High-intensity Focused Ultrasound Exposure Research Articles

Histological characterization of HIFU lesions

Background: High intensity focused ultrasound (HIFU) can destroy tissue by thermal ablation which may be accompanied by acoustic cavitation and/or tissue water boiling, but the biological and histological effects of these treatments have not been fully documented. Here, detailed histological analysis over time using well characterized HIFU exposures in in vivo rat livers is described. Methods: Exposures used invoked either (i) thermal, with acoustic cavitation and/or tissue water boiling or (ii) predominantly thermal damage. Cavitation activity was detected using both active and passive methods. Histological assessment involved hematoxylin and eosin (H&E), picrosirius red and immunohistochemical staining. Results: Distinct concentric damage regions were identified after HIFU exposures. The outermost ring showed a red H&E-stained rim that was characterized by hemorrhage. The adjacent inner band appeared white due to increased extracellular spaces. The morphology of the next zone depended on the exposure. Where there was no tissue acoustic cavitation/water boiling, this was the lesion center, in which heat-fixed cells were seen. Where acoustic cavitation/boiling occurred, a centermost zone with irregular holes up to several hundred microns across was seen. Cleaved caspase-3 and Hsp70 staining in the periphery of both types of HIFU exposures was seen within the outermost ring of hemorrhage, where an inflammatory response was also observed. By day 7, a distinct acellular region in the center of the HIFU lesions had been created. Conclusions: These results identify the morphological effects and elucidate the similarities and differences of HIFU-induced thermal lesions in the presence or absence of acoustic cavitation/tissue water boiling.

The Synergistic Effect of High Intensity Focused Ultrasound on In-vitro Remineralization of Tooth Enamel by Calcium Phosphate Ion Clusters.

Remineralization of dental enamel is an important intervention strategy for the treatment of demineralized lesions. Existing approaches have limitations such as failure to adequately reproduce both the ideal structural and mechanical properties of the native tooth. The ability of ultrasound to control and accelerate the crystallization processes has been widely reported. Therefore, a new approach was explored for in-vitro enamel remineralization involving the synergistic effect of high-intensity focused ultrasound (HIFU) coupled with calcium phosphate ion clusters (CPICs). The demineralized enamel was treated with CPICs, with or without subsequent HIFU exposure for different periods (2.5, 5, and 10 min). The specimens were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. The surface hardness and crystallographic properties of the treated specimens were evaluated using Vickers microhardness testing and X-ray diffraction (XRD), respectively. SEM revealed distinct, organized, and well-defined prismatic structures, showing clear evidence of remineralization in the combined CPIC/HIFU treatment groups. AFM further revealed a decrease in the surface roughness values with increasing HIFU exposure time up to 5 min, reflecting the obliteration of interprismatic spaces created during demineralization. The characteristic Raman band at 960 cm-1 associated with the inorganic phase of enamel dominated well in the HIFU-treated specimens. Importantly, microhardness testing further demonstrated that new mineral growth also recovered the mechanical properties of the enamel in the HIFU-exposed groups. Critical to our aspirations for developing this into a clinical process, these results were achieved in only 5 min. HIFU exposure can synergise and significantly accelerate in-vitro enamel remineralization process via calcium phosphate ion clusters. Therefore, this synergistic approach has the potential for use in future clinical interventions.

Flow and heat transfer through a porous tumor during high-intensity focused ultrasound

High-intensity focused ultrasound (HIFU) represents a non-invasive approach for localized treatment, wherein focused ultrasound waves are applied to specific tissues. However, accurately targeting the HIFU ablation area is still a challenge. The difference in the physical properties of the tumor being treated, compared to normal tissue, particularly, porosity, is an essential aspect that may influence the effectiveness of treatment. This study investigated the impact of tumor porosity, acoustic operating frequency, and the tumor acoustic absorption coefficient on fluid flow and temperature distribution in both the porous tumor and surrounding tissue during HIFU exposure using numerical models. Furthermore, the study examined the differences in porosity between normal and tumor tissues and the resulting phenomena. To determine the acoustic pressure, flow velocity, and temperature distributions in the porous tumor during HIFU treatment, researchers have employed numerical modeling to calculate acoustic wave propagation, fluid flow, and heat transfer processes. This study indicates that the maximal temperature increase might not always necessarily occur at the acoustic pressure focus, particularly, if the tumor does have a higher porosity than the neighboring normal tissue. This was because the flowing fluid of the tumor and adjacent tissues had a substantial impact on the strong convection in the focus area. These findings highlight the significance of this study in terms of precisely localizing the HIFU ablation target region and ensuring minimal thermal injury to the surrounding healthy tissue.

