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.

A fast full-wave solver for calculating ultrasound propagation in the body.

Therapeutic ultrasound is a promising non-invasive method for inducing various beneficial biological effects in the human body. In cancer treatment applications, high-power ultrasound is focused at a target tissue volume to ablate the malignant tumour. The success of the procedure depends on the ability to accurately focus ultrasound and destroy the target tissue volume through coagulative necrosis whilst preserving the surrounding healthy tissue. Patient-specific treatment planning strategies are therefore being developed to increase the efficacy of such therapies, while reducing any damage to healthy tissue. These strategies require to use high-performance computing methods to solve ultrasound wave propagation in the body quickly and accurately. For realistic clinical scenarios, all numerical methods which employ volumetric meshes require several hours or days to solve the full-wave propagation on a computer cluster. The boundary element method (BEM) is an efficient approach for modelling the wave field because only the boundaries of the hard and soft tissue regions require discretisation. This paper presents a multiple-domain BEM formulation with a novel preconditioner for solving the Helmholtz transmission problem (HTP). This new formulation is efficient at high-frequencies and where high-contrast materials are present. Numerical experiments are performed to solve the HTP in multiple domains comprising: (i) human ribs, an idealised abdominal fat layer and liver tissue, (ii) a human kidney with a perinephric fat layer, exposed to the acoustic field generated by a high-intensity focused ultrasound (HIFU) array transducer. The time required to solve the equations associated with these problems on a single workstation is of the order of minutes. These results demonstrate the great potential of this new BEM formulation for accurately and quickly solving ultrasound wave propagation problems in large anatomical domains which is essential for developing treatment planning strategies.

3D synthetic aperture imaging with a therapeutic spherical random phased array for transcostal applications.

Experimental validation of a synthetic aperture imaging technique using a therapeutic random phased array is described, demonstrating the dual nature of imaging and therapy of such an array. The transducer is capable of generating both continuous wave high intensity beams for ablating the tumor and low intensity ultrasound pulses to image the target area. Pulse-echo data is collected from the elements of the phased array to obtain B-mode images of the targets. Since therapeutic arrays are optimized for therapy only with concave apertures having low f-number and large directive elements often coarsely sampled, imaging can not be performed using conventional beamforming. We show that synthetic aperture imaging is capable of processing the acquired RF data to obtain images of the field of interest. Simulations were performed to compare different synthetic aperture imaging techniques to identify the best algorithm in terms of spatial resolution. Experimental validation was performed using a 1 MHz, 256-elements, spherical random phased array with 130 mm radius of curvature. The array was integrated with a research ultrasound scanner via custom connectors to acquire raw RF data for variety of targets. Imaging was implemented using synthetic aperture beamforming to produce images of a rib phantom and ex vivo ribs. The array was shown to resolve spherical targets within ±15 mm of either side of the axis in the focal plane and obtain 3D images of the rib phantom up to ±40 mm of either side of the central axis and at a depth of 3-9 cm from the array surface. The lateral and axial full width half maximum was 1.15 mm and 2.75 mm, respectively. This study was undertaken to emphasize that both therapy and image guidance with a therapeutic random phased array is possible and such a system has the potential to address some major limitations in the existing high intensity focused ultrasound (HIFU) systems. The 3D images obtained with a therapeutic array can be used to identify and locate strong scattering objects aiding to image guidance and treatment planning of the HIFU procedure.

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

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

High-Power Phased-Array Transducer Module for the Construction of a System for the Treatment of Deep Vein Thrombosis.

Blood clot can be disintegrated by high-intensity focused ultrasound alone through inertial cavitation. There are limitations in using single-element ultrasound transducers for this purpose such as lack of steerability and control of the focus in terms of shape and location. Phased-array transducers being able to rapidly scan over the clots can alleviate this problem. A full 3-D control of the ultrasound beam can be achieved by 2-D electronically steerable arrays. However, the required high-pressure amplitude has not been possible with such arrays. In this work, a 2-D 64-element fully populated phased-array transducer module was designed and fabricated for the high-pressure amplitude required for deep vein thrombosis (DVT). Lateral coupling was considered for the transducer design to decrease the electrical impedance and eliminate the need for electrical matching circuit. PZT-4 with a thickness of 0.35 mm, an element surface area of [Formula: see text] mm, and a length of 6 mm showed a mean electrical impedance of 60.4 ± 11.5 measured for each transducer element facilitating effective electric power transfer from the driving electronics. No breakdown was observed when the voltage was increased gradually to 180 ± 3 Vpp. Operation at 180 Vpp was found to be safe over 10,000 repetitions without reduction in the power, resulting in the average pressure amplitude of 1.01 ± 0.09 MPa at 2 mm from the element surface. These pressure amplitude values indicate that an array of eight modules (80 [Formula: see text] mm) is required to reach to the pressure amplitude needed for DVT. Such arrays are practical with the current technology.

