High-intensity Focused Ultrasound Sonication Research Articles

An improved scheme for passive cavitation imaging in high intensity focused ultrasound

Passive cavitation imaging (PCI) is an effective technique for monitoring high intensity focused ultrasound (HIFU) procedure due to the correlation between cavitation activities and the therapeutic effects. Nevertheless, current PCI techniques are unable to recognize noise signals from non-cavitation situations, and they fail to accurately visualize the highly dynamic cavitation activities due to the lack of a stable baseline reference. In this study, a deep learning-based cavitation detection network (CD-NET) was proposed to determine whether passively received channel signals originated from cavitation activities or were merely noises. Additionally, a cavitation intensity baseline was derived to better display the drastically time-varying cavitation activities. The CD-NET model was trained and validated with data collected from in-vitro and ex-vivo HIFU sonication experiments, and then tested by in-vivo rabbit experiments. Both CD-NET models, trained with data from the in-vitro agar phantoms and ex-vivo bovine liver tissues, successfully distinguished between cavitation and non-cavitation activities from the same study object, achieving accuracies as high as 99.7% and 99.5%, respectively. In addition, the models trained on in-vitro and ex-vivo datasets achieved accuracies of 88.1% and 91.4%, respectively, when detecting cavitation events from unseen in-vivo data. The results demonstrate that the improved PCI scheme, utilizing the CD-NET model and a data-derived cavitation baseline, is resistant to noise from non-cavitation situations and can depict the dynamic characteristics of cavitation more reliably. In conclusion, this study addressed two practical challenges in PCI techniques, allowing for better monitoring of cavitation-related HIFU sonication in clinical applications.

Microbubble-enhanced HIFU therapy for vascularized tumors using Levovist contrast agent

High-intensity focused ultrasound (HIFU) has enormous potential in the treatment of cancers; however, there is still plenty of challenges associated with using acoustic energy to treat vascularized tumors. Among them, the blood flow cooling reduces the treatment efficiency significantly and results in a long treatment period. Various studies have shown that the HIFU improves cancer treatment by targeting the cancer tissue. Unfortunately, the issues related to vascularization have remained unsolved. In the present study, through a novel approach, a promising strategy is proposed by injecting Levovist contrast agent solution in the vascularized tumor. The complicated interaction between the Levovist microbubble (MB) and the ultrasonic waves is innovatively modeled by considering the coupled effect of HIFU wave propagation, fluid flow, MB oscillations, and transient heat transfer for a multi-layered porous model of liver tumor. The proposed strategy is evaluated in terms of the extent of irreversible TD and treatment duration. The results reflect the role of MB oscillation on the temperature rise, as injection of a 2 μm-MB during 15 s of HIFU sonication increases the temperature by 9.61% compared to no-MB condition. Meanwhile, the MB oscillation advances the irreversible damage, and tumor cells undergo thermal ablation by 48.94% earlier than the case with no-MB agent. Additionally, it is found that the MB size has a substantial effect on the amount of heat deposition. At an operating condition of 1.25 MHz and 10 W, the viscous power deposition for a 2 μm-MB is3.81 mW, while for a 50 μm-MB, it is reduced to 0.96 mW. On the contrary, the heat source due to the secondary acoustic power deposition is proportional to the MB size, as it increases from 60.5 mW for a 2 μm-MB to 180 mW for a 50 μm-MB, demonstrating a 2.97-fold increase. Eventually, an assessment of the extent of the necrotic area shows an increase at all frequencies by injecting an MB into the tumor area. At an operating condition of 1.5 MHz, oscillation of 2 μm-MB expands the necrotic area by 4.01% compared to the no-MB condition. Based on the obtained results, the injection of Levovist contrast agent solution in the vascularized tumor can be regarded as an effective method for reducing the treatment time and avoiding several sonication.

