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Introduction Endovenous techniques such as ultrasound guided foam sclerotherapy, thermal methods, or glues are generally recommended to occlude incompetent veins. However, these methods can be technically challenging and risky for patients with severe atrophic skin disorders like lipodermatosclerosis or atrophie blanche. High intensity focused ultrasound (HIFU), which has been shown to coagulate and occlude veins successfully, may offer an alternative method. This case report details ultrasound guided HIFU to occlude non-invasively a refluxing perforator vein causing active ulcers. Report A 95 year old man presented to the Institute for Functional Phlebology (Melk, Austria) with painful recurrent ulcers in his left medial calf. His limb was scored C2,3,4a, b,6, Ep, Ap, Pr,18 according to the Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification. Lower limb ultrasound revealed a refluxing posterior tibial perforating vein, measuring 2.7 mm in diameter at the level of the fascia. Extracorporeal HIFU pulses were delivered to this vein with the Sonovein device (Theraclion, Malakoff, France). Sonication was applied for eight seconds at a mean acoustic power of 80 W. The patient was followed up for three months post-treatment and occlusion was evaluated by duplex ultrasound. There were no complications during treatment or follow up. Three months after the treatment, reflux was abolished and the two initially active ulcers had healed. Discussion Although this is an early report, this study shows that HIFU can be successful in ablation of incompetent perforator veins in the treatment of venous leg ulcers., Highlights • Endovenous methods are not suited to all patients with severe skin disorders. • High intensity focused ultrasound can treat venous leg disorders non-invasively. • Treatments have been performed on a refluxing perforator vein causing active ulcers. • Short-term results showed that this technique is as good as other thermal therapies.

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.

Ultrasound-enhanced drug delivery has shown great promise in providing targeted burst release of drug at the site of the disease. Yet current solid ultrasound-responsive particles are non-degradable with limited potential for drug-loading. Here, we report on an ultrasound-responsive multi-cavity poly(lactic-co-glycolic acid) microparticle (mcPLGA MP) loaded with rhodamine B (RhB) with or without 4′,6-diamidino-2-phenylindole (DAPI) to represent small molecule therapeutics. After exposure to high intensity focused ultrasound (HIFU), these delivery vehicles were remotely implanted into gel and porcine tissue models, where the particles rapidly released their payload within the frst day and sustained release for at least seven days. RhB-mcPLGA MPs were implanted with HIFU into and beyond the sub-endothelial space of porcine arteries without observable damage to the artery. HIFU also guided the location of implantation; RhB-mcPLGA MPs were only observed at the focus of the HIFU away from the direction of ultrasound. Once implanted, DAPI co-loaded RhB-mcPLGA MPs released DAPI into the arterial wall, staining the nucleus of the cells. Our work shows the potential for HIFUguided implantation of drug-loaded particles as a strategy to improve the local and sustained delivery of a therapeutic for up to two weeks. NMRC (Natl Medical Research Council, S’pore) Published version

One of the great advancements in the applications of piezoelectric materials is the application for therapeutic medical ultrasound for sonothrombolysis. Sonothrombolysis is a promising ultrasound based technique to treat blood clots compared to conventional thrombolytic treatments or mechanical thrombectomy. Recent clinical trials using transcranial Doppler ultrasound, microbubble mediated sonothrombolysis, and catheter directed sonothrombolysis have shown promise. However, these conventional sonothrombolysis techniques still pose clinical safety limitations, preventing their application for standard of care. Recent advances in sonothrombolysis techniques including targeted and drug loaded microbubbles, phase change nanodroplets, high intensity focused ultrasound, histotripsy, and improved intravascular transducers, address some of the limitations of conventional sonothrombolysis treatments. Here, we review the strengths and limitations of these latest pre-clincial advancements for sonothrombolysis and their potential to improve clinical blood clot treatments.

