Multidisciplinary management to optimize outcome of ultrasound-guided high-intensity focused ultrasound (HIFU) in patients with uterine fibroids.

Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.

Incisionless MR-guided focused ultrasound: technical considerations and current therapeutic approaches in psychiatric disorders.

INTRODUCTION: MR-guided focused ultrasound operating at higher intensities have been reported to effectively and precisely ablate deeper brain structures like the basal ganglia or the thalamic nuclei for the treatment of refractory movement disorders, neuropathic pain and most recently neuropsychiatric disorders, while low-intensity focused ultrasound represents an approach promoting mechanical blood-brain-barrier opening and neuromodulation. This narrative review summarizes the technical development and the therapeutic potential of incisionless MRgFUS in order to treat neuropsychiatric disorders. AREAS COVERED: A narrative review of clinical trials assessing the safety and efficacy of MRgFUS. A literature review was performed using the following search terms: MR-guided focused ultrasound, psychiatric disorders, noninvasive and invasive brain modulation/stimulation techniques. EXPERT OPINION: MRgFUS ablation is under clinical investigation (unblinded study design) for obsessive-compulsive disorders (OCDs) [capsulotomy; ALIC] and depression/anxiety disorders [capsulotomy] and has demonstrated an improvement in OCD and depression, although of preliminary character. Low-intensity ultrasound applications have been explored in Alzheimer´s disease (phase 1 study) and healthy subjects. Currently, limited evidence hinders comparison and selection between MRgFUS and noninvasive/invasive brain modulation therapies. However, comparative, sham-controlled trials are needed to reexamine the preliminary findings for the treatment of psychiatric disorders.

An MRI-Guided Ring High-Intensity Focused Ultrasound System for Noninvasive Breast Ablation.

High-intensity focused ultrasound (HIFU) has been used for noninvasive treatment of breast tumors, but the present magnetic resonance imaging (MRI)-guided HIFU (MRI-HIFU) systems encounter skin burn. In this study, a novel MRI-HIFU breast ablation system was developed to improve the above problem. The system consisted of the ring HIFU phased-array transducer, a commercial power amplifier, the mechanical positioner, and the graphical user interface control software. MRI thermometry was also established to monitor the temperature in the HIFU-treated tissue. Ablation of pork and the in vivo rabbit leg were carried out to validate the developed system. Results of fat-surrounding pork ablation showed that the ring HIFU system reached a safe margin of 3 mm without fat burn. Moreover, precision of the positioner moving the HIFU focal zone was within 6% error under MRI circumstances. The representative MRI temperature images show that the peak temperatures among the five ablations ranged between 66 °C and 91 °C, and their thermal doses were over 10000. The system could also ablate the biceps femoris of a rabbit without skin burn to form a lesion of 2.5 mm beneath the skin. With the HIFU dose of 315 W/10 s, the MRI temperature map revealed that the maximum temperature and the thermal dose were 60 °C and 3380, respectively. The MRI-guided ring HIFU system can ablate the target tissue near subcutaneous fat without fat burn. The system prototype is a promising tool for clinical implementation.

HIFU Power Monitoring Using Combined Instantaneous Current and Voltage Measurement.

During high-intensity focused ultrasound (HIFU) therapy, it is important that the electrical power delivered to the transducer is monitored to avoid underexposure or overexposure, ensure patient safety, and to protect the transducer itself. Due to ease of measurement, the transducer's potential difference may be as an indicator of power delivery. However, even when a transducer's complex impedance is well characterized at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path, or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as a magnetic resonance imaging (MRI)-compatible, miniature alternative to bidirectional power couplers, which is compatible with switched amplifiers. For CCV power measurement, current probe data were multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers, there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery, leading to safer HIFU treatments.

Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: High-frequency ultrasound (HFUS 18-20 MHz) performed on patients with chronic inflammatory demyelinating polyneuropathy (CIDP) shows a focal enlargement, particularly in the proximal segments of upper-arm motor nerves. Ultrahigh frequency ultrasound (UHFUS 30-70 MHz), having a higher spatial resolution, enables a better characterization of nerve structures. The aim of this study was to compare the two ultrasound probes in the evaluation of motor nerve characteristics in CIDP patients. METHODS: Eleven patients with definite or probable CIDP underwent an ultrasound evaluation of median and ulnar nerves, bilaterally. Nerve and fascicle cross-sectional area (CSA), vascularization, and echogenicity were assessed. RESULTS: Nerve and fascicle CSA were increased in the proximal segments, especially in the median nerve, in 9/11 patients and in 10/11 patients at the HFUS and UHFUS evaluations, respectively. A statistically significant difference between CSA values obtained with the two probes was found only for fascicle values. UHFUS allowed for a more precise estimation of fascicle size and number than the HFUS. We were able to identify nerve vascularization in 4/11 patients at UHFUS only. CONCLUSION: UHFUS gives more detailed information on the changes in the internal nerve structure in CIDP patients. In particular, it permits to better characterize fascicle size and morphology, and to have a precise estimation of their number. Its frequency range also allows to evaluate nerve vascularization. SIGNIFICANCE: Ultrasound evaluation could become an adjunctive diagnostic tool for CIDP. Further studies are needed to validate the examined parameters as biomarkers for the evaluation and follow-up of CIDP patients.

Current applications and limitations of surgical treatments for movement disorders.

Functional neurosurgery for the treatment of both psychiatric and neurological disorders has been performed regularly since the 1940s. However, misuse in the early days and the appearance of effective medical treatments, such as levodopa and neuroleptic drugs, greatly reduced surgical approaches over several decades. The development of a comprehensive model of basal ganglia pathophysiology in the 1990s facilitated the resurgence of functional neurosurgery, mainly for the treatment of levodopa-related motor complications in Parkinson's disease. This led first to the re-emergence of posteroventral pallidotomy and subsequently to deep brain stimulation. Thirty years on from this turning point, we find ourselves looking at a new scenario. Although deep brain stimulation is accepted worldwide and technical advances continue to improve this therapy, new questions and challenges such as long-term benefits and optimal targeting have emerged. In addition, new nonincisional tools used to perform ablative treatments, such as high-intensity focused ultrasound and gamma-knife, are challenging classical reluctance to therapeutic lesioning, and it remains to be determined how these approaches will fit into the array of movement disorder treatments. This review discusses the current clinical state of the art of functional neurosurgery in the treatment of Parkinson's disease, tremor, and dystonia. © 2017 International Parkinson and Movement Disorder Society.

Historical ESWT Paradigms Are Overcome: A Narrative Review.

Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a historical consensus meeting in 1995 are to be revised. First, modern musculoskeletal ESWT is divided into focused and radial technology and the physical differences are about 100-fold with respect to the applied energy. Most lesions to be treated are easy to reach and clinical focusing plays a major role today. Lesion size is no longer a matter of concern. With the exception of nonunion fractures full, regional, or even local anesthesia is not helpful in musculoskeletal indications. Juvenile patients can also effectively be treated without risk of epiphyseal damage. Further research is needed to answer the question about if and which acute injuries can be managed effectively. Treatment parameters like the number of sessions are still relying on empirical data and have to be further elucidated.

A rapid magnetic resonance acoustic radiation force imaging sequence for ultrasonic refocusing.