Ultrasound controlled mechanophore activation in hydrogels for cancer therapy

Mechanophores are molecular motifs that respond to mechanical perturbance with targeted chemical reactions toward desirable changes in material properties. A large variety of mechanophores have been investigated, with applications focusing on functional materials, such as strain/stress sensors, nanolithography, and self-healing polymers, among others. The responses of engineered mechanophores, such as light emittance, change in fluorescence, and generation of free radicals (FRs), have potential for bioimaging and therapy. However, the biomedical applications of mechanophores are not well explored. Herein, we report an invitro demonstration of an FR-generating mechanophore embedded in biocompatible hydrogels for noninvasive cancer therapy. Controlled by high-intensity focused ultrasound (HIFU), a clinically proven therapeutic technique, mechanophores were activated with spatiotemporal precision to generate FRs that converted to reactive oxygen species (ROS) to effectively kill tumor cells. The mechanophore hydrogels exhibited no cytotoxicity under physiological conditions. Upon activation with HIFU sonication, the therapeutic efficacies in killing invitro murine melanoma and breast cancer tumor cells were comparable with lethal doses of H2O2 This process demonstrated the potential for mechanophore-integrated HIFU combination as a noninvasive cancer treatment platform, named "mechanochemical dynamic therapy" (MDT). MDT has two distinct advantages over other noninvasive cancer treatments, such as photodynamic therapy (PDT) and sonodynamic therapy (SDT). 1) MDT is ultrasound based, with larger penetration depth than PDT. 2) MDT does not rely on sonosensitizers or the acoustic cavitation effect, both of which are necessary for SDT. Taking advantage of the strengths of mechanophores and HIFU, MDT can provide noninvasive treatments for diverse cancer types.

Clinical outcome of high-intensity focused ultrasound as the preoperative management of cesarean scar pregnancy

ObjectiveThe aim of this study was to retrospectively evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) treatment as the preoperative management of cesarean scar pregnancy (CSP). Materials and methods225 patients with definite Type I CSP were treated with suction curettage under hysteroscopic guidance. Among them, 103 patients chose HIFU treatment before hysteroscopy (assign to the HIFU group), and the other 122 patients without any pretreatment before hysteroscopy to the control group. The successful rate, volume of intraoperative blood loss, time for serum β-human chorionic gonadotropin (β-hCG) level returned to normal, gestational sac disappeared, normal menstrual recovery, and adverse effects were collected and analyzed to compare the two approaches. ResultsThe successful rate (98.06%) in the HIFU group was higher than that (91.80%) in the contrast group. The median ablation time was 39 min and the median HIFU sonication time was 106.6 s. The median volume of intraoperative blood loss in the HIFU group was lower than that in the contrast group (P < 0.001), and the median time of gestational sac disappeared in the HIFU group was shorter than that in the contrast group. There were no statistically significant differences in the time of serum β-hCG returned to normal and days of menstrual recovery between the 2 groups. ConclusionBased on our results, it appears that HIFU ablation is a safe and effective modality as pre-treatment before hysteroscopy in the management of CSP.

Analytical and Numerical Model of High Intensity Focused Ultrasound Enhanced With Nanoparticles.

High intensity focused ultrasound (HIFU) is a new noninvasive therapeutics that allows local treatment of solid tumors through a hyperthermal mechanism using ultrasonic energy. One promising strategy to increase the thermal efficiency of HIFU is to employ nanoparticles (NPs) as ultrasound agents for the hyperthermia procedure. However, the interaction mechanism between NPs and ultrasonic waves has not been well understood. In an effort to investigate the heating process of NPs-enhanced HIFU, we derived a set of HIFU equations governing the temperature variation during the thermal ablation based on the principle of conservation of energy for heat transfer mechanism. A numerical model was developed to solve the HIFU equations to simulate the absorption mechanism of HIFU in the presence of NPs, the consequent heat transfer process, and the temperature rise profile during the sonication period. The accuracy of numerical model was verified by performing a series of experiments on tissue-mimicking phantoms embedded with magnetic NPs (MNPs). The transport processes taking place at the boundaries between NPs and surrounding medium played the major role in the temperature rise during HIFU sonication. Besides, the effects of MNPs on rising temperature were improved by amplifying the ultrasonic power and frequency as well as by increasing the MNP concentration. A quantitative comparison with experimental results demonstrated the potential of the numerical model to accurately predict the heating mechanism of HIFU mediated by NPs. The proposed method can help with simulation of HIFU when NPs are employed as ultrasound agents.

Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

AbstractCell‐based drug delivery systems are a promising platform for tumor‐targeted therapy due to their high drug‐loading capacities and inherent tumor‐homing abilities. However, the real‐time tracking of these carrier cells and controlled release of the encapsulated drugs are still challenging. Here, ultrasound‐activatable cell bombs are developed by encapsulating doxorubicin (DOX) and phase transformable perfluoropentane (PFP) into hollow mesoporous organosilica nanoparticles (HMONs) to prepare DOX/PFP‐loaded HMONs (DPH), followed by internalization into macrophages (RAW 264.7 cells). The resulting cell bombs (DPH‐RAWs) can maintain viability and actively home to the tumor. Especially, their migration can be tracked in real time using ultrasound due to the vaporization of a small portion of PFP during cell incubation at 37 °C. After accumulation at the tumor site, the further vaporization of remaining PFP can be triggered by a short‐pulsed high intensity focused ultrasound (HIFU) sonication, resulting in the generation of several large microbubbles, which destroys DPH‐RAWs and allows drug release out of these cells. The DPH‐RAWs combined with short‐pulsed HIFU sonication significantly inhibit tumor growth and prolong survival of tumor‐bearing mice. In conclusion, this study provides a new approach to cell‐based drug delivery systems for real‐time tracking of their migration and targeted cancer treatment.

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

BackgroundTemperature 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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.

Clinical Usefulness of the Microbubble Contrast Agent SonoVue in Enhancing the Effects of High-Intensity Focused Ultrasound for the Treatment of Adenomyosis.

To evaluate the clinical usefulness of the microbubble contrast agent SonoVue in enhancing high-intensity focused ultrasound (HIFU) for the treatment of adenomyosis. A total of 102 patients with adenomyosis, assessed from August 2015 to April 2017, were randomly divided into 1-minute (A) and 10-minute (B) groups, respectively. In groups A and B, HIFU started 1 minute and 10 minutes, respectively, after SonoVue injection. All patients underwent a magnetic resonance imaging scan before and after HIFU treatment. The occurrence rates of massive gray scale change, nonperfused volume, and fractional ablation were similar in both groups (P > .05). Meanwhile, sonication time to massive gray scale change was reduced in group A compared with group B (P < .05). In addition, mean power, total energy, and energy efficiency factor were lower in group A than group B (all P < .05). The incidence rates of most perioperative and all postoperative adverse events were similar in both groups (P > .05). The incidence rates of pain in the treated region, leg pain, and sciatic or buttock pain during HIFU were substantially lower in group A than group B (P < .05). Overall, starting HIFU sonication at 1 minute after SonoVue injection enhances HIFU ablation by cavitation and heating and is safe. Early massive gray scale change, lower total energy, and reduced mean power are potential safety factors.

Effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound for uterine fibroids: a randomised controlled trial

Objective: To investigate the effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound (HIFU) treatment of uterine fibroids.Methods: A total of 120 patients with solitary uterine fibroid were randomly assigned into Groups A, B, C and D. Patients in Groups A and B received 1.5 ml of SonoVue, Groups C and D received 1.5 ml of saline before HIFU ablation. HIFU sonication started at 6 min after administration of SonoVue or saline in Groups A and C, whereas it started at 10 min in Groups B and D. On day 1 after HIFU, magnetic resonance imaging was performed. Patients were followed up via phone or clinic visit during the first week after HIFU.Results: No significant difference was observed in terms of age, fibroid location, diameter of fibroids, signal intensity on T2-weighted imaging, or tumour volume among the four groups (p > 0.05). The use of SonoVue significantly shortened the treatment time and sonication time. The sonication start time of 6 min, relative to 10 min, had significant effects on the treatment time and sonication time. The use of intravenous SonoVue followed by HIFU ablation 6 min later significantly increased the rate of significant grey-scale changes (55.9%) and the non-perfused volume ratio (94.2% ± 10.6%). No significant differences were observed in the incidence of intra-procedure and post-HIFU adverse effects among the four groups (p > 0.05).Conclusions: SonoVue could be safely used to enhance the ablation effects of HIFU treatment of uterine fibroids.