Ultrasound can penetrate deep into tissues and interact with human tissue via thermal and mechanical mechanisms. The ability to focus an ultrasound beam and its energy onto millimeter-size targets was a significant milestone in the development of therapeutic applications of focused ultrasound. Focused ultrasound can be used as a non-invasive thermal ablation technique for tumor treatment and is being developed as an option to standard oncologic therapies. High-intensity focused ultrasound has now been used for clinical treatment of a variety of solid malignant tumors, including those in the pancreas, liver, kidney, bone, prostate, and breast, as well as uterine fibroids and soft-tissue sarcomas. Magnetic resonance imaging and Ultrasound imaging can be combined with high intensity focused ultrasound to provide real-time imaging during ablation. Magnetic resonance guided focused ultrasound represents a novel non-invasive method of treatment that may play an important role as an alternative to open neurosurgical procedures for treatment of a number of brain disorders. This paper briefly reviews the underlying principles of HIFU and presents current applications, outcomes, and complications after treatment. Recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed, along with clinical challenges and potential future clinical applications of HIFU.

Mesenchymal stromal cell (MSC) therapies combined with renal pulsed focused ultrasound (pFUS) pretreatment increase MSC homing and improve cisplatin‐induced acute kidney injury (AKI) better than MSC alone. However, mechanisms underlying improved outcomes remain unknown. We hypothesize pFUS up‐regulates renal interferon‐γ (IFNγ) and stimulates MSC to produce interleukin‐10 (IL‐10) after migrating to kidneys. To demonstrate initially, MSC cultured with IFNγ up‐regulated IL‐10. More MSC‐derived IL‐10 was detected in kidneys when IFNγ‐stimulated MSC were infused and they improved AKI better than unstimulated MSC. Next, IFNγ‐knockout mice with AKI received pFUS+MSC, but MSC‐derived IL‐10 expression and AKI were similar to using MSC alone. AKI in wild‐type mice receiving pFUS and IL‐10‐deficient MSC was also unimproved compared to administering IL‐10‐deficient MSC alone. Indoleamine 2,3‐dioxygenase (IDO), an anti‐inflammatory enzyme up‐regulated in MSC by IFNγ, was up‐regulated during AKI, but was not further elevated in MSC from pFUS‐treated kidneys, suggesting that IDO is not involved in improved AKI healing by pFUS+MSC. These data suggest IFNγ is up‐regulated by pFUS and after i.v.‐infused MSC home to pFUS‐treated kidneys, IFNγ stimulates additional IL‐10 production by MSC to improve AKI. Analogous mechanisms of ultrasound‐treated tissue microenvironments stimulating therapeutic MSC may exist in other pathologies where adjuvant ultrasound techniques are successful.

High intensity focused ultrasound (HIFU) has gained clinical interest as a non-invasive local tumour therapy in many organs. In addition, it has been shown that lung cancer can be targeted by HIFU using One-Lung Flooding (OLF). OLF generates a gas free saline-lung compound in one lung wing and therefore acoustic access to central lung tumours. It can be assumed that lung parenchyma is exposed to ultrasound intensities in the pre-focal path and in cases of misguiding. If so, cavitation might be induced in the saline fraction of flooded lung and cause tissue damage. Therefore this study was aimed to determine the thresholds of HIFU induced cavitation and tissue erosion in flooded lung. Resected human lung lobes were flooded ex-vivo. HIFU (1,1 MHz) was targeted under sonographic guidance into flooded lung parenchyma. Cavitation events were counted using subharmonic passive cavitation detection (PCD). B-Mode imaging was used to detect cavitation and erosion sonographically. Tissue samples out of the focal zone were analysed histologically. In flooded lung, a PCD and a sonographic cavitation detection threshold of 625 Wcm − 2(p r = 4, 3 MPa) and 3.600 Wcm − 2(p r = 8, 3 MPa) was found. Cavitation in flooded lung appears as blurred hyperechoic focal region, which enhances echogenity with insonation time. Lung parenchyma erosion was detected at intensities above 7.200 Wcm − 2(p r = 10, 9 MPa). Cavitation occurs in flooded lung parenchyma, which can be detected passively and by B-Mode imaging. Focal intensities required for lung tumour ablation are below levels where erosive events occur. Therefore focal cavitation events can be monitored and potential risk from tissue erosion in flooded lung avoided.

