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The purpose of this study was to evaluate the feasibility of high intensity focused ultrasound (HIFU) for ultrasonic treatment of biological tissues, particularly, for hemostasis of deep arterial bleeding. The results of designing, modeling and evaluation of an ultrasound applicator capable of creating thermal lesions in the arterial vessels were presented. New effective HIFU transducers designs and ultrasonic methods for stopping deep arterial bleeding were developed and estimated. Mathematical modeling of the HIFU transducers and acoustic fields were performed. The experiments were made on acoustic vascular phantoms as well as on lamb's femoral artery at a standard protocol. During ultrasound exposure, arterial blood flow was temporarily stopped using intravascular balloon. Postponed hemostasis was observed at lamb's femoral artery experiments for all HIFU treatments. It was demonstrated that HIFU can be used to stop active bleeding from vascular injuries including punctures and lacerations. The results of theoretical modeling, acoustic measurements, and in vivo vascular experiments prove the efficacy, safety and selectivity of developed HIFU transducers and methods used for enhancing of tissue lysis and hemostasis. [ABSTRACT FROM AUTHOR]

High Intensity Focused Ultrasound (HIFU) can be used for the localized heating of biological tissue through the conversion of sound waves into heat. Although originally developed for human medicine, HIFU may also be used to weaken the attachment of pin bones in fish fillets to enable easier removal of such bones. This was shown in the present study, where a series of experiments were performed on HIFU phantoms and fillets of cod and salmon. In thin objects such as fish fillets, the heat is mainly dissipated at the surfaces. However, bones inside the fillet absorb ultrasound energy more efficiently than the surrounding tissue, resulting in a “self-focusing” heating of the bones. Salmon skin was found to effectively block the ultrasound, resulting in a significantly lower heating effect in fillets with skin. Cod skin partly blocked the ultrasound, but only to a small degree, enabling HIFU treatment through the skin. The treatment of fillets to reduce the pin bone attachment yielded an average reduction in the required pulling force by 50% in cod fillets with skin, with little muscle denaturation, and 72% in skinned fillets, with significant muscle denaturation. Salmon fillets were treated from the muscle side of the fillet to circumvent the need for penetration through skin. The treatment resulted in a 30% reduction in the peak pulling force and 10% reduction in the total pulling work, with a slight denaturation of the fillet surface.

Purpose: To evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and PSA testing in follow-up after high intensity focused ultrasound (HIFU) focal therapy for localized prostate cancer.Methods: A total of 73 men with localized prostate cancer were prospectively enrolled and underwent focal HIFU followed by per-protocol PSA and mpMRI with systematic plus targeted biopsies at 12 months after treatment. We evaluated the association between post-treatment mpMRI and PSA with disease persistence on the post-ablation biopsy. We also assessed post-treatment functional and oncological outcomes.Results: Median age was 69 years (Interquartile Range (IQR): 66-74) and median PSA was 6.9 ng/dL (IQR: 5.3-9.9). Of 19 men with persistent GG ≥ 2 disease, 58% (11 men) had no visible lesions on MRI. In the 14 men with PIRADS 4 or 5 lesions, 7 (50%) had either no cancer or GG 1 cancer at biopsy. Men with false negative mpMRI findings had higher PSA density (0.16 vs. 0.07 ng/mL2, P = 0.01). No change occurred in the mean Sexual Health Inventory for Men (SHIM) survey scores (17.0 at baseline vs. 17.7 post-treatment, P = 0.75) or International Prostate Symptom Score (IPSS) (8.1 at baseline vs. 7.7 at 24 months, P = 0.81) after treatment.Conclusions: Persistent GG ≥ 2 cancer may occur after focal HIFU. mpMRI alone without confirmatory biopsy may be insufficient to rule out residual cancer, especially in patients with higher PSA density. Our study also validates previously published studies demonstrating preservation of urinary and sexual function after HIFU treatment. [ABSTRACT FROM AUTHOR]

Surgical extirpation of liver tumors remains a proven approach in the management of metastatic tumors to the liver, particularly those of colorectal origin. Ablative, non-resective therapies are an increasingly attractive primary therapy for liver tumors as they are generally better tolerated and result in far less morbidity and mortality. Ablative therapies preserve greater normal liver parenchyma allowing better post-treatment liver function and are particularly appropriate for treating subsequent liver-specific tumor recurrence. This article reviews the current status of ablative therapies for non-hepatocellular liver tumors with a discussion of many of the clinically available approaches.