Treating methicillin-resistant Staphylococcus aureus (MRSA) bone infection with focused ultrasound combined thermally sensitive liposomes

Objective Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed ‘heat-targeted, on-demand’ antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection. Methods CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat’s femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40–42 °C (∼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses. Results CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at ∼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted. Conclusion HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.

Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation.

This study describes the development of an ultrasound-responsive polymer system that provides on-demand degradation when exposed to high-intensity focused ultrasound (HIFU). Diels-Alder cycloadducts were used to crosslink polycaprolactone (PCL) polymers and underwent a retro Diels-Alder reaction when stimulated with HIFU. Two Diels-Alder polymer compositions were explored to evaluate the link between reverse reaction energy barriers and polymer degradation rates. PCL crosslinked with isosorbide was also used as a non-Diels-Alder-based control polymer. An increase of HIFU exposure time and amplitude correlated with an increase of PCL degradation for Diels-Alder-based polymers. Ultrasound imaging during HIFU allowed for real-time visualization of the on-demand degradation through cavitation-based mechanisms. The temperature surrounding the sample was monitored with a thermocouple during HIFU stimulation; a minimal increase in temperature was observed. PCL polymers were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), optical profilometry, and mechanical testing. PCL degradation byproducts were identified by mass spectrometry, and their cytocompatibility was evaluated in vitro. Overall, this study demonstrated that HIFU is an effective image-guided, external stimulus to control the degradation of Diels-Alder-based PCL polymers on-demand.

Effect of pulse parameters on ablation efficiency in dual-frequency HIFU therapy

High-intensity focused ultrasound (HIFU) has now been widely used to ablate various benign and malignant tumors. But it is still critical to increase the ablation efficiency in many clinical applications. Dual-frequency HIFU has been proven to be more efficient in ablation, but the principle on selecting the pulse parameters in this method remains to be explored. In this study, the in vitro lesion areas under different pulse repetition frequencies (PRFs), duty ratios, and frequency differences were compared, cavitation activity was also monitored during HIFU exposure. The results showed that different pulse parameters caused different types of lesions. In HIFU therapy, those pulse parameters that maximize the thermal effect, reduce heat dissipation and generate sufficient cavitation activities should be considered. But the method of evaluating or predicting the damage by using the cavitation dose is only applicable to mechanical damage.

Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study

Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively.

Zonal pattern of blood flow distribution in the Pliss lymphosarcoma microcirculatory bed caused by single exposure of high-intensity focused ultrasound

Introduction. Cell damage is not the only important mechanism of high-intensity focused ultrasound (HIFU) for cancer therapy; concomitant microcirculation disorders having alterations patterns not studied enough also have high significance. The aim of the study was to analyze perfusion along the tumor perimeter depending on the HIFU exposure. Materials and methods. We used a stand for HIFU therapy (MTL LLC). Mode: 8.2 kW/cm2 intensity at 0.6 mm focal spot at 1.4 MHz, exposure time: 150, 200, 250 and 500 ms. The object of the study is the vascular bed of Pliss lymphosarcoma. Tumor tissue temperature was monitored by a T-8 thermograph (Russia), blood flow was measured by the BLF21 laser Doppler recorder (USA). Results. After HIFU exposure time from 150–250 ms, perfusion was noted to have decreased to 1.06 perfusion units (pf.u) in the central zone (p<0.01) compared to the control, but by the 30 min perfusion has increased to 1.22 pf.un. No signs of perfusion improvement were found in exposure time of 500 ms. In the peripheral zone, against the background of a decrease in blood flow to 3.6 pf. u. (p < 0.05) by 30 min of the experiment, hyperperfusion was restored to 5.86 pf. u. in all exposure time. In the central zone, a sharp decrease in microcirculation was observed, probably caused by damage of blood vessels; in the periphery of the tumor, perfusion changes had a phasic and reversible pattern. Conclusion. An increase of HIFU exposure correlates with an increase of temperature of Pliss lymphosarcoma tissue near the focus of exposure. Specific perfusion changes are recorded in the central and peripheral zones of the tumor when single exposed to HIFU with different time exposure; the severity of changes depends on ultrasound exposure-time and is characterized by a zonal pattern of blood flow distribution due to the formation of zones of irreversible and reversible damage to microcirculation.

