostate cancer transrectal HIFU ablation: detection of local recurrences using T2-weighted and dynamic contrast-enhanced MRI.

The objective was to evaluate T2-weighted (T2w) and dynamic contrast-enhanced (DCE) MRI in detecting local cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. Fifty-nine patients with biochemical recurrence after prostate HIFU ablation underwent T2-weighted and DCE MRI before transrectal biopsy. For each patient, biopsies were performed by two operators: operator 1 (blinded to MR results) performed random and colour Doppler-guided biopsies ("routine biopsies"); operator 2 obtained up to three cores per suspicious lesion on MRI ("targeted biopsies"). Seventy-seven suspicious lesions were detected on DCE images (n = 52), T2w images (n = 2) or both (n = 23). Forty patients and 41 MR lesions were positive at biopsy. Of the 36 remaining MR lesions, 20 contained viable benign glands. Targeted biopsy detected more cancers than routine biopsy (36 versus 27 patients, p = 0.0523). The mean percentages of positive cores per patient and of tumour invasion of the cores were significantly higher for targeted biopsies (p < 0.0001). The odds ratios of the probability of finding viable cancer and viable prostate tissue (benign or malignant) at targeted versus routine biopsy were respectively 3.35 (95% CI 3.05-3.64) and 1.38 (95% CI 1.13-1.63). MRI combining T2-weighted and DCE images is a promising method for guiding post-HIFU biopsy towards areas containing recurrent cancer and viable prostate tissue.

Evaluation of the Uncertainty of Passive Cavitation Measurements for Blood-Brain Barrier Disruption Monitoring.

Exposure to ultrasound combined with intravenous injection of microbubbles is a technique that can be used to temporarily disrupt the blood-brain barrier. Transcranial monitoring of cavitation can be done with one or more passive cavitation detectors (PCDs). However, the positioning of the PCDs relative to the cavitation site and the attenuation of these signals by the skull are two sources of error in the quantification of cavitation activity. The aim of this study was to evaluate in vitro the amplitude variation of cavitation signals that can be expected for an excised porcine skull model. The variation caused by the relative positioning of the PCD with respect to the cavitation site was quantified. A position-based correction of the signal amplitude was evaluated. Pig skull samples were used to assess variation in signal amplitude caused by bone. The overall coefficient of variation of the signals owing to these measurement biases was estimated at 30.8%.

Confocal lens focused piezoelectric lithotripter.

This work focuses on the evaluation of a type of piezoelectric lithotripter with similar dimensions of a commercial lithotripter and composed of either 3 or 4 large lens focused piezoelectric transducers set either in a confocal coplanar C-shape or a confocal spherical shape. Each transducer is made with a 92 mm diameter 220 kHz flat piezoelectric ceramic disc and a 3D printed acoustic lens. Both confocal setups pressure field were measured with a fiber optic hydrophone, and in vitro fragmentations of 13 mm diameter and 14 mm length cylindrical model stones were done in a 2 mm mesh basket. The acoustic characterization of the three transducers confocal setup revealed a disc shaped focal volume, with a 2.2 mm width on one axis and a 9.6 mm width on the other, and a peak positive pressure of 40.9 MPa and a peak negative pressure of -16.9 MPa, while the focus of the four transducers confocal setup was similar to a traditional narrow focus high pressure lithotripter with a focus width of 2.1 mm, and a peak positive pressure of 71.9 MPa and peak negative pressure of -24.3 MPa. Both confocal setups showed in vitro fragmentation efficiency close to a commercial electroconductive lithotripter.

High-intensity focused ultrasound ablation for the treatment of colorectal liver metastases during an open procedure: study on the pig.

OBJECTIVE: To demonstrate in a porcine model that high-intensity focused ultrasound (HIFU) with toroid-shaped emitters may have a role in treating unresectable colorectal liver metastases. SUMMARY BACKGROUND DATA: Surgical resection is the only curative option for colorectal hepatic metastases. Only 20% of patients are suitable for surgery. Many ablative techniques have been assessed but several limitations have been documented: traumatic puncture of the parenchyma, limited size of lesions, and inability to monitor the treatment in real time. METHODS: A HIFU device with 256 toroid-shaped emitters and integrated ultrasound imaging probe was used. Single lesions, induced in 40 seconds, and juxtaposition of 6 single lesions were created under ultrasound guidance on 13 pigs. The lesions were studied on sonograms, macroscopically and microscopically up to 30 days after the treatment. RESULTS: Ninety percent of the HIFU lesions were immediately hypoechoic on ultrasound imaging. The average coagulated volume obtained from a 40 seconds total exposure in the liver was 7.0 +/- 2.5 cm (1.5-20.0), average diameter: 19.5 +/- 3.8 mm (10.0-29.0). Using the real-time visualization of the treated region, single lesions were easily juxtaposed to produce larger lesions up to 6 cm in diameter without any major complication. CONCLUSIONS: This toroid HIFU device allows short treatment times, noninvasiveness regarding the liver and real time ultrasound guidance. It seems to be simpler and more reliable to use than current ablative methods. Additionally, lesions through large vessels (up to 5 mm) being feasible, treatment of some juxta-vascular metastases should be possible.

Experimental investigation of thermal effects in HIFU-based external valvuloplasty with a non-spherical transducer, using high-resolution MR thermometry.

Real-time image-guided extracorporeal high intensity focused ultrasound (HIFU) has been suggested for minimally invasive treatment of valvular dysfunction in the saphenous vein. Local application of heat on the perimeter of the valve zone was previously reported to induce a partial shrinkage of the collagen, which may correct valvular function. In our study, a novel MR compatible HIFU device has been investigated. This device is based on a non-spherical geometry, with two active elements that create a focusing line which is orthogonal to the beam main axis, aiming to cover the valve longitudinally. The prototype performance was characterized by electro-acoustical measurements of the pressure field and by high-resolution MR thermometry. Pressure and thermal fields were found in good agreement with the theoretical predictions. To investigate the therapeutic potential, fresh samples of excised human veins were filled with an agarose gel, embedded in porcine muscle and exposed to HIFU. The power level applied during a fixed duration of 30 s was varied such that the absolute temperature at focus ranged between 52 degrees C and 83 degrees C. Targeting was achieved under MR guidance using a MR compatible XZ positioning system. A dedicated waterproof miniature loop coil was specifically built to achieve high-resolution MRI image-based targeting (0.25 mm x 0.25 mm x 3 mm voxel) and thermometry (0.4 mm x 0.4 mm x 4 mm voxel). The vein wall was clearly identified on MR images before and after HIFU treatment. The thermal buildup created by the non-spherical transducer could be characterized from MR thermometry data. Shrinkage of the vein wall (above 65 degrees C) was determined by absolute temperature and was not a cumulative thermal dose effect.