Objectives: Our study aims at the comprehensive analysis of adverse events (AEs) in patients with symptomatic uterine fibroids (UFs) who underwent magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) in the last 6 years in one of the major Polish centers performing this type of therapy., Methods: The presented retrospective case-control study was conducted in the Department of Obstetrics and Gynecology, Pro-Familia Hospital, Rzeszów in cooperation with the Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, Warsaw. The study enrolled 372 women with symptomatic UFs who underwent MR-HIFU and reported AEs during or after the procedure. The occurrence of particular AEs was analyzed. Statistical comparison of two cohorts (patients with and without AEs) was conducted based on epidemiological factors, UF characteristics, fat layer thickness, the presence of abdominal scars and technical parameters of the procedure., Results: The overall mean occurrence rate of AEs was 8.9% ( n  = 33). No major AEs were reported. The only statistically significant risk factor of AEs was the treatment of type II UFs according to Funaki (OR 2.12, CI 95%, p  = 0.043). Other investigated factors did not have a statistically significant influence on AE occurrence. Abdominal pain was the most common AE., Conclusion: Our data showed that MR-HIFU seemed to be a safe procedure. The AE rate after the treatment is relatively low. According to the obtained data it seems that the occurrence of AEs does not depend on the technical parameters of the procedure and the volume, position and location of UFs. Further prospective, randomized studies and with long follow-up are necessary to confirm the final conclusions.

In transabdominal histotripsy, ultrasound pulses are focused on the body to noninvasively destroy soft tissues via cavitation. However, the ability to focus is limited by phase aberration, or decorrelation of the ultrasound pulses due to spatial variation in the speed of sound throughout heterogeneous tissue. Phase aberration shifts, broadens, and weakens the focus, thereby reducing the safety and efficacy of histotripsy therapy. This paper reviews and discusses aberration effects in histotripsy and in related therapeutic ultrasound techniques (e.g., high intensity focused ultrasound), with an emphasis on aberration by soft tissues. Methods for aberration correction are reviewed and can be classified into two groups: model-based methods, which use segmented images of the tissue as input to an acoustic propagation model to predict and compensate phase differences, and signal-based methods, which use a receive-capable therapy array to detect phase differences by sensing acoustic signals backpropagating from the focus. The relative advantages and disadvantages of both groups of methods are discussed. Importantly, model-based methods can correct focal shift, while signal-based methods can restore substantial focal pressure, suggesting that both methods should be combined in a 2-step approach. Aberration correction will be critical to improving histotripsy treatments and expanding the histotripsy treatment envelope to enable non-invasive, non-thermal histotripsy therapy for more patients.

Background: Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility., Case Presentation: A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (β-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up., Conclusion: Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility.

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F -number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications.

Purpose: Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons., Material and Methods: In vivo Achilles tendons ( n  = 28) from 15-20kg Yorkshire pigs ( n  = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed., Results: Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90 ° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16 ° to 27 ° . There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm 2 , 53.2mm 2 , 77.8mm 2 and 91.6mm 2 . The average areas of skin necrosis were 5.4mm 2 , 21.8mm 2 , 37.2mm 2 , and 91.4mm 2 . Histologic analysis confirmed tissue ablation and structural collagen fiber disruption., Conclusions: This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.

Breast cancer (BC) is the most frequently diagnosed malignancy among women. In the past two decades, new technologies and BC screening have led to the diagnosis of smaller and earlier-stage BC (ESBC). Therefore, percutaneous minimally invasive techniques (PMIT) were adopted to treat patients unfit for surgery, women who refuse it, or elderly patients with comorbidities that could make surgery a difficult and life-threatening treatment. The target of PMIT is small-size ESBC with the scope of obtaining similar efficacy as surgery. Minimally invasive treatments are convenient alternatives with promising effectiveness, lower morbidity, less cost, less scarring and pain, and more satisfying cosmetic results. Ablative techniques used in BC are cryoablation, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound (US), and laser ablation. The aim of our study is to discuss the current status of percutaneous management of BC, evaluate the clinical outcomes of PMIT in BC, and analyze future perspectives regarding ablation therapy in BC.

