High Intensity Focused Ultrasound Thermal Ablation Research Articles

Design by stochastic simulations of the thermal ablation treatment of tumors with high intensity focused ultrasound

High Intensity Focused Ultrasound (HIFU) is a noninvasive technique that can be applied for the thermal ablation of tumors with minimum side effects. Numerical simulations have been used for the selection of individualized thermal ablation treatments, but mathematical models depend on several parameters that are commonly known with large uncertainties. This computational work presents the design of the thermal ablation of tumors heated with HIFU by using the Markov Chain Monte Carlo method, implemented via the Metropolis-Hastings algorithm with sequential sampling of two blocks of parameters. Two-dimensional regions with tumors of different sizes were considered. The heating period and the position of the HIFU transducer were considered as the design variables, with priors modeled by uniform distributions. Other model parameters that appeared in the mathematical formulation were assumed Gaussian. The likelihood function, which represented the desired outcome of the thermal ablation treatment and its associated uncertainties, was modeled by a beta distribution for the probability of cell death due to heating. The obtained results revealed that the version of the Metropolis-Hastings algorithm used in this work could deal with uncertainties in the model parameters and allowed the robust design of the HIFU thermal ablation of the region of interest.

Enabling Chemo-Immunotherapy with HIFU in Canine Cancer Patients.

High intensity focused ultrasound (HIFU) is a promising non-invasive technique for treating solid tumors using thermal and histotripsy-based mechanical ablation. However, its clinical significance in different tumor types is not fully understood. To assess its therapeutic efficacy and immunomodulatory properties, we compared HIFU thermal ablation and histotripsy ablation in dogs with spontaneous tumors. We also evaluated the ability of non-ablative HIFU-based mild hyperthermia (40-45 ºC) to improve Doxorubicin delivery and immunomodulation. Our results showed that HIFU thermal ablation induced tumor remission in the majority of treated patients over 60days, while histotripsy achieved partial response to stable disease persistence. The adverse effects of thermal ablation were minor to moderate, while histotripsy exposures were relatively well-tolerated. Furthermore, we observed a correlation between HIFU-therapeutic response and serum anti-tumor cytokine profiles and the presence of functionally active cytotoxic immune cells in patients. Similarly, Doxorubicin-treated patients showed improved drug delivery, efficacy, and anti-tumor immune responses with HIFU hyperthermia. In conclusion, our study demonstrates that depending on the tumor type and treatment parameters, HIFU treatments can enable tumor growth control, immune activation, and chemotherapy in veterinary patient. These findings have significant clinical implications and highlight the potential of HIFU as a promising cancer treatment approach.

Development of a Numerical Model of High-Intensity Focused Ultrasound Treatment in Mobile and Elastic Organs: Application to a Beating Heart

High-intensity focused ultrasound (HIFU) is a promising method used to treat cardiac arrhythmias, as it can induce lesions at a distance throughout myocardium thickness. Numerical modeling is commonly used for ultrasound probe development and optimization of HIFU treatment strategies. This study was aimed at describing a numerical method to simulate HIFU thermal ablation in elastic and mobile heart models. The ultrasound pressure field is computed on a 3-D orthonormal grid using the Rayleigh integral method, and the attenuation is calculated step by step between cells. The temperature distribution is obtained by resolution of the bioheat transfer equation on a 3-D non-orthogonally structured curvilinear grid using the finite-volume method. The simulation method is applied on two regions of the heart (atrioventricular node and ventricular apex) to compare the thermal effects of HIFU ablation depending on deformation, motion type and amplitude. The atrioventricular node requires longer sonication than the ventricular apex to reach the same lesion volume. Motion considerably influences treatment duration, lesion shape and distribution in cardiac HIFU treatment. These results emphasize the importance of considering local motion and deformation in numerical studies to define efficient and accurate treatment strategies.

Enhancing Thermal Effect of Focused Ultrasound Therapy Using Gold Nanoparticles.

