Ultrasound imaging guided precision histotripsy: Effects of pulse settings on ablation properties in rat brain.

A high-frequency 6 MHz miniature handheld histotripsy device with an endoscopic form factor and co-registered high-resolution ultrasound imaging was developed. This device could allow precision histotripsy ablation during minimally invasive brain tumor surgeries with real-time image guidance. This study characterized the outcome of acute histotripsy in the normal in vivo rat brain using the device with a range of histotripsy pulse settings, including number of cycles, pulse repetition frequency, and pressure, as well as other experimental factors. The stability and shape of the bubble cloud were measured during ablations, as well as the post-histotripsy ablation shape in ultrasound B-mode and histology. The results were compared between histological images and the ultrasound imaging data to determine how well ultrasound data reflected observable damage in histology. The results indicated that while pulse settings can have some influence on ablation shape, sample-to-sample variation had a larger influence on ablation shape. This suggests that real-time ablation monitoring is essential for accurate knowledge of outcomes. Ultrasound imaging provided an accurate real-time indication of ablation shape both during ablation and post-ablation.

How technology is driving the landscape of epilepsy surgery.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.

Development of temperature controller-integrated portable HIFU driver for thermal coagulation.

BACKGROUND: Temperature monitoring during high-intensity focused ultrasound (HIFU) therapy on tissue is essential to regulate the degree of thermal coagulation and to achieve the desired treatment outcomes eventually. The aim of the current study was to design and investigate the feasibility of a proportional-integral-derivative (PID) temperature controller-integrated portable HIFU driver for thermal coagulation. METHODS: A portable HIFU driver was designed and operated at a maximum output voltage of 50 V with pulse-width modulation signals at 2 MHz. The temperature of ex vivo bovine liver tissue was monitored using a K-type thermocouple during the 2-MHz HIFU exposure. RESULTS: The tissue temperature was maintained at 60 °C using a PID controller-integrated HIFU driver that modulated the output voltage during the 300-s HIFU exposure. The ex vivo testing demonstrated that the tissue temperature at the focal point approached the chosen temperature, i.e., 60 °C, within 70 s. The temperature was maintained with a deviation of less than 4 °C until the HIFU driver voltage was turned off at 300 s. CONCLUSIONS: The designed PID controller-integrated HIFU driver can be used as a small portable tool to regulate the tissue temperature in real time and achieve thermal coagulation via HIFU sonication.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

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

BACKGROUND: 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 200-2000 kHz as required for deep axial penetration of the body. HIFU utilizing frequencies in excess of 15 MHz has so far not been explored, but presents an opportunity to extend the HIFU modality to target specific dermal lesions and small animal research. MATERIALS AND METHODS: 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. RESULTS: The system produces highly reproducible ultrasound lesions with predictable and configurable depths of 1-2 mm, thus corresponding to the depth of the human dermis. The lesion geometry was elongated triangular and sized 0.1-0.5 mm, 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. CONCLUSION: 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.

A numerical study on thermal ablation of brain tumor with intraoperative focused ultrasound.

Focused ultrasound surgery (FUS) is a non-invasive thermal therapeutic method which has been emerged in the field of brain tumors treatment. During intraoperative brain surgery, application of FUS can significantly increase the accuracy of thermal ablation of tumor while reducing undesirable damage to healthy brain tissue. The main objective of this study is acquiring acoustic transducer specifications to achieve optimum thermal treatment in the tumoral tissue. 2D and 3D models are constructed from patient-specific brain MRI images which consist of a malignant vascular tumor. Acoustic pressure and temperature are obtained by using homogenous Helmholtz and bio-heat transfer equations according to insignificant nonlinear effect. Besides that, thermal lesion induced by FUS is obtained by the thermal dose function. Results show the significance of blood vessels' cooling effect on the temperature profile. Moreover, correlation between temperature profile and transducer's operating parameter including power, frequency and duty cycle is obtained. Artificial neural network analysis is conducted to estimate required transducer parameters for optimum temperature rise.

Technical aspects of osteoid osteoma ablation in children using MR-guided high intensity focussed ultrasound.