Minimally invasive therapeutic ultrasound: Ultrasound-guided ultrasound ablation in neuro-oncology.

INTRODUCTION: To improve patient outcomes (eg, reducing blood loss and infection), practitioners have gravitated toward noninvasive and minimally invasive surgeries (MIS), which demand specialized toolkits. Focused ultrasound, for example, facilitates thermal ablation from a distance, thereby reducing injury to surrounding tissue. Focused ultrasound can often be performed noninvasively; however, it is more difficult to carry out in neuro-oncological tumors, as ultrasound is dramatically attenuated while propagating through the skull. This shortcoming has prompted exploration of MIS options for intracranial placement of focused ultrasound probes, such as within the BrainPath™ (NICO Corporation, Indianapolis, IN). Herein, we present the design, development, and in vitro testing of an image-guided, focused ultrasound prototype designed for use in MIS procedures. This probe can ablate neuro-oncological lesions despite its small size. MATERIALS & METHODS: Preliminary prototypes were iteratively designed, built, and tested. The final prototype consisted of three 8-mm-diameter therapeutic elements guided by an imaging probe. Probe functionality was validated on a series of tissue-mimicking phantoms. RESULTS: Lesions were created in tissue-mimicking phantoms with average dimensions of 2.5 × 1.2 × 6.5 mm and 3.4 × 3.25 × 9.36 mm after 10- and 30-second sonification, respectively. 30 s sonification with 118 W power at 50% duty cycle generated a peak temperature of 68 °C. Each ablation was visualized in real time by the built-in imaging probe. CONCLUSION: We developed and validated an ultrasound-guided focused ultrasound probe for use in MIS procedures. The dimensional constraints of the prototype were designed to reflect those of BrainPath trocars, which are MIS tools used to create atraumatic access to deep-seated brain pathologies.

Ultrafast three-dimensional microbubble imaging in vivo predicts tissue damage volume distributions during nonthermal brain ablation.

Transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) thermal ablation is under clinical investigation for non-invasive neurosurgery, though its use is restricted to central brain targets due primarily to skull heating effects. The combination of FUS and contrast agent microbubbles greatly reduces the ultrasound exposure levels needed to ablate brain tissue and may help facilitate the use of transcranial FUS ablation throughout the brain. However, sources of variability exist during microbubble-mediated FUS procedures that necessitate the continued development of systems and methods for online treatment monitoring and control, to ensure that excessive and/or off-target bioeffects are not induced from the exposures. Methods: Megahertz-rate three-dimensional (3D) microbubble imaging in vivo was performed during nonthermal ablation in rabbit brain using a clinical-scale prototype transmit/receive hemispherical phased array system. Results:In-vivo volumetric acoustic imaging over microsecond timescales uncovered spatiotemporal microbubble dynamics hidden by conventional whole-burst temporal averaging. Sonication-aggregate ultrafast 3D source field intensity data were predictive of microbubble-mediated tissue damage volume distributions measured post-treatment using MRI and confirmed via histopathology. Temporal under-sampling of acoustic emissions, which is common practice in the field, was found to impede performance and highlighted the importance of capturing adequate data for treatment monitoring and control purposes. Conclusion: The predictive capability of ultrafast 3D microbubble imaging, reported here for the first time, will enable future microbubble-mediated FUS treatments with unparalleled precision and accuracy, and will accelerate the clinical translation of nonthermal tissue ablation procedures both in the brain and throughout the body.

Precision Targeted Ablation of Fine Neurovascular Structures In Vivo Using Dual-mode Ultrasound Arrays.

Carotid bodies (CBs) are chemoreceptors that monitor and register changes in the blood, including the levels of oxygen, carbon dioxide, and pH, and regulate breathing. Enhanced activity of CBs was shown to correlate with a significant elevation in the blood pressure of patients with hypertension. CB removal or denervation were previously shown to reduce hypertension. Here we demonstrate the feasibility of a dual-mode ultrasound array (DMUA) system to safely ablate the CB in vivo in a spontaneously hypertensive rat (SHR) model of hypertension. DMUA imaging was used for guiding and monitoring focused ultrasound (FUS) energy delivered to the target region. In particular, 3D imaging was used to identify the carotid bifurcation for targeting the CBs. Intermittent, high frame rate imaging during image-guided FUS (IgFUS) delivery was used for monitoring the lesion formation. DMUA imaging provided feedback for closed-loop control (CLC) of the lesion formation process to avoid overexposure. The procedure was tolerated well in over 100 SHR and normotensive rats that received unilateral and bilateral treatments. The measured mean arterial pressure (MAP) exhibited measurable deviation from baseline 2-4 weeks post IgFUS treatment. The results suggest that the direct unilateral FUS treatment of the CB might be sufficient to reduce the blood pressure in hypertensive rats and justify further investigation in large animals and eventually in human patients.