Objectives: This study intended to compare the safety and clinical efficacy between two treatments of uterine fibroids: laparoscopic myomectomy (LM) and high intensity focused ultrasound (HIFU)., Material and Methods: Clinical data were collected from 587 uterine fibroid patients who were treated in The People's Hospital of Nanchuan, Chongqing from January 1, 2018 to December 31, 2019. Among the patients, 287 cases were treated with HIFU (observation group), and 300 cases were treated with LM (control group). The progression-free survival (PFS) was taken as the primary endpoint. The secondary endpoints included operation results (including operative time, intraoperative blood loss, and intraoperative fluid replacement), complications, hemoglobin level one month after surgery and clinical efficacy. In addition, the fibroid volume of the observation group before treatment and 3, 6, and 12 months after treatment were also analyzed., Results: The operative time of observation group was evidently shortened compared to the control group, and the intraoperative blood loss and intraoperative fluid replacement of observation group were also considerably reduced (all p < 0.05), but there was no significant difference in the hemoglobin level between the two groups one month after surgery (p > 0.05). In terms of curative effect, the total effective rate of HIFU group and LM group was 98.6% (283/287) and 95.3% (286/300) respectively, with statistically significant difference (p < 0.05). In terms of complications, the incidence of bleeding and infection in HIFU group was obviously lower than that in LM group (both p < 0.05), while no significant differences were observed in the remaining complications (all p > 0.05). Fibroid volume comparisons before treatment and 3, 6 and 12 months after operation in observation group showed that fibroid volume decreased significantly (all p < 0.05). The median follow-up time was 30.6 months. The mean PFS of patients in the observation group and control group was 29.71 months (95% CI 28.24-29.75) and 26.74 months (95% CI 26.49-28.33), respectively (HR 0.47; 95% CI, 0.29 to 0.76; Log-rank p = 0.0019)., Conclusions: HIFU could improve the intraoperative efficacy and reduce the complications of patients with uterine fibroids and has excellent performance in improving clinical efficacy and prolonging PFS. HIFU can be used as an alternative to surgical treatment.

This study evaluates the feasibility of using high intensity focused ultrasound (HIFU) for the treatment of hydatid cysts of the liver. HIFU ablation was carried out in 62 patients with echinococcosis of the liver. The mean age of patients was 40.76 ± 14.84 (range: 17–72 years). The effectiveness of the treatment was monitored in real-time by changes in the gray-scale, and by morphological studies, computed tomography, magnetic resonance imaging, and ultrasound. Criteria for evaluating the effectiveness of treatment in real time were outlines. Cytomorphological picture of destructive changes of parasitic elements was presented as well. Loss of embryonic elements of the parasite was observed at the subcellular level after HIFU-ablation and underlines the effectiveness of HIFU. [ABSTRACT FROM AUTHOR]

Diffuse uterine leiomyomatosis (DUL) is a rare and unique type of uterine leiomyoma which affects women of reproductive age. While treatments like medication, uterine artery embolization (UAE) and hysteroscopic myomectomy show some effectiveness, hysterectomy is currently the only known treatment capable of eliminating the symptoms of this disease. This case report demonstrates that high intensity focused ultrasound (HIFU) ablation may offer these patients a new treatment strategy that could control the symptoms of DUL and spare the uterus from hysterectomy. [ABSTRACT FROM AUTHOR]

This study evaluates the feasibility of using high intensity focused ultrasound (HIFU) for the treatment of liver alveococcosis. HIFU ablation was carried out in 36 patients with alveococcosis of the liver. The median age of patients was 39.24 ± 12, 93 years (range: 20–66 years). The efficiency of treatment was monitored in real time with morphological evaluation, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and with morphological cytological and electron microscopy studies. HIFU ablation has shown effectiveness in destroying the protoscolexes, laminar and cell elements of the cuticular and germinal membrane of the alveococcosis larvocyst, causing the death of the cells of initial metamorphosis of alveococcosis, which is responsible for the dissemination of the parasite in the liver. Therefore HIFU-therapy is a promising and effective treatment for liver alveococcosis. [ABSTRACT FROM AUTHOR]