Adaptive singular value decomposition filtering of high-intensity focused ultrasound interference enables real-time ultrasound-guided therapy

High-intensity focused ultrasound (HIFU) is an emerging therapeutic tool for the effective thermal ablation of pathological tissue. For accurate localization of the target and safe control of the HIFU dosage, real-time imaging guidance during the HIFU exposure is desired. Ultrasound imaging has the capability to guide clinicians toward a lesion in real time, but is not an ideal option, as HIFU application causes strong interference, thereby substantially distorting the images used for guidance. Thus, this study introduces singular value decomposition-based filtering capable of restoring ultrasound harmonic images from HIFU interference without undesirable spectral distortion. The results were experimentally validated with a custom-made phantom, indicating that this approach effectively eliminates HIFU-induced artifacts, which is essential for real-time monitoring of the therapeutic process.

Detection of HIFU lesions by optical coherence tomography

The use of high-intensity focused ultrasound (HIFU) to induce irreversible changes in tissue due to heating is well established. We have shown that changes in tissue optical properties (scattering and absorption coefficients) could be used as a proxy to improve sensing and imaging of HIFU lesion formation, as an alternative to conventional methods such as thermometry. Optical coherence tomography (OCT) is a non-invasive optical imaging method which relies on low-coherence interferometry to determine the depth of individual scattering centres within the tissue. Previous studies have demonstrated that OCT signals are sensitive to morphological changes in heated tissue, likely due to denaturation of proteins concomitant with formation of crosslinked structures. The goal of this study was to assess the use of OCT for sensing and imaging HIFU lesions. We demonstrate the feasibility of imaging near-surface lesions in ex vivo chicken breast tissue exposed to HIFU. This technique has potential for detecting changes in optical properties corresponding to the progression of surface lesion formation which are antecedents of skin burn during HIFU exposures, thereby increasing safety and reducing treatment times.

Optically excited nanoparticle enhanced high intensity focused ultrasound therapy of in vivo cancer models

The use of plasmonic gold nanoparticles (AuNP) that have been actively targeted to a specific tumour region is a highly active area of research for both drug delivery and hypothermia applications. One application is providing in situ cavitation nuclei for enhancing high intensity focused ultrasound (HIFU) ablation. When the nanoparticles are simultaneously exposed to HIFU and pulsed laser illumination, microscopic vapour bubbles form providing a controllable way to nucleate cavitation. Using an EGFR-expressing head and neck xenograft model, the biodistribution of targeted and untargeted AuNPs were examined using multispectral, whole body photoacoustic imaging, and inductively coupled plasma mass spectrometry (ICP-MS) analysis following systemic or intratumoral injections. Systemic delivery showed negligible concentration of AuNRs in the tumour; however, intratumoral injection increased its concentration, but remained in the tumour at high concentration for the first 48hrs. Evaluation of ablation performance was undertaken using the same tumour model. An intratumoural injection of untargeted particles, with single 10 s continuous wave HIFU exposures for peak positive/negative pressures of 2.4/2.0 MPa, with simultaneous illumination of 1064 nm pulsed laser light with a surface energy density of 70 mJ/cm2. Post treatment tumour volume was monitored using high frequency ultrasound imaging and calliper measurements, to evaluate exposure efficacy.