BACKGROUND: Osteoid osteoma (OO) is a painful bone tumour occurring in children and young adults. Magnetic resonance imaging-guided high intensity focussed ultrasound (MR-HIFU) allows non-invasive treatment without ionising radiation exposure, in contrast to the current standard of care treatment with radiofrequency ablation (RFA). This report describes technical aspects of MR-HIFU ablation in the first 8 paediatric OO patients treated in a safety and feasibility clinical trial (total enrolment of up to 12 patients). MATERIALS AND METHODS: OO lesions and adjacent periosteum were treated with MR-HIFU ablation in 5-20 sonications (sonication duration = 16-48 s, frequency = 1.2 MHz, acoustic power = 20-160 W). Detailed treatment workflow, patient positioning and coupling strategies, as well as temperature and tissue perfusion changes were summarised and correlated. RESULTS: MR-HIFU ablation was feasible in all eight cases. Ultrasound standoff pads were shaped to conform to extremity contours providing acoustic coupling and aided patient positioning. The energy delivered was 10 ± 7 kJ per treatment, raising maximum temperature to 83 ± 3 °C. Post ablation contrast-enhanced MRI showed ablated volumes ranging 0.46-19.4 cm3 extending further into bone (7 ± 4 mm) than into soft tissue (4 ± 6 mm, p = 0.01, Mann-Whitney). Treatment time ranged 30-86 min for sonication and 160 ± 40 min for anaesthesia. No serious treatment-related adverse events were observed. Complete pain relief with no medication occurred in 7/8 patients within 28 days following treatment. CONCLUSIONS: MR-HIFU ablation of painful OO appears technically feasible in children and it may become a non-invasive and radiation-free alternative for painful OO. Therapy success, efficiency, and applicability may be improved through specialised equipment designed more specifically for extremity bone ablation.

Complications from microfocused transcutaneous ultrasound: Case series and review of the literature.

BACKGROUND AND OBJECTIVE: Microfocused ultrasound (MFUS) technology has been utilized since 2009 for improvement in mild to moderate skin and soft tissue laxity of the face and neck. Few complications have been previously reported, the majority of which include mild and transient erythema, edema, ecchymosis, and nerve paralysis. Rare yet serious potential complications of MFUS for noninvasive skin tightening of the face and neck are, however, possible. METHODS & MATERIALS: Retrospective multicenter case series of five patients from the authors' practice who developed serious adverse events directly related to MFUS with a commercially available device (Ultherapy; Merz North America, Inc., Raleigh, NC). RESULTS: Five patients developed blistering, erosion/ulceration, cutaneous, or subcutaneous tissue edema with resulting atrophy, and/or cutaneous necrosis following single sessions of MFUS. CONCLUSION: Despite their rarity, serious adverse events secondary to MFUS are nevertheless possible and may be underreported. Early management of complications includes local wound care, patient reassurance, and topical corticosteroids and/or pulsed-dye laser to mitigate inflammatory sequelae. Other cosmetic and surgical therapies should be utilized when conservative measures have failed. Lasers Surg. Med. 50:13-19, 2018. © 2017 Wiley Periodicals, Inc.

Assessment of Gold Nanoparticle-Mediated-Enhanced Hyperthermia Using MR-Guided High-Intensity Focused Ultrasound Ablation Procedure.

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.

Numerical evaluation of the effect of electronically steering a phased array transducer: axially post-focal shifting.

PURPOSE: HIFU has been emerging as an effective and safe modality for the treatment of solid tumours and cancers. The focus shifting range of phased array HIFU transducer is an important safety concern because of the presence of grating lobe in the pre-focal region. However, previous studies were only based on linear acoustic wave model. MATERIALS AND METHODS: The nonlinear wave propagation from a 256-element phased array through multiple layered media was simulated using the angular spectrum approach (ASA) in marching fractional steps with the consideration of diffraction, attenuation and non-linearity effects by a second-order operator splitting scheme. The distribution of acoustic intensities, temperature elevations, lesion sizes and grating lobe levels were calculated at various axially post-focal shifting distances and driving frequencies. RESULTS: Axially shifting HIFU focus leads to significant increase of the acoustic intensity at the grating lobe, but decrease at the main lobe. The influences on the acoustic field, thermal field and lesion sizes are determined by the shifting distance and driving frequency, and variations can be fit monotonically and linearly. Prediction accuracies by simple regression models are satisfactory. Irreversible tissue coagulation could be generated by the grating lobe at certain conditions. CONCLUSIONS: The established nonlinear wave propagation algorithm allows the accurate description of HIFU field and consequently the evaluation of grating lobe and steerability of focus. The influence of focus shifting may be predicted simply. The treatment planning of phased array HIFU ablation could be optimised by setting the appropriate exposure and focus scanning schemes.

High-intensity focused ultrasound treatment for skin: ex vivo evaluation.