Real-time and multimodality image-guided intelligent HIFU therapy for uterine fibroid.

Rationale: High-intensity focused ultrasound (HIFU) therapy represents a noninvasive surgical approach to treat uterine fibroids. The operation of HIFU therapy relies on the information provided by medical images. In current HIFU therapy, all operations such as positioning of the lesion in magnetic resonance (MR) and ultrasound (US) images are manually performed by specifically trained doctors. Manual processing is an important limitation of the efficiency of HIFU therapy. In this paper, we aim to provide an automatic and accurate image guidance system, intelligent diagnosis, and treatment strategy for HIFU therapy by combining multimodality information. Methods: In intelligent HIFU therapy, medical information and treatment strategy are automatically processed and generated by a real-time image guidance system. The system comprises a novel multistage deep convolutional neural network for preoperative diagnosis and a nonrigid US lesion tracking procedure for HIFU intraoperative image-assisted treatment. In the process of intelligent therapy, the treatment area is determined from the autogenerated lesion area. Based on the autodetected treatment area, the HIFU foci are distributed automatically according to the treatment strategy. Moreover, an image-based unexpected movement warning and other physiological monitoring are used during the intelligent treatment procedure for safety assurance. Results: In the experiment, we integrated the intelligent treatment system on a commercial HIFU treatment device, and eight clinical experiments were performed. In the clinical validation, eight randomly selected clinical cases were used to verify the feasibility of the system. The results of the quantitative experiment indicated that our intelligent system met the HIFU clinical tracking accuracy and speed requirements. Moreover, the results of simulated repeated experiments confirmed that the autodistributed HIFU focus reached the level of intermediate clinical doctors. Operations performed by junior- or middle-level operators with the assistance of the proposed system can reach the level of operation performed by senior doctors. Various experiments prove that our proposed intelligent HIFU therapy process is feasible for treating common uterine fibroid cases. Conclusion: We propose an intelligent HIFU therapy for uterine fibroid which integrates multiple medical information processing procedures. The experiment results demonstrated that the proposed procedures and methods can achieve monitored and automatic HIFU diagnosis and treatment. This research provides a possibility for intelligent and automatic noninvasive therapy for uterine fibroid.

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.

Deployable tessellated transducer array for ultrasound focusing and bio-heat generation in a multilayer environment.

High intensity focused ultrasound (HIFU) has great potential to thermally ablate diseased tissues with minimal invasion. Yet, HIFU practice has limited cancer treatment potential since the absorption, diffusion, and reflection of ultrasound prevent HIFU from penetrating the body to deep and concealed diseased tissue. To explore a vision of deployable HIFU transducers, this research introduces an origami-inspired concept wherein a deployable tessellated acoustic array is employed to reduce the distance between the HIFU transducer and diseased tissues. A flat-foldable HIFU transducer array is considered, such that the compact shape is used to pass through the human body and then deployed into the operational form for treatment. Here a theoretical framework is developed to study the focusing and thermal heating capabilities of the tessellated array in a multilayer environment. It is observed that the wavefield and thermal elevation realized by the foldable array are functionally similar to those of an ideal arc-shaped transducer. Folding patterns that permit adequate curvature and high quality factor, and that balance slenderness and conformability are found to be beneficial for an ultrasound focusing practice. The efficacy of the analytical predictions are verified through direct numerical simulations. All together, the results encourage attention to foldable array concepts as potential means to advance in-vivo HIFU-based procedures.

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.

Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney.

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5-30 pulses of 1-10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9-3.8 kW, sonication foci spaced 1-1.5 mm apart in a rectangular grid with 5-15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.

Delay multiply and sum beamforming method applied to enhance linear-array passive acoustic mapping of ultrasound cavitation.

PURPOSE: Passive acoustic mapping (PAM) has been proposed as a means of monitoring ultrasound therapy, particularly nonthermal cavitation-mediated applications. In PAM, the most common beamforming algorithm is a delay, sum, and integrate (DSAI) approach. However, using DSAI leads to low-quality images for the case where a narrow-aperture receiving array such as a standard B-mode linear array is used. This study aims to propose an enhanced linear-array PAM algorithm based on delay, multiply, sum, and integrate (DMSAI). METHODS: In the proposed algorithm, before summation, the delayed signals are combinatorially coupled and multiplied, which means that the beamformed output of the proposed algorithm is the spatial coherence of received acoustic emissions. We tested the performance of the proposed DMSAI using both simulated and experimental data and compared it with DSAI. The reconstructed cavitation images were evaluated quantitatively by using source location errors between the two algorithms, full width at half maximum (FWHM), size of point spread function (A50 area), signal-to-noise ratio (SNR), and computational time. RESULTS: The results of simulations and experiments for single cavitation source show that, by introducing DMSAI, the FWHM and the A50 area are reduced and the SNR is improved compared with those obtained by DSAI. The simulation results for two symmetric or nonsymmetric cavitation sources and multiple cavitation sources show that DMSAI can significantly reduce the A50 area and improve the SNR, therefore improving the detectability of multiple cavitation sources. CONCLUSIONS: The results indicate that the proposed DMSAI algorithm outperforms the conventionally used DSAI algorithm. This work may have the potential of providing an appropriate method for ultrasound therapy monitoring.