Magnetic resonance guided acoustic radiation force imaging (MR-ARFI) is being used to correct for aberrations induced by tissue heterogeneities when using high intensity focusing ultrasound (HIFU). A compromise between published MR-ARFI adaptive solutions is proposed to achieve efficient refocusing of the ultrasound beam in under 10 min. In addition, an ARFI sequence based on an EPI gradient echo sequence was used to simultaneously monitor displacement and temperature with a large SNR and low distortion. This study was conducted inside an Achieva 3T clinical MRI using a Philips Sonalleve MR-HIFU system to emit a 1 ms pulsed sonication with duty cycle of 2.3% at 300 Wac inside a polymer phantom. Virtual elements defined by a Hadamard array with sonication patterns composed of 6 phase steps were used to characterize 64 groups of 4 elements to find the optimal phase of the 256 elements of the transducer. The 384 sonication patterns were acquired in 580 s to identify the set of phases that maximize the displacement at the focal point. Three aberrators (neonatal skull, 8 year old skull and a checkered pattern) were added to each sonication pattern to evaluate the performance of this refocusing algorithm (n = 4). These aberrators reduced the relative intensities to 95.3%, 69.6% and 25.5% for the neonatal skull, 8 year old skull, and checkered pattern virtual aberrators respectively. Using a 10 min refocusing algorithm, relative intensities of 101.6%, 91.3% and 93.3% were obtained. Better relative intensities of 103.9%, 94.3% and 101% were achieved using a 25 min refocusing algorithm. An average temperature increase of 4.2 °C per refocusing test was induced for the 10 min refocusing algorithm, resulting in a negligible thermal dose of 2 EM. A rapid refocusing of the beam can be achieved while keeping thermal effects to a minimum.

A new design method for extracorporeal high-intensity focused ultrasound annular array.

Considering the damage to normal tissues during the high-intensity focused ultrasound ablation of the tumor is important. The purpose of this work was to design the annular array under the considerations of preventing the skin burn and damage to normal tissues behind the tumor target. Based on the Rayleigh-Summerfield pressure integral, the numerical acoustic intensity field of a spherical bowl annular array with a diameter of 12 cm and a radius of curvature of 12 cm was obtained by using the MATLAB software. An absorbed intensity ratio of the normal tissue to target was proposed to define the allowable grating lobe for determining the focusing range. The analytic results showed that for the treatment of uterine fibroids, the focusing range increased as the number of the element increased from 9 to 22 and the 14-ring array at the operating frequency of 0.8, 0.9 or 1.0 MHz had a focusing range larger than 5.5 cm when the range was only 4 cm at 1.2 MHz. For the treatment of medullary carcinoma and scirrhous carcinoma in breast, the focusing range of the 0.9-MHz, 14-ring annular array was 8-12 and 8-14 cm, respectively.

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function.

OBJECT: Tumors at the skull base are challenging for both resection and radiosurgery given the presence of critical adjacent structures, such as cranial nerves, blood vessels, and brainstem. Magnetic resonance imaging-guided thermal ablation via laser or other methods has been evaluated as a minimally invasive alternative to these techniques in the brain. Focused ultrasound (FUS) offers a noninvasive method of thermal ablation; however, skull heating limits currently available technology to ablation at regions distant from the skull bone. Here, the authors evaluated a method that circumvents this problem by combining the FUS exposures with injected microbubble-based ultrasound contrast agent. These microbubbles concentrate the ultrasound-induced effects on the vasculature, enabling an ablation method that does not cause significant heating of the brain or skull. METHODS: In 29 rats, a 525-kHz FUS transducer was used to ablate tissue structures at the skull base that were centered on or adjacent to the optic tract or chiasm. Low-intensity, low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes after intravenous injection of an ultrasound contrast agent (Definity, Lantheus Medical Imaging Inc.). Using histological analysis and visual evoked potential (VEP) measurements, the authors determined whether structural or functional damage was induced in the optic tract or chiasm. RESULTS: Overall, while the sonications produced a well-defined lesion in the gray matter targets, the adjacent tract and chiasm had comparatively little or no damage. No significant changes (p > 0.05) were found in the magnitude or latency of the VEP recordings, either immediately after sonication or at later times up to 4 weeks after sonication, and no delayed effects were evident in the histological features of the optic nerve and retina. CONCLUSIONS: This technique, which selectively targets the intravascular microbubbles, appears to be a promising method of noninvasively producing sharply demarcated lesions in deep brain structures while preserving function in adjacent nerves. Because of low vascularity--and thus a low microbubble concentration--some large white matter tracts appear to have some natural resistance to this type of ablation compared with gray matter. While future work is needed to develop methods of monitoring the procedure and establishing its safety at deep brain targets, the technique does appear to be a potential solution that allows FUS ablation of deep brain targets while sparing adjacent nerve structures.