BACKGROUND/PURPOSE: High-intensity focused ultrasound (HIFU) has been used for skin tightening. However, there is a rising concern of irreversible adverse effects. Our aim was to evaluate the depth of thermal injury zone after HIFU energy passes through different condition. MATERIALS AND METHODS: To analyze the consistency of the HIFU device, phantom tests were performed. Simulations were performed on ex vivo porcine tissues to estimate the area of the thermal coagulation point (TCP) according to the applied energy and skin condition. The experiment was designed in three orientations: normal direction (from epidermis to fascia), reverse direction (from fascia to epidermis), and normal direction without epidermis. RESULTS: The TCP was larger and wider depending on the applied fluence and handpieces (HPs). When we measured TCP in different directions, the measured area in the normal direction was more superficially located than that in the reverse direction. The depth of the TCP in the porcine skin without epidermis was detected at 130% deeper than in skin with an intact epidermis. CONCLUSION: The affected area by HIFU is dependent on the skin condition and the characteristics of the HP and applied fluence. Considerations of these factors may be the key to minimize the unwanted adverse effects.

Improved methods for evaluating pre-clinical and histological effects of subcutaneous fat reduction using high-intensity focused ultrasound in a porcine model.

BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. AIMS: The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model. METHODS: The abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™ , Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. RESULTS: HIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR-delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed. CONCLUSION: We successfully used a HIFU device for body contouring and fat reduction in a pre-clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.

Pilot Study of the Mirabilis System Prototype for Rapid Noninvasive Uterine Myoma Treatment Using an Ultrasound-Guided Volumetric Shell Ablation Technique.

STUDY OBJECTIVE: The primary objective of this pilot study was to evaluate the safety and acute tissue ablation efficacy of a transabdominal high-intensity focused ultrasound (HIFU) prototype device that uses ultrasound imaging guidance for rapid noninvasive ablation of uterine myomas. The secondary objective was to assess preliminary myoma-related symptom improvement and myoma volume reduction at 3 to 6 months post-treatment in subsets of patients. DESIGN: Multicenter prospective single-arm pilot study (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital and private community hospital. PATIENTS: Women with a diagnosis of symptomatic uterine myomas planning to undergo hysterectomy. INTERVENTIONS: Seventy-three women underwent transabdominal ultrasound-guided HIFU treatment using a volumetric ablation technique referred to as "shell ablation," in which the HIFU energy is deposited in patterns that partially encapsulate the peripheral region of the targeted myoma(s). Patients were divided into 2 sequential cohorts, the development cohort (the first 37 patients treated) and the validation cohort (the final 36 patients treated). Development cohort treatments were performed for dose-ranging purposes to identify the optimum HIFU treatment parameters, whereas the validation cohort treatments were performed to validate these final settings. Sixty-five patients (89.0%) received only prophylactic oral, sublingual, or intramuscular analgesia before treatment, sometimes with oral anxiolytics. The remaining 8 patients (11.0%) were anesthetized before treatment. Sixty-seven patients (91.8%) then had scheduled hysterectomies between 0 and 179 days after treatment completion. Adverse events were monitored until study exit, which ranged from 10 to 191 days post-treatment. MEASUREMENTS AND MAIN RESULTS: The primary efficacy endpoint measured in all 73 patients was the nonperfused volume (NPV) of tissue produced, which was assessed between 0 and 7 days post-treatment either by tissue sectioning after hysterectomy or by gadolinium-enhanced magnetic resonance imaging. Secondary efficacy endpoints were also measured in subsets of patients who were prospectively scheduled for delayed hysterectomies: Changes in menstrual blood loss (MBL), symptom severity (SS), and quality of life (QOL) scores were assessed using validated techniques at 3 months post-treatment in 10 patients and changes in treated myoma volume were assessed using magnetic resonance imaging at 3 to 6 months post-treatment in 14 patients. In all 73 patients, there were no reports of any serious adverse device effects, including no damage to any extrauterine collateral tissues or the abdominal skin. In the development cohort, a mean NPV of 17.9 ± 24.9 cm3 (range, 0-123.0) was produced in a mean total treatment time of 4.9 ± 2.4 minutes (range, 1.1-11.3). These metrics improved in the validation cohort, where a mean NPV of 44.9 ± 58.5 cm3 (range, 0-284.7) was produced in a mean total treatment time of 3.6 ± 2.1 minutes (range, 1.5-9.5). In the subsets of patients with data available, there was a significant improvement in QOL score (median, 16.5 point increase; p = .011), an improving trend in SS score (median, 13.5 point decrease; p = .254), and a significant improvement in treated myoma volume (mean, 24.0% decrease; p = .013). In 8 patients who had above-average MBL scores at baseline and regular menstrual cycle lengths during follow-up, there was also a significant improvement in MBL score (median, 40.8% decrease; p = .035). CONCLUSION: Ultrasound-guided HIFU ablation with the prototype device demonstrated an excellent safety profile and produced clinically relevant NPVs in a mean total treatment time of under 4 minutes using the final validated treatment settings. Short-term clinical efficacy metrics assessed in subsets of patients were encouraging, and larger studies should be conducted to confirm these results (ClinicalTrials.gov, NCT01946178).

Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model.

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

Medical Devices; Gastroenterology-Urology Devices; Classification of the High Intensity Ultrasound System for Prostate Tissue Ablation. Final order.

The Food and Drug Administration (FDA or we) is classifying the high intensity ultrasound system for prostate tissue ablation into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the high intensity ultrasound system for prostate tissue ablation's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Design of a low power hybrid HIFU applicator for haemostasis based on acoustic propagation modelling.

PURPOSE: The aim of this study was to design an applicator for haemostasis usage needing lower acoustic intensities (<880 W/cm(2)) than in previous devices intended for it, which is based on ultrasound propagation FEM modelling using a 2-MHz HIFU transducer. MATERIALS AND METHODS: Acoustic field characterisation and numerical simulations in water were performed with and without the proposed applicator. Parameters such as form factor, ellipsoidal shape ratio, and Euclidean distance were used (among others) to compare simulated data with transducer measurements without applicator. A low density polyethylene cone was manufactured from geometries validated from acoustic field modelling. The hollow cone was filled with 10% polyacrylamide gel as a coupling medium with liver phantom or chicken liver. Focal temperature was measured with a thermocouple embedded in the phantom for 1-20 W driving powers for 120 s. Standing wave ratios (SWR) were used as coupling indexes. Ex vivo experimentation in chicken liver was made at 10-20 W. RESULTS: Simulated acoustic patterns showed good concordance with measurements. Experimental focal distance was 20.72 ± 0.24 mm, while the simulated was 19.79 mm (≈4% error). SWR at low power were: 2.01 with transducer emitting in air, 1.53 at applicator tip, and 1.35 after phantom placement. Average SWR at high power was 1.31. Similarity of percentages for data comparison in focal plane was over 60%. Maximum temperature measured at focus was 88.7 °C with 20 W after 85 s. CONCLUSIONS: Temperatures reached at focus suggest that this applicator has good efficiency, which notably reduces the power typically needed for haemostasis effect.

Evaluation of a novel device, high-intensity focused ultrasound with a contact cooling for subcutaneous fat reduction.

BACKGROUND: Non-invasive devices for fat reduction involving high-intensity focused ultrasound (HIFU) are attracting attention. HIFU can deliver energy to the desired depth and can ablate subcutaneous adipose tissue (SAT), but purpura and pain may still limit its use. OBJECTIVES: The aim of this study was to investigate the effects of a novel HIFU device for fat destruction with a contact cooling system compared to HIFU without contact cooling. METHODS: A group of three pigs were administered a series of four HIFU treatments with or without contact cooling over a period of 12 weeks. Energy fluence parameters ranged from 60 to 300 J/cm2 . Immediately after the treatment and at 1, 4, and 12 weeks, the tissue was studied by hematoxylin and eosin (H&E), Masson-trichrome, toluidine blue, CD68 staining, and transmission electron microscopy. Three human volunteers also received treatment with this HIFU device with cooling and were evaluated subjectively and objectively by computed tomography (CT). RESULTS: HIFU treatment with a contact cooling decreased the skin surface temperature and prevented epidermal damage. Ecchymosis was observed on the non-cooled area immediately after HIFU treatment, but not on the cooled area. Histological analyses on both areas (cooled and non-cooled) revealed disrupted adipocytes in the treatment area immediately, at 1 and 4 weeks following treatment. Lipophagic histiocytic fat necrosis was evident at 4 weeks. Finally, at 12 weeks all inflammation subsided, and the lobules were markedly atrophied with reduced SAT thickness. The human volunteers experienced reduction of a few centimeter-range reduction in waist circumference after 4 weeks and pain was tolerable without bruising. CONCLUSIONS: HIFU treatment with a cooling system efficiently destroyed adipocytes. This novel HIFU device with an added contact cooling system may provide an effective, safe and less painful treatment as a non-invasive device for fat reduction. Lasers Surg. Med. 48:878-886, 2016. © 2016 Wiley Periodicals, Inc.