An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models.

Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU can reversibly block the conduction of peripheral nerves without damaging the nerves while using an appropriate ultrasonic parameter. Temporary and partial block of the action potentials of nerves shows that HIFU has the potential to be a useful clinical treatment for pain relief. This work demonstrates the procedures for suppressing the action potentials of neuropathic nerves in diabetic rats in vivo using an HIFU transducer. The first step is to generate adult male diabetic neuropathic rats by streptozotocin (STZ) injection. The second step is to evaluate the peripheral diabetic neuropathy in STZ-induced diabetic rats by an electronic von Frey probe and a hot plate. The final step is to record in vivo extracellular action potentials of the nerve exposed to HIFU sonication. The method showed here may benefit the study of ultrasound analgesic applications.

Enhancing ablation effects of a microbubble contrast agent on high-intensity focused ultrasound: an experimental and clinical study.

To investigate the relationship between SonoVue ablation enhancement effects on high-intensity focused ultrasound (HIFU) and the concentration of SonoVue and timing of HIFU. Two randomisedcontrolledtrials. Ananimal centre in a university and a gynaecological department in a university hospital in China. 63 rabbits and 143 patients with a solitary uterine fibroid. Among the 63 rabbits, three were assigned to the control group. The other 60were evenly assigned to three study groups pretreated with 0.03, 0.05 or 0.07ml/kg of SonoVue before HIFU treatment. Two points in each liver were selected to be treated with HIFU and sonication started at 10, 30, 60, 90, 120, 150, 180, 210, 250 or 300seconds after the administration of SonoVue, respectively. The 143 patients with solitary uterine fibroids were assigned to four groups: 30 patients were treated using only HIFU; the other patients were pretreated with same dosage of SonoVue and 32, 38 and 43 were treated with HIFU at 1-, 3-, and 5-minutes after administration of SonoVue, respectively. The relation between SonoVue ablation enhancement effects on HIFU and the concentration of SonoVue and timing of HIFU. In the experimental study, the highest temperature and the largest necrotic volume in the liver were observed when HIFU sonication started at 60seconds after administration of SonoVue. In the clinical study, the rate of significant grey-scale changes in the 1-minute SonoVue group was significantly greater than in the other three groups. The sonication time to reach massive grey-scale changes measured in the 1-minute SonoVue group was significantly shorter than in in the other three groups. The sonication time for ablating 1cm3 of fibroid volume in the 1-minute SonoVue group was significantly shorter than in the other three groups. The acoustic energy used in treating 1mm3 of uterine fibroid in the 1-minute SonoVue group was significantly less than that used in the other three groups. No major complications occurred in this study. SonoVue could safely be used to enhance the ablation effects of HIFU treatment, and the optimal time to begin HIFU sonication seems to be 1minute after the administration of SonoVue. SonoVue, a microbubble contrast agent, enhanced the ablation effects of HIFU treatment; the optimal time to begin HIFU sonication appears to be 1minute after the administration of SonoVue.

Improved intercostal HIFU ablation using a phased array transducer based on Fermat's spiral and Voronoi tessellation: A numerical evaluation