Evaluation of high intensity focused ultrasound (HIFU) treatment with MRI is generally based on assessment of the non-perfused volume from contrast-enhanced T1-weighted images. However, the vascular status of tissue surrounding the non-perfused volume has not been extensively investigated with MRI. In this study, cluster analysis of the transfer constant Ktrans and extravascular extracellular volume fraction ve, derived from dynamic contrast-enhanced MRI (DCE-MRI) data, was performed in tumor tissue surrounding the non-perfused volume to identify tumor subregions with distinct contrast agent uptake kinetics. DCE-MRI was performed in CT26.WT colon carcinoma-bearing BALB/c mice before ( n = 12), directly after ( n = 12) and 3 days after ( n = 6) partial tumor treatment with HIFU. In addition, a non-treated control group ( n = 6) was included. The non-perfused volume was identified based on the level of contrast enhancement. Quantitative comparison between non-perfused tumor fractions and non-viable tumor fractions derived from NADH-diaphorase histology showed a stronger agreement between these fractions 3 days after treatment ( R2 to line of identity = 0.91) compared with directly after treatment ( R2 = 0.74). Next, k-means clustering with four clusters was applied to Ktrans and ve parameter values of all significantly enhanced pixels. The fraction of pixels within two clusters, characterized by a low Ktrans and either a low or high ve, significantly increased after HIFU. Changes in composition of these clusters were considered to be HIFU induced. Qualitative H&E histology showed that HIFU-induced alterations in these clusters may be associated with hemorrhage and structural tissue disruption. Combined microvasculature and hypoxia staining suggested that these tissue changes may affect blood vessel functionality and thereby tumor oxygenation. In conclusion, it was demonstrated that, in addition to assessment of the non-perfused tumor volume, the presented methodology gives further insight into HIFU-induced effects on tumor vascular status. This method may aid in assessment of the consequences of vascular alterations for the fate of the tissue. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) is a non-invasive technique that allows a small, well-circumscribed thermal lesion to be generated within a tissue target. Tissue destruction occurs due to direct heating within the lesion and the mechanical effects of acoustic cavitation. HIFU has been used in a broad range of clinical applications, including the treatment of malignancies, uterine fibroids and cardiac arrhythmias. Interest in the use of the technique to treat pain has recently increased. A number of painful conditions have been successfully treated, including musculoskeletal degeneration, bone metastases and neuropathic pain. The exact mechanism by which HIFU results in analgesia remains poorly understood, but it is thought to be due to localised denervation of tissue targets and/or neuromodulatory effects. The majority of studies conducted investigating the use of HIFU in pain are still at an early stage, although initial results are encouraging. Further research is indicated to improve our understanding of the mechanisms underlying this treatment and to fully establish its efficacy; however, it is likely that HIFU will play a role in pain management in the future. This narrative review provides a synthesis of the recent, salient clinical and basic science research related to this topic and gives a general introduction to the mechanisms by which HIFU exerts its effects. [ABSTRACT FROM AUTHOR]

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T1, T2, ADC, amide proton transfer (APT), T1ρ and DCE-MRI measurements, to evaluate MR-guided HIFU treatment of subcutaneous tumors in rats. K-means clustering using all different combinations of the endogenous contrast MRI parameters (feature vectors) was performed to segment the multiparametric data into tissue populations with similar MR parameter values. The optimal feature vector for identification of the extent of non-viable tumor tissue after HIFU treatment was determined by quantitative comparison between clustering-derived and histology-derived non-viable tumor fractions. The highest one-to-one correspondence between these clustering-based and histology-based non-viable tumor fractions was observed for the feature vector {ADC, APT-weighted signal} ( R2 to line of identity ( R2 y= x) = 0.92) and the strongest agreement was seen 3 days after HIFU ( R2y=x = 0.97). To compare the multiparametric MRI analysis results with conventional HIFU monitoring and evaluation methods, the histology-derived non-viable tumor fractions were also quantitatively compared with non-perfused tumor fractions (derived from the level of contrast enhancement in the DCE-MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240 cumulative equivalent minutes at 43 °C). The correlation between histology-derived non-viable tumor fractions directly after HIFU and the 240 CEM fractions was high, but not significant. The non-perfused fractions overestimated the extent of non-viable tumor tissue directly after HIFU, whereas an underestimation was observed 3 days after HIFU. In conclusion, we have shown that a multiparametric MR analysis, especially based on the ADC and the APT-weighted signal, can potentially be used to determine the extent of non-viable tumor tissue 3 days after HIFU treatment. We expect that this method can be incorporated in the current clinical workflow of MR-HIFU ablation therapies. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Electromagnetic compatibility (EMC) is a key issue in the design and development of safe and effective medical instruments. The treatment probes of high intensity focused ultrasound (HIFU) systems not only receive and transmit electromagnetic waves, but also radiate ultrasound waves, resulting in electromagnetic coupling. In this paper, an electromagnetic shielding method involving the enclosure of the probe in a copper wire mesh was introduced. First, sound pressure distribution simulations and measurements were performed using a hydrophone in order to evaluate the effects of the wire mesh on the acoustic performance of the HIFU system. The results indicated that the wire mesh did not disturb the normalized sound pressure field. In addition, the attenuation of the maximum pressure in the focal plane was equal to 6.2%. Then, the electronic emission level was tested in a chamber. After the implementation of the wire mesh, the 10-100 MHz frequency band radiation was suppressed, and the HIFU system satisfied the national EMC standards. [ABSTRACT FROM AUTHOR]