International audience; Transcranial brain therapy has recently emerged as a non-invasive strategy for the treatment of various neurological diseases, such as essential tremor or neurogenic pain. However, treatments require millimetre-scale accuracy. The use of high frequencies (typically ≥1 MHz) decreases the ultrasonic wavelength to the millimetre scale, thereby increasing the clinical accuracy and lowering the probability of cavitation, which improves the safety of the technique compared with the use of low-frequency devices that operate at 220 kHz. Nevertheless, the skull produces greater distortions of high-frequency waves relative to low-frequency waves. High-frequency waves require high-performance adaptive focusing techniques, based on modelling the wave propagation through the skull. This study sought to optimise the acoustical modelling of the skull based on computed tomography (CT) for a 1 MHz clinical brain therapy system. The best model tested in this article corresponded to a maximum speed of sound of 4000 m.s-1 in the skull bone, and it restored 86% of the optimal pressure amplitude on average in a collection of six human skulls. Compared with uncorrected focusing, the optimised non-invasive correction led to an average increase of 99% in the maximum pressure amplitude around the target and an average decrease of 48% in the distance between the peak pressure and the selected target. The attenuation through the skulls was also assessed within the bandwidth of the transducers, and it was found to vary in the range of 10 ± 3 dB at 800 kHz and 16 ± 3 dB at 1.3 MHz.

A major challenge in chemotherapy is that the systemic delivery of drugs to both healthy tissue as well as the tumour results in unwanted side effects. Thermosensitive liposomal carriers are designed to release their payload when they are exposed to mild hyperthermia (a few degrees above body temperature). If a tumour can be locally heated, thermosensitive liposomes can provide triggered and localised delivery of the drug which should reduce systemic toxicity. Ultrasound is a noninvasive modality which can be used to produce localised heating at depth. However, most clinically approved high-intensity focused ultrasound (HIFU) systems are designed for tumour ablation and exhibit a focal volume which typically spans 1-3mm in width and 10-15mm in length, generating temperatures in excess of 50◦C for a few seconds to directly kill tissue within the focal volume. Hyperthermia-triggered drug release usually requires maintaining a tumour volume which often spans several centimetres in size at a consistent therapeutic temperature of 39.5-42◦C for durations up to an hour. This is difficult to achieve for most current HIFU transducers due to their small focal volume. The approach employed here is to design an acoustic lens that retrofits onto a clinical HIFU system to produce a focal volume better suited for mild hyperthermia. 3D printing is employed in this work to produce the lenses, and sectored lenses which enable a single-element transducer to produce acoustic fields with multiple foci in an annular pattern are investigated. Experimental measurements of the pressure and temperature using a small therapeutic transducer are consistent with simulations, and the simulated -3dB free-field focal volume of the transducer was increased from 9.6mm3 to 90.9mm3. Finite element software is used to perform 3D linear full-wave simulations of an acoustic lens in a human liver target derived from a segmented CT dataset. The computational challenges with performing large 3D finite element simulations are addressed by dividing the simulation domain into several subregions. A phase-conjugate lens combined with masking transducer locations associated with ribs is explored as a solution to address aberrations in the acoustic field caused by tissue inhomogeneity. Experiments with a sectored acoustic lens on a clinical HIFU system showed the radial location of the free-field focus was shifted from 0mm to ±2.8mm in an annular pattern. This work shows that retrofitting a HIFU system with an acoustic lens is a practical approach to broadening the focal spot.