A major complication for abdominal High Intensity Focused Ultrasound (HIFU) applications is the obstruction of the acoustic beam path by the thoracic cage, which absorbs and reflects the ultrasonic energy leading to undesired overheating of healthy tissues in the pre-focal area. Prior work has investigated the determination of optimized transducer apodization laws, which allow for a reduced rib exposure whilst (partially) restoring focal point intensity through power compensation. Although such methods provide an excellent means of reducing rib exposure, they generally increase the local energy density in the pre-focal area, which similarly can lead to undesired overheating. Therefore, this numerical study aimed at evaluating whether a novel transducer design could provide improvement for intercostal HIFU applications, in particular with respect to the pre-focal area. A combination of acoustic and thermal simulations was used to evaluate 2 mono-element transducers, 2 clinical phased array transducers, and 4 novel transducers based on Fermat's Spiral (FS), two of which were Voronoi-tessellated (VTFS). Binary apodizations were determined for the phased array transducers using a collision detection algorithm. A tissue geometry was modeled to represent an intercostal HIFU sonication in the liver at 30 and 50 mm behind the ribs, including subsequent layers of gel pad, skin, subcutaneous fat, muscle, and liver tissue. Acoustic simulations were then conducted using propagation of the angular spectrum of plane waves (ASPW). The results of these simulations were used to evaluate pre-focal intensity levels. Subsequently, a finite difference scheme based on the Pennes bioheat equation was used for thermal simulations. The results of these simulations were used to calculate both the energy density in the pre-focal skin, fat, and muscle layers, as well as the energy exposure of the ribs. The acoustic simulations showed that for a sonication in a single point without beamsteering, comparing the best performing clinical phased array in this study to an equivalent VTFS transducer, the maximum intensity in the focal point was increased from 19.0 to 27.0 W/mm2 for the sonication 30 mm behind the ribs, while the rib area exposed to ≥20 J/cm2 was reduced from 0.88 to 0.14 cm2 . For the sonication 50 mm behind the ribs, the maximum focal point intensity was increased from 13.4 to 21.5 W/mm2 , while the rib area exposed to ≥40 J/cm2 was lowered from 2.71 to 0.01 cm2 . The thermal simulations showed that for a circular sonication cell of 4 mm diameter in the transversal plane, sonication times for sonications 30/50 mm behind the ribs were reduced from 13.9 to 8.38 s/38.2 to 17.4 s, respectively. Energy density levels in the skin for these sonications were decreased from 5.28 to 2.22/9.45 to 3.78 J/mm2 . VTFS transducers are expected to provide improvement for intercostal HIFU applications compared to currently available clinical transducers, as they reduce both the energy density in the pre-focal zone and the energy exposure of the ribs. These characteristics allow for increasing either the re-sonication rate or the treatment volume per sonication.

Real-time feedback control for high-intensity focused ultrasound system using localized motion imaging

High-intensity focused ultrasound (HIFU) is one of the noninvasive treatment for tumors. Visualizing the treated area inside the human body is necessary to control the HIFU exposure. Localized motion imaging (LMI) using ultrasound to induce and detect tissue deformation is one technique to detect a change in tissue stiffness caused by thermal coagulation. In experiments with porcine liver, LMI has shown to detect deformation with less than 20% accuracy. We have developed a prototype feedback control system using real-time LMI. In this system, coagulation size was measured every 1 s and controlled to correspond to a targeted size. The typical size error was reduced to 14% from 35%. LMI displacements in normal and coagulated tissues were sufficiently different to discriminate between coagulated areas and noncoagulated ones after HIFU sonication and to visualize treated areas after HIFU treatment.

Influence of water and fat heterogeneity on fat-referenced MR thermometry.

To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. The sphere experiment showed susceptibility-related errors of 8.4 °C and 0.2 °C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37 °C was 47.2 ± 21.6 °C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7 °C) yielded a maximum temperature error of 6.6 °C compared with 2.5 °C without fat referencing. Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors.

Enhanced mechanical damage to in vitro cancer cells by high-intensity-focused ultrasound in the presence of microbubbles and titanium dioxide.