High intensity focused ultrasound (HIFU) has gained increasing attention as a noninvasive therapeutic method for wide range of biomedical applications from drug delivery to cancer treatment. However, high level of ultrasonic power required for efficient HIFU treatment can cause adverse effects such as damage to surrounding healthy tissues and skin burns. One of the strategies to improve the therapeutic mechanism of HIFU is to use ultrasound absorption agents during the treatment. The objectives of current study are to investigate the feasibility of adopting gold nanoparticles (AuNPs) as ultrasound absorption agents to enhance the HIFU thermal ablation when the NPs were injected locally to the focal region; and to examine the dose effects of AuNPs on both heating and cooling mechanisms of HIFU. To this end, we conducted an experimental study on tissue-mimicking phantoms where AuNPs were injected to the focal region under the guidance of ultrasound imaging. A set of thermal parameters including temperature, specific absorption rate of acoustic energy, and cooling rate were measured to monitor the mechanism of AuNPs-mediated HIFU. The results suggest that both heating and cooling rates of HIFU procedure could be greatly improved by injecting AuNPs, which demonstrates the feasibility of using AuNPs to reduce the level of ultrasonic power from extracorporeal source for HIFU treatment.

Ultrasonic Nakagami Imaging of High-intensity Focused Ultrasound-induced Thermal Lesions in Porcine Livers: Ex Vivo Study.

High-intensity focused ultrasound (HIFU) has demonstrated the capacity to be used for local thermal ablation in clinical surgery; however, relying solely on conventional ultrasound B-mode imaging to monitor HIFU thermal ablation and determine ablation levels remains a challenge. Here, we experimentally demonstrate the ability to use Nakagami imaging to monitor HIFU-induced thermal lesions in porcine livers ex vivo. Ultrasonic Nakagami imaging has been proven to be able to characterize tissues with different scatterer concentrations and distributions. The pathological sections from HIFU thermally ablated porcine liver tissues reveal that normal and denatured tissues significantly differ in scatterer concentration and distribution. Therefore, we believe that Nakagami imaging can be used to monitor thermal ablation by tracing Nakagami parameter changes in liver tissues. The ex vivo porcine liver experiments were performed using a homemade HIFU device synchronized with a commercial diagnostic ultrasound scanner to obtain the ultrasound envelope data before and after thermal ablation. These data were used to evaluate the performance of thermal lesion characterization using Nakagami imaging and were compared with those derived from conventional B-mode imaging. Experimental results showed that Nakagami imaging can be used to identify thermal lesions, which are difficult to visualize using conventional B-mode imaging because there is no apparent bubble formation. In cases with apparent bubble formation, Nakagami imaging could provide a more accurate estimation of lesion size and position. In addition, the Nakagami imaging algorithm is characterized by low computational complexity, which means it can be easily integrated as postprocessing for existing array imaging systems.

Real-Time Spatiotemporal Control of High-Intensity Focused Ultrasound Thermal Ablation Using Echo Decorrelation Imaging in ex Vivo Bovine Liver

The ability to control high-intensity focused ultrasound (HIFU) thermal ablation using echo decorrelation imaging feedback was evaluated in ex vivo bovine liver. Sonications were automatically ceased when the minimum cumulative echo decorrelation within the region of interest exceeded an ablation control threshold, determined from preliminary experiments as −2.7 (log-scaled decorrelation per millisecond), corresponding to 90% specificity for local ablation prediction. Controlled HIFU thermal ablation experiments were compared with uncontrolled experiments employing two, five or nine sonication cycles. Means and standard errors of the lesion width, area and depth, as well as receiver operating characteristic curves testing ablation prediction performance, were computed for each group. Controlled trials exhibited significantly smaller average lesion area, width and treatment time than five-cycle or nine-cycle uncontrolled trials and also had significantly greater prediction capability than two-cycle uncontrolled trials. These results suggest echo decorrelation imaging is an effective approach to real-time HIFU ablation control.