Effect of high intensity focused ultrasound (HIFU) uterine fibroid ablation on the endometrial receptivity and sex hormone level in uterine fibroid patients and the influencing factors for treatment rate were investigated. A retrospective analysis of 266 uterine fibroid patients admitted to the Department of Gynaecology in the Jining Maternity and Child Care Hospital from October 2013 to October 2016 was performed. Among them, observation group was treated with HIFU ablation (n=143), control group with myomectomy (n=123). The pulsatility index (PI) and the resistance index (RI) of the uterine arterial blood flow were measured during the luteal phase of menstruation by transvaginal ultrasonography. The serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were detected by chemical immunofluorescence. The relationship between HIFU treatment rate and clinical pathology of uterine fibroid patients was analyzed, and univariate/multivariate regression analysis was used to analyze the influencing factors for HIFU treatment rate. There was no significant difference in preoperative and postoperative PI and RI between the two groups (P>0.05); no significant difference between preoperative and postoperative PI/RI in the same group (P>0.05). There was no significant difference in preoperative and postoperative LH, FSH and E2 between the two groups (P>0.05); no significant difference between preoperative LH and postoperative LH in the same group (P>0.05), neither FSH or E2 (P>0.05). Results of multivariate analysis showed that fibroid location and ultrasound contrast intensity were independent influencing factors for HIFU treatment rate (P

Objective To report medium-term oncological outcomes in men receiving primary focal treatment with high-intensity focused ultrasonography ( HIFU) for prostate cancer (PCa). Patients and methods Consecutive patients with PCa treated with primary focal HIFU at two centres by six treating clinicians were assessed. Patients were submitted to either focal ablation or hemi-ablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium-term oncological outcomes, defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated with focal HIFU over time. We also assessed the relationship between year of surgery and 5-year retreatment probability. Results A total of 1032 men treated between November 2005 and October 2017 were assessed. The median age was 65 years and median prostate-specific antigen level was 7 ng/mL. The majority of patients had a Gleason score of 3 + 4 or above (80.3%). The median (interquartile range) follow-up was 36 (14-64) months. The overall survival rates at 24, 60 and 96 months were 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3 + 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85%, 59% and 46% at 24, 60 and 96 months, respectively. Approximately 70% of patients who were retreated received a second focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period, we observed an increase in the proportion of patients undergoing focal HIFU with Gleason 3 + 4 disease and with T2 stage disease as defined by multiparametric magnetic resonance imaging. Finally, there was a reduction over time in the proportion of patients undergoing re-treatment within 5 years of first treatment. Conclusions Focal HIFU for PCa is a feasible therapeutic strategy, with acceptable survival and oncological results and a reduction in the 5-year retreatment rates over the last decade. Re-do focal treatment is a feasible technique whose functional and oncological outcomes have still to be evaluated.

Highlights • 2D nonlinear wave propagation with a bubble at the HIFU focus is simulated. • Constructive interference of a backscattered wave with incoming shockwaves appears. • Shock scattering effect is the mechanism for the formation of a cavitation cloud., Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble. The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. A numerical simulation of 2D nonlinear wave propagation with the presence of a bubble at the focus of a HIFU field was performed using the k-Wave MATLAB toolbox for time domain ultrasound simulations, which numerically solves the generalised Westervelt equation. The numerical results clearly demonstrate the appearance of the constructive interference of a backscattered shockwave by a bubble with incoming incident shockwaves. This interaction (i.e., the reflected and inverted peak positive phase from the bubble with the incoming incident rarefactional phase) can eventually induce a greater peak negative pressure field compared to that without the bubble at the HIFU focus. In addition, the backscattered peak negative pressure magnitude gradually increased from 17.4 MPa to 31.6 MPa when increasing the bubble size from 0.2 mm to 1.5 mm. The latter value is above the intrinsic cavitation threshold of –28 MPa in soft tissue. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.