Noise reduction technique using deep learning for ultrasound imaging during high-intensity focused ultrasound treatment

One of the problems with ultrasound imaging during high-intensity focused ultrasound (HIFU) treatment is that the therapeutic ultrasound components interfere with the diagnostic ultrasound components, making it impossible to monitor the tissue changes during HIFU exposure. In this study, a convolutional neural network (CNN) framework was applied to the reconstructed ultrasound images with HIFU noise to remove the therapeutic ultrasound components while the diagnostic ultrasound components remain intact. In the experiments, the chicken breast was used as a tissue sample and exposed to HIFU in the water tank. The ultrasound images with and without noise were acquired during an intermission period of HIFU exposure and the noise-reduced images was predicted using the proposed multi-layer regression CNN model through the training process. As a result, ultrasound images with sufficient spatial resolution to detect the thermal lesion were acquired.

Fast and Large Extracorporeal HIFU Ablations of the Liver Using a Toroidal Transducer. Preclinical Study in an in vivo Porcine Model

Introduction: High intensity focused ultrasound (HIFU) is a recent, non-ionizing and non-invasive technology of focal destruction. Extra-corporeal approach is limited by targeting difficulties (bone interface and respiratory motion of the liver) and long-time treatment. We developed a new HIFU transducer based on toroidal geometry and assessed its efficacy on a porcine model. Method: The diameter and the radius of curvature of the toroidal transducer were 70 mm. The operating frequency was 2.5 MHz. An ultrasound imaging probe operating at 7.5 MHz was placed in the center of the HIFU transducer. In vivo experiments were conducted in eleven animals that were followed over 7 days after HIFU exposure. The HIFU exposure lasted about 40 seconds at an acoustic power of 140W. The toroidal device was hand held. Results: The thickness of intervening tissues was measured before each HIFU exposure and was on average 14.9±2.0 mm. The delivered acoustic energy was between 3870 to 7000 J according to the thickness and attenuation of intervening tissues. The dimensions of the HIFU ablations were 21.2±6.0 mm long by 14.7±5.3 mm large. HIFU ablations were visible on ultrasound images, transcutaneously and intra-operatively. No skin burns were observed. No post-operative complication occurred. Conclusions: A non-invasive HIFU treatment of the liver performed with a toroidal transducer is safe, feasible and well tolerated. Large volumes of ablation were obtained in 40s without resorting to mechanical scanning. Treatment parameters are strongly dependent to the thickness and to the attenuation of intervening tissues.

A visualization method for a wide range of rising temperature induced by high-intensity focused ultrasound using a tissue-mimicking phantom

Purpose High-intensity focused ultrasound (HIFU) treatment requires prior evaluation of the HIFU transducer output. A method using micro-capsulated thermochromic liquid crystal (MTLC) to evaluate the temperature distribution in the media during HIFU exposure has been previously developed. However, the color-coded temperature range of commercial MTLC is approximately 10 °C, which is insufficient for temperature measurement for HIFU exposure. We created two layers of tissue-mimicking phantoms with different color-coded temperature ranges, and a new visualization method was developed by utilizing the axisymmetric pressure distribution of a HIFU focus. Methods A two-layer phantom with two sensitivity ranges was created. The HIFU transducer was set to align the focal point to the boundary between the two layers. Images of the upper and lower layers were flipped along the boundary between the two layers such that they overlapped with each other, assuming the pressure distribution of HIFU to be axisymmetric. Results The experimental and simulation results were compared to evaluate the accuracy of the phantom temperature measurement. The experimental time profile of the temperature and spatial distribution around the HIFU focus matched well with that of the simulation. However, there is room for improvement in the accuracy in the axial direction of HIFU focus. Conclusion Users can apply our proposed method in clinical practice to promptly assess the output of the HIFU transducer before treatment.

Numerical Study of Bubble Cloud and Thermal Lesion Evolution During Acoustic Droplet Vaporization Enhanced HIFU Treatment.