Real-time feedback control of high-intensity focused ultrasound thermal ablation using echo decorrelation imaging

The feasibility of controlling high-intensity focused ultrasound (HIFU) thermal ablation in real time using echo decorrelation imaging feedback was investigated in ex vivo bovine liver. Sonication cycles (5.0 MHz, 0.7 s per HIFU pulse, 20-24% duty, 879-1426 W/cm2 spatial-peak, and temporal peak intensity) performed by a linear image-ablate array were repeated until the minimum cumulative echo decorrelation within the focal region of interest exceeded a predefined threshold. Based on preliminary experiments (N = 13), a threshold of −2.7 for the log10-scaled echo decorrelation per millisecond was defined, corresponding to 90% specificity of local ablation prediction. Controlled HIFU thermal ablation experiments (N = 10) were compared with uncontrolled experiments employing 2, 5, or 9 sonication cycles. Controlled trials showed significantly smaller average lesion area (4.78 mm2), lesion width (1.29 mm), and treatment time (5.8 s) than 5-cycle (7.02 mm2, 1.89 mm, 14.5 s) or 9-cycle (9.31 mm2, 2.4 mm, 26.1 s) uncontrolled trials. Prediction of local ablation using echo decorrelation was assessed using receiver operator characteristic (ROC) curve analysis, in which controlled trials showed significantly greater prediction capability (area under the ROC curve AUC = 0.956) compared to 2-cycle uncontrolled trials (AUC = 0.722). These results suggest that ablation control using echo decorrelation may improve the precision, reliability, and duration of ultrasound-guided HIFU treatments.

Comparison of the synergistic effect of lipid nanobubbles and SonoVue microbubbles for high intensity focused ultrasound thermal ablation of tumors

Microbubbles (MBs) are considered as an important enhancer for high intensity focused ultrasound (HIFU) treatment of benign or malignant tumors. Recently, different sizes of gas-filled bubbles have been investigated to improve the therapeutic efficiency of HIFU thermal ablation and reduce side effects associated with ultrasound power and irradiation time. However, nanobubbles (NBs) as an ultrasound contrast agent for synergistic therapy of HIFU thermal ablation remain controversial due to their small nano-size in diameter. In this study, phospholipid-shell and gas-core NBs with a narrow size range of 500–600 nm were developed. The synergistic effect of NBs for HIFU thermal ablation was carefully studied both in excised bovine livers and in breast tumor models of rabbits, and made a critical comparison with that of commercial SonoVue microbubbles (SonoVue MBs). In addition, the pathological changes of the targeted area in tumor tissue after HIFU ablation were further investigated. Phosphate buffer saline (PBS) was used as the control. Under the same HIFU parameters, the quantitative echo intensity of B-mode ultrasound image and the volume of coagulative necrosis in lipid NBs groups were significantly higher and larger than that in PBS groups, but could not be demonstrated a difference to that in SonoVue MBs groups both ex vivo and in vivo. These results showed that the synergistic effect of lipid NBs for HIFU thermal ablation were similar with that of SonoVue MBs, and further indicate that lipid NBs could potentially become an enhancer for HIFU thermal ablation of tumors.

Cardiac shear-wave elastography using a transesophageal transducer: application to the mapping of thermal lesions in ultrasound transesophageal cardiac ablation

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesion’s extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions.First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle () and mapped (). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n = 3), then atrial (left, ) and ventricular (left , right ) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE.During the cardiac cycle stiffness varied from 0.5 ± 0.1 kPa to 6.0 ± 0.3 kPa in the atrium and from 1.3 ± 0.3 kPa to 13.5 ± 9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3 ± 5.5 kPa (versus 4.4 ± 1.6 kPa before ablation) in the chicken breast, to 30.3 ± 10.3 kPa (versus 12.2 ± 4.3 kPa) in the atria and to 73.8 ± 13.9 kPa (versus 21.2 ± 3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm2 in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1: −0.8 mm; third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm2 and a median of 0.2 mm (Q1: −2.7 mm; Q3: 2.7 mm) for a MSE of 11.1 mm2 from gross pathology.We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias.

Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer.

Harmonic motion imaging (HMI) is a radiationforce- based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess the resulting oscillatory displacement denoting the underlying tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radio-frequency signals using a 1-D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated at a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring.