The heating effect produced by a focused ultrasound transducer has been investigated by using visual techniques with a positioning system. Ultrasound power, distance, frequency and harmonics of heating effect was investigated. Three experiments were performed on TMM (Tissue Mimicking Material), sheep liver and sheep lung. HIFU (High Intensity Focused Ultrasound) transducer with a resonance frequency of 1.1 MHz and 3.3 MHz was used as source. Effect of ultrasound in liver and lung's pieces were displayed and dimension of cauterization has been measured. Previous temperature measurement results for TMM were compared with liver and lung measurement results so that it is possible to transfer the laboratory measurements to the clinical studies. All measurements were carried out in the system at TUBITAK UME (The Scientific and Technological Research Council of Turkey, the National Metrology Institute) Ultrasound laboratory. (C) 2015 The Authors. Published by Elsevier B.V.

The drug release triggered thermally by high intensity focused ultrasound (HIFU) has been considered a promising drug delivery strategy due to its localized energy and non-invasive characters. However, the mechanism underlying the HIFU-mediated drug delivery remains unclear due to its complexity at the cellular level. In this paper, micro-HIFU (MHIFU) generated by a microfluidic device is introduced which is able to control the drug release from temperature-sensitive liposomes (TSL) and evaluate the thermal and mechanical effects of ultrasound on the cellular drug uptake and apoptosis. By simply adjusting the input electrical signal to the device, the temperature of sample can be maintained at 37 °C, 42 °C and 50 °C with the deviation of ± 0.3 °C as desired. The flow cytometry results show that the drug delivery under MHIFU sonication leads to a significant increase in apoptosis compared to the drug release by incubation alone at elevated temperature of 42 °C. Furthermore, increased squamous and protruding structures on the surface membrane of cells were detected by atomic force microscopy (AFM) after MHIFU irradiation of TSL. We demonstrate that compared to the routine HIFU treatment, MHIFU enables monitoring of in situ interactions between the ultrasound and cell in real time. Furthermore, it can quantitatively analyze and characterize the alterations of the cell membrane as a function of the treatment time.

High Intensity Focused Ultrasound (HIFU) can be used for the localized heating of biological tissue through the conversion of sound waves into heat. Although originally developed for human medicine, HIFU may also be used to weaken the attachment of pin bones in fish fillets to enable easier removal of such bones. This was shown in the present study, where a series of experiments were performed on HIFU phantoms and fillets of cod and salmon. In thin objects such as fish fillets, the heat is mainly dissipated at the surfaces. However, bones inside the fillet absorb ultrasound energy more efficiently than the surrounding tissue, resulting in a “self-focusing” heating of the bones. Salmon skin was found to effectively block the ultrasound, resulting in a significantly lower heating effect in fillets with skin. Cod skin partly blocked the ultrasound, but only to a small degree, enabling HIFU treatment through the skin. The treatment of fillets to reduce the pin bone attachment yielded an average reduction in the required pulling force by 50% in cod fillets with skin, with little muscle denaturation, and 72% in skinned fillets, with significant muscle denaturation. Salmon fillets were treated from the muscle side of the fillet to circumvent the need for penetration through skin. The treatment resulted in a 30% reduction in the peak pulling force and 10% reduction in the total pulling work, with a slight denaturation of the fillet surface.

Background The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. Methods Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients’ data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. Results In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C. Conclusions The TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Background Past catheter-based and focused ultrasound renal denervation studies have indicated that procedure efficacy is related to the number of ablations performed or the amount of energy used for the ablation. This study extends those prior results and investigates energy level effects on the efficacy of MR guided focused ultrasound renal denervation performed in a porcine model. Methods Twenty-four normotensive pigs underwent unilateral denervation at three intensity levels. The applied intensity level was retrospectively de-rated to account for variability in animal size. Efficacy was assessed through evaluating the norepinephrine present in the kidney medulla and through histological analysis. The treatment was performed under MRI guidance including pre- and post-procedure T1-weighted and quantitative T1 and T2 imaging. During treatment, the temperature in the near field of the ultrasound beam was monitored in real time with MR temperature imaging. Energy delivery in the regions surrounding the renal artery was independently confirmed through an invasive fiberoptic temperature probe placed in the right renal artery. Results Animals that underwent denervation at a de-rated acoustic intensity of greater than 1.2 kW/cm2 had a significantly lower norepinephrine concentration in the kidney indicating successful denervation. Images obtained during the treatment indicated no tissue changes in the kidneys as a function of the procedure but there were significant T1 changes present in the right lumbar muscles, although only one animal had indication of muscle damage at the time of necropsy. Conclusions While MR guided focused ultrasound renal denervation was found to be safe and effective in this normotensive animal model, the results indicated the need to incorporate patient-specific details in the treatment planning of MRgFUS renal denervation procedure.