To evaluate in vitro the feasibility of therapeutic high-intensity-focused ultrasound (HIFU) combined with microbubbles and titanium dioxide (TiO2). Oral squamous cell carcinoma cells (HSC-2) were sonicated using a HIFU transducer with a resonant frequency of 3.5 MHz, 30 mm in diameter, and focal length of 50 mm. The ultrasound intensity was 210 W/cm(2), and two pulses (0.5 s each) were sonicated for each cell sample (9 × 10(4) cells per well). Immediately after HIFU, the viable cells were measured by an automated cell counter. The survival rate was measured in the presence of microbubbles (Sonazoid) and peroxo titania-silica (R-P-TS) or anatase titania-silica (R-A-TS) TiO2. Cell viability immediately following sonication in the presence of TiO2 (R-A-TS) and TiO2 (R-P-TS) was 65.5 ± 0.7 and 59.4 ± 3.3 %, respectively. A marked decrease in cell viability was seen when microbubbles were added to the above cell conditions. Specifically, cell viability decreased to 14.0 ± 0.1 and 4.4 ± 0.9 % when microbubbles were added to samples containing TiO2 (R-A-TS) and TiO2 (R-P-TS), respectively. Immediate in vitro cell killing was observed with short pulsed duration HIFU sonication with a combination of microbubbles and TiO2. This finding suggests that TiO2 could have caused enhanced mechanical cell destruction by microbubbles.

Nanohybrid liposomal cerasomes with good physiological stability and rapid temperature responsiveness for high intensity focused ultrasound triggered local chemotherapy of cancer.

The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in combination with the component lipids of conventional low temperature sensitive liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm, exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug loaded HTSCs showed much longer blood circulation time (half-life >8.50 ± 1.49 h) than conventional LTSLs (0.92 ± 0.17 h). An in vitro study demonstrated that the drug loaded HTSCs are highly stable at 37 °C and show a burst release at 42 °C, providing a capability to act synergistically against tumors. We found that the HTSCs with a proportion of 43.25% of CFL could release more than 90% hydrophilic drugs in 1 min at an elevated temperature of 42 °C generated by HIFU exposure. After intravenous injection of doxorubicin (DOX) loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited. Therefore, the drug loaded HTSCs combined with HIFU hold great potential for efficient local chemotherapy of cancer due to the ability to deliver high concentration of chemotherapy drugs directly to the tumor, achieve maximum therapeutic efficacy and minimal side effects, and avoid the damage to the healthy tissues caused by systemic administration of drugs.

In Vivo Monitoring of HIFU Induced Temperature Rise in Porcine Liver Using Magnetic Resonance Thermometry1

High intensity focused ultrasound (HIFU) is a noninvasive medical procedure during which a large amount of energy is deposited in a short duration, which causes sudden localized rise in tissue temperature, and ultimately, cell necrosis. In the preclinical characterization of thermal fields generated by HIFU systems, the temperature rise in an ex vivo or an in vivo tissue must be accurately measured. The temperature rise can be measured using thin wire thermocouples or magnetic resonance (MR) thermometry. Among the two methods, thermocouples can be embedded invasively in the animal tissue, and HIFU induced temperature rise can be measured by focusing the beam on the thermocouple junction for the desired sonication time. However, the temperature rise measured using thermocouples is subject to several significant sources of error. One source of error associated with direct HIFU sonication of thermocouples is viscous-heating artifact [1]. Positioning errors represent another challenge in measuring temperature by locating beam atop a thermocouple [2]. Consequently, it has been difficult to accept that the temperature recorded by the thermocouple is the actual temperature at the focus of the HIFU beam. Therefore, there is a need for a method that can address these limitations. Unlike the measurement of temperature using thermocouples, the MR thermometry is a noninvasive method that does not suffer from the problems of positioning error and thermal artifacts. The magnetic resonance imaging (MRI) scanner is capable of assessing the transient temperature rise across the treatment volume, as well as measuring the volume of the thermal lesion [3]. Although the MR temperature monitoring was used to evaluate the feasibility of MR-guided HIFU ablation in the liver and kidney [4], the effect of higher acoustic powers on initiation of cavitation and possible maximum temperature rise in these organs were not assessed using MR thermometry. In this study, MR thermometry was used to monitor HIFU ablations performed on in vivo porcine livers, at elevated acoustic powers of 10 W, 30 W, and 40 W to assess the temperature field where initiation of cavitation is known to occur. Temperature rise during the heating phase as well as the temperature decay during the cooling phase was acquired. The transient temperature profiles measured during the heating and cooling phases for the three powers were compared, in order to check the HIFU induced maximum temperature rise.