Quantitative assessment of acoustic intensity in the focused ultrasound field using hydrophone and infrared imaging.

With the popularity of ultrasound therapy in clinics, characterization of the acoustic field is important not only to the tolerability and efficiency of ablation, but also for treatment planning. A quantitative method was introduced to assess the intensity distribution of a focused ultrasound beam using a hydrophone and an infrared camera with no prior knowledge of the acoustic and thermal parameters of the absorber or the configuration of the array elements. This method was evaluated in both theoretical simulations and experimental measurements. A three-layer model was developed to calculate the acoustic field in the absorber, the absorbed acoustic energy during the sonication and the consequent temperature elevation. Experiments were carried out to measure the acoustic pressure with the hydrophone and the temperature elevation with the infrared camera. The percentage differences between the derived results and the simulation are <4.1% for on-axis intensity and <21.1% for -6-dB beam width at heating times up to 360 ms in the focal region of three phased-array ultrasound transducers using two different absorbers. The proposed method is an easy, quick and reliable approach to calibrating focused ultrasound transducers with satisfactory accuracy.

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation.

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from B-mode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimeter-sized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.

Development and characterization of a tissue-mimicking material for high-intensity focused ultrasound.

A tissue-mimicking material (TMM) for the acoustic and thermal characterization of high-intensity focused ultrasound (HIFU) devices has been developed. The material is a high-temperature hydrogel matrix (gellan gum) combined with different sizes of aluminum oxide particles and other chemicals. The ultrasonic properties (attenuation coefficient, speed of sound, acoustical impedance, and the thermal conductivity and diffusivity) were characterized as a function of temperature from 20 to 70°C. The backscatter coefficient and nonlinearity parameter B/A were measured at room temperature. Importantly, the attenuation coefficient has essentially linear frequency dependence, as is the case for most mammalian tissues at 37°C. The mean value is 0.64f(0.95) dB·cm(-1) at 20°C, based on measurements from 2 to 8 MHz. Most of the other relevant physical parameters are also close to the reported values, although backscatter signals are low compared with typical human soft tissues. Repeatable and consistent temperature elevations of 40°C were produced under 20-s HIFU exposures in the TMM. This TMM is appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU devices.

Effects of gas pockets on high-intensity focused ultrasound field.

The paper describes experimental and numerical studies of the effects of gas pockets on a high-intensity focused ultrasound (HIFU) field. Air bubbles ranging from 0.8 to 2.4 mm in radius were produced in transparent polyacrylamide tissue-mimicking gels. A single-element 3.5-MHz HIFU transducer was used to sonicate the gel phantoms. The changes in the HIFU beam pattern for air bubbles at different positions were visualized by the Schlieren method. Quantitative measurements of pressure at the HIFU focus by a calibrated needle hydrophone showed considerable reduction in the focal pressure with the presence of an air pocket. The presence of a single 1.2-mm-radius air bubble, at a 5 mm axial pre-focal position, reduced the focal intensity by 50% and increased the lateral focal dimension by 50%. For air bubbles at pre-focal position close to the focus, lesion formation was observed not at the theoretical focus, but in front of the air bubble and the air bubble became a barrier for the post-focal ultrasound propagation. The effects of reflection were simulated numerically and were compared with the experiments. The results can be used as guidelines for evaluation of potential safety concerns produced by trapped gas-pockets in various HIFU therapies.

Characterization of a fiber-optic displacement sensor for measurements in high-intensity focused ultrasound fields.

A fiber-optic sensor is presented that is capable of measuring the particle displacement in high-intensity focused ultrasound (HIFU) fields. For this probe, a secondary calibration was performed, and the resulting complex frequency response is discussed. As a first practical application, the setup was used to measure the pressure in the field of a weakly focusing ultrasound transducer. The result is compared with that of a membrane hydrophone measurement. The feasibility of measurements in HIFU fields is demonstrated by means of measurements of the spatial distribution of the peak particle velocity within the focus of a HIFU transducer and of the dependence of the peak values on the acoustical power level.