Background With an increasing number of imaging studies being done nowadays, the number of incidentally discovered thyroid nodules is expected to rise. Although many of these nodules are small and benign in nature, some do grow and may cause pressure and/or thyrotoxic symptoms. Surgical resection has traditionally been recommended for symptomatic nodules but is associated with risk of hypothyroidism, bleeding, infection, and nerve damage. High intensity focused ultrasound (HIFU) is one of the non-surgical thermal ablation techniques that may serve as an alternative in the treatment of benign thyroid nodules. The present review is to systematically evaluate the efficacy and safety of HIFU ablation. Methods We comprehensively searched all studies that evaluated the use of HIFU ablation as a treatment of benign thyroid nodules from Medline (PubMed) and Cochrane Library electronic databases using specific keywords. All titles identified by the search strategy were independently screened by two authors. Case reports, animal studies, editorials, expert opinions, reviews without original data and studies on pediatric population were excluded. Multiple reports of the same dataset were assessed and the most representative and updated report of a study was included. Results Five original studies were found. All treated thyroid nodules were confirmed to be benign cytologically and either appeared solid or predominantly (>70%) solid on ultrasonography. Only one type of commercially available US-guided device with an extracorporeal probe (3 MHz) was used in all the reported treatments. No major complications including recurrent laryngeal nerve injury, skin burn or haematoma were reported in all of the studies. The overall nodule volume reduction after single session of HIFU ablation ranged between 45 and 68%, depending on nodule size and length of follow-up. Conclusions Despite the few number of studies, our review appeared to suggest that HIFU is a safe and efficacious method of treating symptomatic benign thyroid nodules. However, larger-scale, prospective trials with longer follow-up period are indeed required to confirm this. In terms of the ablation itself, relative to other ablation techniques, there are still much room for improvements in shortening treatment duration and expanding the range of treatable nodules.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapy modality in which ultrasound beams are concentrated at a focal region, producing a rise of temperature and selective ablation within the focal volume and leaving surrounding tissues intact. HIFU has been proposed for the safe ablation of both malignant and benign tissues and as an agent for drug delivery. Magnetic resonance imaging (MRI) has been proposed as guidance and monitoring method for the therapy. The identification of regions of interest is a crucial procedure in HIFU therapy planning. This procedure is performed in the MR images. The purpose of the present research work is to implement a time-efficient and functional segmentation scheme, based on the watershed segmentation algorithm, for the MR images used for the HIFU therapy planning. The achievement of a segmentation process with functional results is feasible, but preliminary image processing steps are required in order to define the markers for the segmentation algorithm. Moreover, the segmentation scheme is applied in parallel to an MR image data set through the use of a thread pool, achieving a near real-time execution and making a contribution to solve the time-consuming problem of the HIFU therapy planning. © 2017 A. Vargas-Olivares et al.