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the −3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p < 0.002 in the 2D HMI system. We demonstrated the feasibility of using this HMI-based technique to localize the HIFU focal spot without inducing thermal changes during the planning phase. The focal spot localization method has also been applied on ex vivo human breast tissue ablation and can be fully integrated into any HMI system for planning purposes.

Direct nanodroplet and microbubble comparison for high intensity focused ultrasound ablation enhancement and safety

High intensity focused ultrasound (HIFU) surgery often requires hours of ablation in order to treat an entire tumor. Both perfluorocarbon gaseous microbubbles and vaporized liquid droplets are known enhancers of HIFU thermal ablation. Microbubbles, however, often lead to surface or skin lesions. Furthermore, they have a relatively short half-life in vivo (minutes) rendering them insufficiently stable for an entire HIFU surgery, which can last several hours. Many droplet formulations require very high pressures to activate. Our aim was to design an agent that could shorten ablation procedures without sacrificing safety. We designed and investigated a perfluorocarbon nanodroplet composed of a 1:1 ratio of dodecafluoropentane and decafluorobutane. These are tuned to change phase and activate at only 2 MPa peak negative pressure with common HIFU pulse lengths, enabling focused and targeted activation. Additionally, they are stable at body temperature.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P < 0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P < 0.05) after PSNE injection. For example, the mean per cent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.

DYNAMIC CHANGES IN THE ACOUSTO-MECHANICAL AND STATISTICAL PARAMETERS OF TISSUE DURING HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) TREATMENT

High intensity focused ultrasound (HIFU) induces focalized tissue coagulation by increasing the tissue temperature in a tight focal region and has been successfully used as a new technique of tumor treatment or to stop bleeding in clinical applications. The main challenges of this technique are: adjusting the location of HIFU thermal ablation exactly at the region of interest, and controlling the level of thermal ablation. Several imaging methods have been proposed to monitor HIFU-induced thermal lesions such as X-ray, MRI and ultrasound imaging. Currently, ultrasound imaging techniques that are clinically used for monitoring HIFU treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation, and elastography-based methods. This study was carried on ex vivo animal tissue samples. Backscattered radio frequency (RF) signals were acquired in real-time including before, during and after HIFU treatment. In this study, first we estimate the dynamic changes in the acoustical, mechanical and statistical parameters of the tissue resulted from HIFU exposures with three different acoustic powers. Then, we use these parameters to detect the induced HIFU thermal lesions and monitor the treatment process. By estimating the standard deviation of the studied parameters along acquired RF data frames, we show that there are significant changes in the tissue properties during the HIFU treatment.

Image-based computational model for focused ultrasound ablation of liver tumor

High-intensity focused ultrasound (HIFU) is a rapidly developing medical technology that allows non-invasive thermal ablation of tumors. Thermal treatment of liver tumor, which is one of the most common malignancies worldwide, is problematic because large blood vessels act as a heat sink. Convective cooling protects the cancer cells from thermal destruction and decreases the necrosed volume. A major objective of the method development is to achieve a virtually complete necrosis of tumors close to major blood vessels and to avoid blood vessel damage and, hence, the needed treatment planning. The present study is aimed at predicting liver tumor temperature during HIFU thermal ablation in a patient-specific liver geometry. The model comprises the nonlinear Westervelt equation and bioheat equations in the liver and blood vessels. The nonlinear hemodynamic equations are also taken into account with the convected cooling and acoustic streaming effects being taken into account. We found from this three-dimensional three-field coupling study that in large blood vessels, both convective cooling and acoustic streaming may change the temperature considerably near the blood vessel. More precisely, acoustic streaming velocity magnitude can be several times larger than the blood vessel velocity. The results presented in the current work can be further used to construct a surgical planning platform.