Ablation of Leiomyomas Using a Combination of HIFU and Iodized Oil In Vitro

This study investigates the enhancement effects of iodized oil and the features of hyperechoic focus changes in a target region of high-intensity focused ultrasound (HIFU) ablated uterine fibroids. Leiomyomas in the experimental group of 20 randomly assigned patients were ablated by HIFU under certain parameters 30 min after 1 mL of iodized oil was injected into the center of the myomas. The value of the gray scale and its area were observed by B-mode ultrasound in the target region and were carefully recorded at 0, 2, 4, and 5 min, respectively, after HIFU ablation. The samples were sectioned successively in a thickness of 1∼2 mm and stained by 2,3,5-triphenyltetrazolium chloride solution within 1 h after HIFU ablation. The TTC non-staining volumes were measured afterwards. All procedures in the control group of the other 20 randomly assigned patients were the same except that iodized oil was replaced by physiologic saline. The hyperechoic areas in the target region were observed in all fibroids of both groups. Compared with the control group, the gray scale values in the target region of the experimental group were higher 4 min after HIFU ablation. The enhanced gray scale area in the target region and the 2,3,5-triphenyltetrazolium chloride non-staining volumes in the experimental group were bigger. Based on our experience, HIFU sonication of leiomyomas injected with iodized oil produces hyperechoic foci that are greater than areas injected with saline. More studies are required to understand the clinical implications of these observations.

High intensity focused ultrasound ablation of goat liver in vivo: Pathologic changes of portal vein and the “heat-sink” effect

The purpose of this study was to evaluate pathological changes of the portal vein (PV) and the effects on main branches of the hepatic PV during HIFU (high-intensity focused ultrasound) sonication when liver tissue adjacent to the main branches of hepatic PV was ablated. Normal liver tissue at 0mm, 5mm, 10mm away from the hepatic portal vein in 50 healthy goats was ablated with magnetic resonance image-guided HIFU (MRgHIFU). MRI showed a non-perfusion region at the target area but did not show any significant changes of the PV immediately after HIFU. The histological examination 1day after HIFU showed coagulative necrosis at the target area, revealed deep-dyed swelling collagen (CS) fibers and vessel wall fracture (VWF) in the PV adjacent to the target area; however, no CS or VWF was observed in the PV 1week after HIFU ablation. The energy required to ablate the foci at 0mm was 21% more than that at 10mm from the PV (p<0.05); the energy needed to ablate foci 5mm away from the PV was 10% more than that at 10mm from the PV (p<0.05). We concluded that minor injury of the hepatic portal vein may occur when ablating the adjacent liver tissue, and the acoustic energy deposition is related to the distance to the portal vein.

Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility study ex vivo

Magnetic resonance imaging (MRI) and ultrasonography have been used simultaneously in this ex vivo study for the image-guidance of high intensity focused ultrasound (HIFU) treatment in moving tissue. A ventilator-driven balloon produced periodic and non-rigid (i.e. breathing-like) motion patterns in phantoms. MR-compatible ultrasound (US) imaging enabled near real-time 2D motion tracking based on optical flow detection, while near-harmonic reference-free proton resonance frequency shift (PRFS) MR thermometry (MRT) was used to monitor the thermal buildup on line. Reference-free MRT was applied to gradient-echo echo-planar imaging phase maps acquired at the frame rate of 250 to 300 ms/slice with voxel size 1.25×1.25×5 mm3. The MR-US simultaneous imaging was completely free of mutual interferences while minor RF interferences from the HIFU device were detected in the far field of the US images. The effective duty-cycle of the HIFU sonication was close to 100 % and no off-interval was required to temporally decouple it from the ultrasonography. The motion compensation of the HIFU sonication was achieved with an 8 Hz frame rate and sub-millimeter spatial accuracy, both for single-focus mode and for an iterated multi-foci line scan. Near harmonic reference-less PRFS MRT delivered motion-robust thermal maps perpendicular or parallel to the HIFU beam (0.7 °C precision, 0.5 °C absolute accuracy). Out-of-plane motion compensation was not addressed in this study.