International audience; Background: During lengthy magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU) thermal ablations in abdominal organs, the therapeutic work-flow is frequently hampered by various types of physiological motion occurring at different time-scales. If left un-addressed this can lead to an incomplete therapy and/or to tissue damage of organs-at-risk. While previous studies focus on correction schemes for displacements occurring at a particular time-scale within the work-flow of an MRg-HIFU therapy, in the current work we propose a motion correction strategy encompassing the entire work-flow.Methods: The proposed motion compensation framework consists of several linked components, each being adapted to motion occurring at a particular time-scale. While respiration was addressed through a fast correction scheme, long term organ drifts were compensated using a strategy operating on time-scales of several minutes. The framework relies on a periodic examination of the treated area via MR scans which are then registered to a reference scan acquired at the beginning of the therapy. The resulting displacements were used for both on-the-fly re-optimization of the interventional plan and to ensure the spatial fidelity between the different steps of the therapeutic work-flow. The approach was validated in three complementary studies: an experiment conducted on a phantom undergoing a known motion pattern, a study performed on the abdomen of 10 healthy volunteers and during 3 in-vivo MRg-HIFU ablations on porcine liver.Results: Results have shown that, during lengthy MRg-HIFU thermal therapies, the human liver and kidney can manifest displacements that exceed acceptable therapeutic margins. Also, it was demonstrated that the proposed framework is capable of providing motion estimates with sub-voxel precision and accuracy. Finally, the 3 successful animal studies demonstrate the compatibility of the proposed approach with the work-flow of an MRg-HIFU intervention under clinical conditions.Conclusions: In the current study we proposed an image-based motion compensation framework dedicated to MRg-HIFU thermal ablations in the abdomen, providing the possibility to re-optimize the therapy plan on-the-fly with the patient on the interventional table. Moreover, we have demonstrated that even under clinical conditions, the proposed approach is fully capable of continuously ensuring the spatial fidelity between the different phases of the therapeutic work-flow.

The concept of ideal tumor surgery is to remove the neoplastic tissue without damaging adjacent normal structures. High-intensity focused ultrasound (HIFU) was developed in the 1940s as a viable thermal tissue ablation approach. In clinical practice, HIFU has been applied to treat a variety of solid benign and malig- nant lesions, including pancreas, liver, prostate, and breast carcinomas, soft tissue sarcomas, and uterine fibroids. More recently, magnetic resonance guidance has been applied for treatment monitoring during focused ultrasound procedures (magnetic resonance-guided focused ultra- sound, MRgFUS). Intraoperative magnetic resonance imaging provides the best possible tumor extension and dynamic control of energy deposition using real-time magnetic resonance imaging thermometry. We introduce the fundamental principles and clinical indications of the MRgFUS technique; we also report different treatment options and personal outcomes.

We have developed a non-invasive ultrasound theragnostic system (NIUTS) that tracks and follows the movement of an affected area (kidney stone/tumor, in this study) while irradiating it with high-intensity focused ultrasound (HIFU). In this paper, we propose a method to simplify extracting, tracking and following, monitoring the affected area by using a bed-type non-invasive ultrasound theragnostic system.

Objectives: Breast fibroadenomata (FAD) are the most common breast lumps in women. High intensity focused ultrasound (HIFU) is a non-invasive ablative technique that can be used to treat FAD but is associated with prolonged treatment times. In the HIFU-F trial, we evaluated the change in volume over time with circumferential HIFU treatment of FAD and compared this to no treatment. Methods: Patients ≥18 years, diagnosed with symptomatic, palpable FAD, visible on ultrasound (US) were recruited. Twenty patients were treated using US-guided HIFU under local anaesthesia. Another 20 participants underwent an US 6 months after diagnosis. Outcome measures included: reduction in treatment time compared to whole lesion ablation; feasibility to achieve a 50% reduction in volume after 6 months; decrease in volume compared to a control group and reduction in symptoms. Results: Circumferential ablation reduced the mean treatment time by 37.5% (SD 20.1%) compared to whole lesion ablation. US demonstrated a significant mean reduction in FAD volume of 43.5% (SD 38.8%; p = 0.016, paired t-test) in the HIFU group compared to 4.6% (SD 46.0%; p = 0.530) in the control group after 6 months. This mean reduction in FAD volume between the two groups was significant in favour of the HIFU group (p = 0.002, grouped t-test). Pre-treatment pain completely resolved in 6 out of 8 patients 6 months post-treatment. Conclusion: Circumferential HIFU ablation of FAD is feasible, with a significant reduction in pain and volume compared to control participants. It provides a simple, non-invasive, outpatient-based alternative to surgical excision for FAD.

Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.

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.