Temperature–density hysteresis in X-ray CT during HIFU thermal ablation: Heating and cooling phantom study

Purpose: This paper investigated the effects of thermal ablation treatment on imaged X-ray computed tomography (CT) Hounsfield units (HU), for the purpose of monitoring tissue denaturation and coagulation.Materials and methods: Eight phantoms of water, oil, and chicken serum albumin as well as 15 ex vivo tissue samples were heated by applying high intensity focused ultrasound (HIFU) for 10 to 29 min to obtain denaturation temperatures, (i.e. >50 °C). X-ray CT scanning was performed simultaneously during heating and post-ablation cooling stages, and the HU at the focal zone were registered. The temperature profile versus time was also monitored under similar conditions using a thermocouple probe. The results were plotted and correlated as curves of HU versus temperature.Results: In all specimens studied, HU values depicted an exponential curve as a function of temperature during the heating stage. However, linear behaviour was observed during the cool-down stage for both chicken serum albumin and ex vivo bovine liver. Thus, a hysteresis phenomenon occurred only when the thermal conditions induced irreversible changes in the sample with quantification demonstrating high correlation with the maximal temperature reached during treatment (R2 > 0.9) for the chicken serum albumin.Conclusions: Our results demonstrate a HU–temperature hysteresis phenomenon for HIFU ablation, which is detectible by X-ray CT. This hysteresis is related to the amount of heat induced into the tissue and could potentially indicate irreversible tissue damage. Accordingly, this measurable phenomenon can be utilised as a quantitative method for non-invasive monitoring of thermal ablation.

Enhanced Heat Transfer and Thermal Dose Using Magnetic Nanoparticles During HIFU Thermal Ablation—An In-Vitro Study

Avoiding collateral damage to healthy tissues during the high intensity focused ultrasound (HIFU) ablation of malignant tumors is one of the major challenges for effective thermal therapy. Such collateral damage can originate out of the need for using higher acoustic powers to treat deep seated or highly vascularized tumors. The objective of this study is to assess the utility of using magnetic nanoparticles (mNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral thermal damage and undesired destruction due to cavitation. Tissue phantoms with 0% (control), 1% and 3% mNPs concentrations by volume were fabricated. Each tissue phantom was embedded with four thermocouples (TCs) and sonicated using transducer acoustic powers of 5.15 W, 9.17 W, and 14.26 W. The temperature profiles during the heating and cooling periods were recorded for each embedded TC. The measured transient temperature profiles were used for thermal-dose calculations. The increase in the concentration of mNPs in the tissue phantoms, from 0% to 3%, resulted in the rise in the peak temperatures for all the TCs for each acoustic power. The thermal dose also increased with the rise in the concentration of mNPs in the tissue phantoms. For the highest applied acoustic power (14.26 W), the peak temperature at TC 1 (T1) in tissue phantoms with 1% and 3% mNPs concentrations increased (with respect to tissue phantom with 0% (control) mNPs concentration) by 1.59× and 2.09×, respectively. For an acoustic power of 14.26 W, the time required to achieve cellular necrosis as defined by a 240 equivalent min thermal dose was approximately 75 s in the absence of mNPs, 14 s for the 1% concentration, and 8 s for the 3% concentration. Magnetic nanoparticles have the potential to significantly reduce the time for HIFU thermal-ablation procedures. They can also decrease the likelihood of collateral damage by the propagating beam in HIFU procedures by reducing the intensity required to achieve cellular necrosis.

SU-E-U-06: MR-Guided Focused Ultrasound After Uterine Artery Embolization: What Happens to the Embosphere Microspheres?