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.

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.

A rapid beam simulation framework for transcranial focused ultrasound.

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

Experimental study in vivo ablation of swine pancreas using high-intensity focused ultrasound.

OBJECTIVE: The objective of this study is to evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) for ablation of swine pancreas and to detect the pathological variations in pancreas damage. MATERIALS AND METHODS: (a) Eight swine were involved and randomly divided into two groups (Group A and B). HIFU was applied on swine in both groups for in vivo ablation of pancreas. The animals were anesthetized, and the artificial acoustic window was built. Then, the irradiation of FEP-BY02 type HIFU on pancreas was applied. (b) Swine in Group A were euthanized immediately after treating with HIFU to examine variations in pancreas. The biochemical evidence of pancreatitis was evaluated by blood samples collected from swine in Group B before and after HIFU. Then, the pancreas of swine in Group B was euthanized on day 5 after treatment to examine the pancreas. All specimens were visually inspected for both ultrasonic focal damage region (UFDR) and pathological routine by a skilled pathologist. RESULTS: (a) The vital signs of all animals were stable during HIFU treatment and recovered well after treatment. (b) UFDR were observed in all HIFU irradiation region of the specimens, without significant size difference between the two groups. The coagulation nucleus pyknosis, cytochylema vacuolation, and nucleus membrane disruption were observed after HIFU in both groups. Membranous structure dissolution and inflammatory cell infiltration were also found after HIFU in swine of Group B. (c) There was no significant difference in the levels of blood amylase in swine of Group B before and after HIFU treatment. CONCLUSIONS: It was feasible and safe to use HIFU for ablation of the pancreas in swine.

Real-Time Photoacoustic Thermometry Combined With Clinical Ultrasound Imaging and High-Intensity Focused Ultrasound.

High-intensity focused ultrasound (HIFU) treatment is a promising non-invasive method for killing or destroying the diseased tissues by locally delivering thermal and mechanical energy without damaging surrounding normal tissues. In HIFU, measuring the temperature at the site of delivery is important for improving therapeutic efficacy, controlling safety, and appropriately planning a treatment. Several researchers have proposed photoacoustic thermometry for monitoring HIFU treatment, but they had many limitations, including the inability to image while the HIFU is on, inability to provide two-dimensional monitoring, and the inability to be used clinically. In this paper, we propose a novel integrated real-time photoacoustic thermometry system for HIFU treatment monitoring. The system provides ultrasound B-mode imaging, photoacoustic structural imaging, and photoacoustic thermometry during HIFU treatment in real-time for both in vitro and in vivo environments, without any interference from the strong therapeutic HIFU waves. We have successfully tested the real-time photoacoustic thermometry by investigating the relationship between the photoacoustic amplitude and the measured temperature with in vitro phantoms and in vivo tumor-bearing mice. The results show the feasibility of a real-time photoacoustic thermometry system for safe and effective monitoring of HIFU treatment.

Enhanced Numerical Method for the Design of 3-D-Printed Holographic Acoustic Lenses for Aberration Correction of Single-Element Transcranial Focused Ultrasound.

The correction of transcranial focused ultrasound aberrations is a relevant issue for enhancing various non-invasive medical treatments. The emission through multi-element phased arrays has been the most widely accepted method to improve focusing in recent years; however, the number and size of transducers represent a bottleneck that limits the focusing accuracy of the technique. To overcome this limitation, a new disruptive technology, based on 3-D-printed acoustic lenses, has recently been proposed. As the submillimeter precision of the latest generation of 3-D printers has been proven to overcome the spatial limitations of phased arrays, a new challenge is to improve the accuracy of the numerical simulations required to design this type of ultrasound lens. In the study described here, we evaluated two improvements in the numerical model applied in previous works for the design of 3-D-printed lenses: (i) allowing the propagation of shear waves in the skull by means of its simulation as an isotropic solid and (ii) introduction of absorption into the set of equations that describes the dynamics of the wave in both fluid and solid media. The results obtained in the numerical simulations are evidence that the inclusion of both s-waves and absorption significantly improves focusing.