Acoustic droplet vaporization (ADV) has been proven to enhance high intensity focused ultrasound (HIFU) thermal ablation of tumor. It has also been demonstrated that triggering droplets before HIFU exposure could be a potential way to control both the size and the shape of the thermal lesion. In this paper, a numerical model is proposed to predict the thermal lesion created in ADV enhanced HIFU treatment. Bubble oscillation was coupled into a viscoelastic medium in the model to more closely represent real applications in tissues. Several physical processes caused by continuous wave ultrasound and elevated temperature during the HIFU exposure were considered, including rectified diffusion, gas solubility variation with temperature in the medium, and boiling. Four droplet concentrations spanning two orders of magnitude were calculated. The bubble cloud formed from triggering of the droplets by the pulse wave ultrasound, along with the evolution of the shape and location of the bubble cloud and thermal lesion during the following continuous wave exposure was obtained. The increase of bubble void fraction caused by continuous wave exposure was found to be consistent with the experimental observation. With the increase of droplet concentration, the predicted bubble cloud shapes vary from tadpole to triangular and double triangular, while the thermal lesions move toward the transducer. The results show that the assumptions used in this model increased the accuracy of the results. This model may be used for parametrical study of ADV enhanced HIFU treatment and be further used for treatment planning and optimization in the future.

Effect of ultrasonic intensity and intervals of ultrasonic exposure on efficiency of sonochemiluminescence in gel phantom for sonodynamic therapy

Sonodynamic treatment (SDT) is one of the non-invasive modalities for cancer treatment. In SDT, ultrasound, reactive oxygen species (ROS) generated from cavitation bubbles, and a sonosensitizer are used in combination. In this study, high-intensity focused ultrasound (HIFU) was employed as ultrasound to generate and oscillate cavitation bubbles. When cavitation bubbles oscillate and collapse, the gas inside the bubble is extremely compressed and heated, inducing ROS generation. The disadvantage of SDT is a long treatment time because of its smallness of a treatment region by a shot of HIFU. To overcome this, the effect of the intensity and interval of HIFU for oscillating cavitation bubbles was investigated by using luminol sonochemiluminescence and high-speed imaging. The results showed that a HIFU exposure sequence with an interval of 300 ms and a burst-wave intensity of 0.25 kW cm−2 improve the energy efficiency of ROS generation.

The feasibility of a noise elimination method using continuous wave response of therapeutic ultrasound signals for ultrasonic monitoring of high-intensity focused ultrasound treatment

PurposeIn this study, the robustness and feasibility of a noise elimination method using continuous wave response of therapeutic ultrasound signals were investigated when tissue samples were moved to simulate the respiration-induced movements of the different organs during actual high-intensity focused ultrasound (HIFU) treatment. In addition to that, the failure conditions of the proposed algorithm were also investigated.MethodsThe proposed method was applied to cases where tissue samples were moved along both the lateral and axial directions of the HIFU transducer to simulate respiration-induced motions during HIFU treatment, and the noise reduction level was investigated. In this experiment, the speed of movement was increased from 10 to 40 mm/s to simulate the actual movement of the tissue during HIFU exposure, with the intensity and driving frequency of HIFU set to 1.0–5.0 kW/cm2 and 1.67 MHz, respectively. To investigate the failure conditions of the proposed algorithm, the proposed method was applied with the HIFU focus located at the boundary between the phantom and water to easily cause cavitation bubbles. The intensity of HIFU was set to 10 kW/cm2.ResultsAlmost all HIFU noise was constantly able to be eliminated using the proposed method when the phantom was moved along the lateral and axial directions during HIFU exposure. The noise reduction level (PRL in this study) at an intensity of 1.0, 3.0, and 5.0 kW/cm2 was in the range of 28–32, 38–40, and 42–45 dB, respectively. On the other hand, HIFU noise was not basically eliminated during HIFU exposure after applying the proposed method in the case of cavitation generation at the HIFU focus.ConclusionsThe proposed method can be applicable even if homogeneous tissues or organs move axially or laterally to the direction of HIFU exposure because of breathing. A condition under which the proposed algorithm failed was when instantaneous tissue changes such as cavitation bubble generation occurred in the tissue, at which time the reflected continuous wave response became less steady.

Phase-shift Perfluoropentane Nanoemulsions Enhance Pulsed High-intensity Focused Ultrasound Ablation in an Isolated Perfused Liver System and Their Potential Value for Cancer Therapy.