Introduction: In order to select appropriate candidates for treatment of uterine fibroids using MR guided focused ultrasound (MRgFUS), a careful review of the patients' history and imaging is required. Not infrequently, patients with uterine fibroids seeking MRgFUS have previously undergone uterine artery embolization (UAE). The most common embolic agent used during UAE is Embosphere microspheres (Merit Medical Systems, INC, South Jordan, UT). Following UAE, the microspheres remain in the capillary beds of the fibroid vessels indefinitely. However, little is known regarding the nature of Embosphere microspheres in the setting of elevated temperatures (65–85degrees C) generated by high intensity focused ultrasound (HIFU). Embosphere microspheres are made of an acrylic co-polymer (trisacryl), which is cross-linked with gelatin. The aim of the present study was to evaluate for changes in Embosphere microspheres that underwent HIFU. Purpose: To evaluate for changes in shape and nature of Embosphere microspheres following MRgFUS.Materials and Methods: 10cc of 500–700micron Embosphere microspheres were injected into chicken breast. HIFU thermal ablation was performed, reaching high enough temperature to coagulate the chicken breast surrounding the microspheres. Additionally a vial containing microspheres was placed in a bath of heating water and temperature monitoring was performed until a maximum temperature of 100 degrees C. Gross and microscopic evaluation of the microspheres following HIFU and waterbath heating was performed. Results: The microspheres maintained their normal structure without evidence of denaturing or melting when targeted directly with HIFU (Figure 1). Additionally, the microspheres in boiling water did not alter their shape and structural integrity (Figure 2). Conclusion: HIFU of Embosphere microspheres does not change the structural integrity of the particles. As such, in the setting of prior UAE with Embosphere microspheres, MRgFUS may be safe without inducing particle denaturing or melting.

The Effect of the Scanning Pathway in High-Intensity Focused Ultrasound Therapy on Lesion Production

Because tumors are much larger in size compared with the beam width of high-intensity focused ultrasound (HIFU), raster scanning throughout the entire target is conventionally performed for HIFU thermal ablation. Thermal diffusion affects the temperature elevation and the consequent lesion formation. As a result, the lesion will grow continuously over the course of HIFU therapy. The purpose of this study was to investigate the influence of scanning pathways on the overall thermal lesion. Two new scanning pathways, spiral scanning from the center to the outside and spiral scanning from the outside to the center, were proposed with the same HIFU parameters (power and exposure time) for each treatment spot. The lesions produced in the gel phantom and bovine liver were compared with those using raster scanning. Although more uniform lesions can be achieved using the new scanning pathways, the produced lesion areas (27.5 ± 12.3 mm 2 and 65.2 ± 9.6 mm 2, respectively) in the gel phantom are significantly smaller ( p < 0.05) than those using raster scanning (92.9 ± 11.8 mm 2). Furthermore, the lesion patterns in the gel phantom and bovine liver were similar to the simulations using temperature and thermal dose-threshold models, respectively. Thermal diffusion, the scanning pathway and the biophysical aspects of the target all play important roles in HIFU lesion production. By selecting the appropriate scanning pathway and varying the parameters as ablation progresses, HIFU therapy can achieve uniform lesions while minimizing the total delivered energy and treatment time.

Visual servoing for a US‐guided therapeutic HIFU system by coagulated lesion tracking: a phantom study

Applying ultrasound (US)-guided high-intensity focused ultrasound (HIFU) therapy for kidney tumours is currently very difficult, due to the unclearly observed tumour area and renal motion induced by human respiration. In this research, we propose new methods by which to track the indistinct tumour area and to compensate the respiratory tumour motion for US-guided HIFU treatment. For tracking indistinct tumour areas, we detect the US speckle change created by HIFU irradiation. In other words, HIFU thermal ablation can coagulate tissue in the tumour area and an intraoperatively created coagulated lesion (CL) is used as a spatial landmark for US visual tracking. Specifically, the condensation algorithm was applied to robust and real-time CL speckle pattern tracking in the sequence of US images. Moreover, biplanar US imaging was used to locate the three-dimensional position of the CL, and a three-actuator system drives the end-effector to compensate for the motion. Finally, we tested the proposed method by using a newly devised phantom model that enables both visual tracking and a thermal response by HIFU irradiation. In the experiment, after generation of the CL in the phantom kidney, the end-effector successfully synchronized with the phantom motion, which was modelled by the captured motion data for the human kidney. The accuracy of the motion compensation was evaluated by the error between the end-effector and the respiratory motion, the RMS error of which was approximately 2 mm. This research shows that a HIFU-induced CL provides a very good landmark for target motion tracking. By using the CL tracking method, target motion compensation can be realized in the US-guided robotic HIFU system.