Purpose: The pleiotropic effects of heat on cancer cells have been well documented. The biological effects seen depend on the temperature applied, and the heating duration. In this study we investigate the cytotoxic effects of heat on colon cancer cells and determine how different cell death processes such as autophagy, apoptosis and necroptosis play a role in cell response. Materials and methods: The thermal dose concept was used to provide a parameter that will allow comparison of different thermal treatments. Two human colon cancer cell lines, HCT116 and HT29, were subjected to ablative temperatures using a polymerase chain reaction thermal cycler. Temperature was recorded using thermocouples. Cell viability was assessed using the MTT assay. Induction of apoptosis was estimated using an enzyme-linked immunosorbent assay that detects cleaved cytoplasmic nucleosomes. Protein regulation was determined using immunoblotting. The percentage of cells undergoing apoptosis and autophagy was determined with annexin V/propidium iodide staining and a cationic amphiphilic tracer using fluorescence-activated cell sorting analysis. Results: Exposure of colon cancer cells to ablative thermal doses results in decreased cell viability. The cytotoxic effect of heat is associated with induction of apoptosis and autophagy, the amount depending on both the thermal dose applied and on the time elapsed after treatment. Autophagy induction is mainly seen in live cells. RIPK3 protein levels are increased after exposure of cells to heat. A necroptosis inhibitor does not affect cell viability. Conclusions: Autophagy, apoptosis and necroptosis are associated with the response of these cancer cell lines to supra-normal temperatures. [ABSTRACT FROM AUTHOR]

This study presents a new approach for evaluating bioheat transfer equation (BHTE) models used in treatment planning, control and evaluation of all thermal therapies. First, 3D magnetic resonance temperature imaging (MRTI) data are used to quantify blood flow-related energy losses, including the effects of perfusion and convection. Second, this information is used to calculate parameters of a BHTE model: in this paper the widely used Pennes BHTE. As a self-consistency check, the BHTE parameters are utilized to predict the temperatures from which they were initially derived. The approach is evaluated with finite-difference simulations and implemented experimentally with focused ultrasound heating of an ex vivo porcine kidney perfused at 0, 20 and 40 ml/min ( n = 4 each). The simulation results demonstrate accurate quantification of blood flow-related energy losses, except in regions of sharp blood flow discontinuities, where the transitions are spatially smoothed. The smoothed transitions propagate into estimates of the Pennes perfusion parameter but have limited effect on the accuracy of temperature predictions using these estimates. Longer acquisition time periods mitigate the effects of MRTI noise, but worsen the effect of flow discontinuities. For the no-flow kidney experiments the estimates of a uniform, constant Pennes perfusion parameter are approximately zero, and at 20 and 40 ml/min the average estimates increase with flow rate to 3.0 and 4.2 kg/m3/s, respectively. When Pennes perfusion parameter values are allowed to vary spatially, but remain temporally constant, BHTE temperature predictions are more accurate than when using spatially uniform, constant Pennes perfusion values, with reductions in RMSE values of up to 79%. Locations with large estimated perfusion values correspond to high flow regions of the kidney observed in T1-weighted MR images. This novel, MRTI-based technique holds promise for improving understanding of thermal therapy biophysics and for evaluating biothermal models. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Advances in transcranial MRI-guided focused ultrasound have renewed interest in lesioning procedures in functional neurosurgery with a potential role in the treatment of neurological conditions such as chronic pain, brain tumours, movement disorders and psychiatric diseases. While the use of transcranial MRI-guided focused ultrasound represents a new innovation in neurosurgery, ultrasound has been used in neurosurgery for almost 60 years. This paper reviews the major historical milestones that have led to modern transcranial focused ultrasound and discusses current and evolving applications of ultrasound in the brain. [ABSTRACT FROM AUTHOR]

Purpose: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. Methods: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. Results: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastastic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. Conclusions: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours. [ABSTRACT FROM AUTHOR]