The safety and efficacy of thermal lipolysis of adipose tissue via ultrasound for circumference reduction: An open label, single-arm exploratory study.

BACKGROUND AND OBJECTIVE: To better understand adipocyte sensitivity under hyperthermic conditions, the ULTIMA system (also known as MUST) was designed to induce the thermal destruction of fat cells using ultrasound, radiofrequency, and vacuuming. This clinical study assessed the safety and efficacy of ULTIMA in non-invasive reductions of abdominal circumference. STUDY DESIGN: This open-label, single-arm exploratory study monitored the response of 21 patients to a single fat reduction treatment session with the ULTIMA system. Male and female patients between the ages of 18 and 65 who presented with a subcutaneous adipose fat thickness >2.5 cm as measured with a caliper and 2 cm as measured by ultrasound were eligible to participate in the study. Patients with a history of surgery in the target region and who had previous fat/circumference reduction treatments within the previous 6 months were excluded. Efficacy measures evaluated at the 1-, 2-, and 3-month post-treatment visits included the following: photographs of before and after treatment as evaluated by two blinded reviewers, changes from the baseline abdominal circumference and fat layer thickness, and subjective physician and patient assessments. Immediate skin responses were recorded for up to 30 minutes post-treatment, and adverse events were recorded throughout the study. RESULTS: An average of 10 zones per patient were subjected to ULTIMA treatment and 87.5% of the pre-treatment photographs were correctly rated by two independent blinded reviewers. A statistically and clinically significant reduction in the abdominal circumference was observed at 3 months post-treatment. The changes in circumference (represented as the mean ± SE) of the baseline of the anterior superior iliac spine (ASIS), umbilicus, and maximal circumference during this period were -3.2 ± 0.7 cm, -3.9 ± 0.7 cm, and -3.3 ± 0.8 cm, respectively. Physician-based assessments classified all patients (100%) as "improved" within 3 months of treatment, and self-assessment questionnaires completed by the patients demonstrated that 92% of them classified their conditions as either improved or much improved within this same time period. Any immediate skin reactions observed fell within the expected norms and were short-lived and self-resolving. CONCLUSIONS: A single ULTIMA treatment session effectively and safely resulted in visual appearance improvement and in a significant reduction in the patients' abdominal circumference, which persisted for 3 months. Additional investigations will be required to further optimize the treatment regimen and assess its long-term sustainability. Lasers Surg. Med. 48:734-741, 2016. © 2016 Wiley Periodicals, Inc.

Ovarian Reserve After Ultrasound-Guided High-Intensity Focused Ultrasound for Uterine Fibroids: Preliminary Experience.

OBJECTIVE: To determine the effect on ovarian reserve of ultrasound-guided high-intensity focused ultrasound (HIFU) in the treatment of uterine fibroids. METHODS: We performed a mid-study analysis of markers of ovarian reserve using data from a prospective cohort study evaluating the safety of ultrasound-guided HIFU for uterine fibroids. Blood samples obtained from 12 women with uterine fibroids less than one week before treatment were used for measurement of serum anti-Mullerian hormone (AMH), and this testing was repeated in the first, third, sixth, and 12th month after ultrasound-guided HIFU treatment. RESULTS: Fourteen fibroids from 12 patients were treated using ultrasound-guided HIFU. The median baseline fibroid volume was 101.2 cm(3) (range 18.5 to 349.2 cm(3)). The median treatment time was 140.5 minutes (46 to 192 minutes), and median sonication time was 1449 seconds (range 541 to 2445 seconds). The median energy delivered was 575 521.5 joules (range 216 400 to 898 273 joules). The median AMH levels (ng/mL) before treatment and at one, three, six, and 12 months after treatment were 0.3 (range 0.01 to 1.94), 0.47 (0.01 to 1.43), 0.205 (0.01 to 1.81), 0.26 (0 to 2.37), and 0.06 (0.02 to 1.04), respectively. There was no significant difference between the AMH levels before and at any time after treatment. No patient became amenorrheic or reported symptoms suggestive of menopause after treatment. CONCLUSION: Our preliminary experience suggests that ovarian reserve does not seem to be affected by ultrasound-guided HIFU in the treatment of uterine fibroids.