To investigate whether phase-shift perfluoropetane (PFP) nanoemulsions can enhance pulsed high-intensity focused ultrasound (HIFU) ablation. PFP was encapsulated by poly(lactic-co-glycolic acid) (PLGA) to form a nanometer-sized droplet (PLGA-PFP), which was added to an isolated perfused liver system. Meanwhile, phosphate-buffered saline (PBS) was used as a control. The perfused liver was exposed to HIFU (150 W, t=3/5/10 s) at various duty cycles (DCs). The ultrasound images, cavitation emissions, and temperature were recorded. Rabbits with subcutaneous VX2 tumors were exposed to HIFU (150 W) at various DCs with or without PLGA-PFP. After ablation, necrosis volume and energy efficiency factor were calculated. Pathologic characteristics were observed. Compared to the PBS control, PLGA-PFP nanoemulsions markedly enhanced HIFU-induced necrosis volume in both perfused livers and subcutaneous VX2 tumor-bearing rabbits (P <.05). Inertial cavitation was much stronger in the pulsed-HIFU exposure at 10% than that in the continuous-wave HIFU exposure (P <.01). Peak temperature at 100% DC was significantly higher than that at 10% (P <.05). Compared to 100% DC HIFU exposure, the mean necrosis volume induced by 10 s exposure at 50% DC was significantly larger (P <.005) but lower at 10% DC in the isolated perfused livers (P <.05). In addition, the mean necrosis volume in subcutaneous VX2 tumor-bearing rabbits was significantly increased after HIFU exposure at 10% DC when compared to those at 100% DC (P <.05). Histopathologic analysis showed liquefaction necrosis in pulsed HIFU. PLGA-PFP nanoemulsions can enhance HIFU ablation in the isolated perfused livers and promote tumor ablation in the subcutaneous xenograft rabbit model. Appropriate pulsed HIFU exposure may increase the necrosis volume and reduce total ultrasound energy required for HIFU ablation.

Investigation of feasibility of noise suppression method for cavitation-enhanced high-intensity focused ultrasound treatment

In high-intensity focused ultrasound (HIFU) treatment, a method that monitors tissue changes while irradiating therapeutic ultrasound is needed to detect changes in the order of milliseconds due to thermal coagulation and the presence of cavitation bubbles. The new filtering method in which only the HIFU noise was reduced while the tissue signals remained intact was proposed in the conventional HIFU exposure in our preliminary study. However, HIFU was irradiated perpendicular to the direction of the imaging ultrasound in the preliminary experiment, which was believed to be impractical. This study investigated the efficacy of the proposed method a parallel setup, in which both HIFU and imaging beams have the same axis just as in a practical application. In addition, this filtering algorithm was applied to the “Trigger HIFU” sequence in which ultrasound-induced cavitation bubbles were generated in the HIFU focal region to enhance heating. In this setup and sequence, HIFU noise level was increased and the summation or difference tone induced by the interaction of HIFU waves with the imaging pulse has the potential to affect this proposed method. Ex-vivo experiments proved that the HIFU noise was selectively eliminated by the proposed filtering method in which chaotic acoustic signals were emitted by the cavitation bubbles at the HIFU focus. These results suggest that the proposed method was practically efficient for monitoring tissue changes in HIFU-induced cavitation bubbles.

Fuzzy Logic Control-Based HIFU System Integrated with Photoacoustic Imaging Module for Ex Vivo Artificial Tumor Treatment

The objective of this study is to design a therapeutic method combining a portable high intensity focused ultrasound (HIFU) design which is suitable for the laboratory environment and a tailored integrated photo-acoustic imaging (PAI) system for monitoring thermal treatment. The electrical HIFU design is fabricated with changeable operating frequency and justified output power for resonating with different kinds of commercial transducers. The system’s control interface is built based on a touch screen to create a companionable interaction for users. The embedded fuzzy logic controller using the thermal input from the thermocouple sensor precisely drives the target temperature during HIFU exposure to achieve the expectedly coagulating results. The PAI system with 532-nm laser excitation is also integrated to define the affected region before and after HIFU treatment. The proposed fuzzy controller-integrated HIFU setup compatible with the PAI system is a feasible instrument in thermal therapy for ex vivo artificial tumors management.