Purpose This study was aimed to assess the effects of High Intensity Focused Ultrasound (HIFU) thermal ablation on tumor T1ρ. Methods In vivo T1ρ measurements of murine tumors at various spin-lock amplitudes ( B1 = 0-2000 Hz) were performed before ( n = 13), directly after ( n = 13) and 3 days ( n = 7) after HIFU treatment. T2 maps were obtained from the measurements at B1 = 0 Hz. Results Average tumor T1ρ distributions at the different experimental time points showed a shift toward lower T1ρ values after HIFU for all spin-lock amplitudes, which became larger with increasing spin-lock amplitude at 3 days after treatment. Statistical analysis confirmed a significant effect of spin-lock amplitude on the average change in T1ρ (ΔT1ρ) as compared to baseline at 3 days after HIFU. At 3 days after treatment, ΔT1ρ values at B1 above 100 Hz were significantly lower (more negative) than at B1 = 0 Hz (T2). Conclusion Significant changes in tumor T1ρ were observed after HIFU treatment. These T1ρ changes were distinctly more pronounced than HIFU-induced changes in T2. The results indicate that T1ρ imaging is sensitive to HIFU-induced tissue changes and may thus be a suitable MR method for the evaluation of HIFU treatment. Magn Reson Med 73:1593-1601, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

There is a need for a coherent set of exposure and dose quantities to describe ultrasound fields in media other than water (including tissue and tissue-simulating materials). This paper proposes an outline dosimetry scheme, with quantities for free field exposure, in situ exposure, dose (both instantaneous and cumulative) and effect, to act as a structure for organising a more complete set of definitions. It also presents findings from a survey of the views of the therapeutic ultrasound community which generally supports the principle of using modified free field quantities to describe the in situ field, and the prioritising of dose quantities which are related to heating and thermal mechanisms. Although there is no one-to-one relationship between any known ultrasound dose quantity and a specific biological effect, this can also be said of radiotherapy and other modalities where weighting factors have been developed to calculate the degree of equivalence between different tissues and radiation types. This same separation is recommended for ultrasound, provided that an appropriate set of recognised 'engineering' quantities can be established for exposure and dose quantities. [ABSTRACT FROM AUTHOR]

This paper reviews ultrasound imaging methods for the guidance of therapeutic focused ultrasound (USgFUS), with emphasis on real-time preclinical methods. Guidance is interpreted in the broadest sense to include pretreatment planning, siting of the FUS focus, real-time monitoring of FUS-tissue interactions, and real-time control of exposure and damage assessment. The paper begins with an overview and brief historical background of the early methods used for monitoring FUS-tissue interactions. Current imaging methods are described, and discussed in terms of sensitivity and specificity of the localisation of the FUS effects in both therapeutic and sub-therapeutic modes. Thermal and non-thermal effects are considered. These include cavitation-enhanced heating, tissue water boiling and cavitation. Where appropriate, USgFUS methods are compared with similar methods implemented using other guidance modalities, e.g. magnetic resonance imaging. Conclusions are drawn regarding the clinical potential of the various guidance methods, and the feasibility and current status of real-time implementation. [ABSTRACT FROM AUTHOR]

As the use of HIFU in the clinic becomes more widespread there is an ever increasing need to standardise quality assurance protocols, an important step in facilitating the wider acceptance of HIFU as a therapeutic modality. This article reviews pertinent aspects of HIFU treatment delivery, encompassing the closely related aspects of quality assurance and calibration. Particular attention is given to the description and characterisation of relevant acoustic field parameters and the measurement of acoustic power. Where appropriate, recommendations are made. [ABSTRACT FROM AUTHOR]

In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour ( n = 6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD. [ABSTRACT FROM AUTHOR]

Introduction Iatrogenic atrial tachyarrhythmias have increased with the widespread application of left atrial ablative procedures to treat atrial fibrillation. Methods and results Entrainment and activation mapping were utilized to study the mechanisms of atrial flutter in two patients who presented with atypical atrial flutter after high intensity focused ultrasound (HIFU) atrial ablation for persistent atrial fibrillation during the course of concomitant cardiac surgery. Case 1: Atrial flutter with CL of 340 ms was demonstrated to be mediated by entry into and exit from the partially isolated posterior left atrium (LA) with conduction delay across at least one of the connections. The exit site was near the left superior pulmonary vein (LSPV) and the entrance site was near the right inferior pulmonary vein (RIPV) as demonstrated by activation and entrainment mapping. Case 2: Entrainment mapping was highly suggestive of inferior exit from the HIFU ablation line between the two inferior pulmonary veins. Flutter terminated during trans-septal procedure and could not be re-induced. Activation mapping of the LA during pacing revealed the inferior exit and left superior entrance site, both of which were successfully ablated, isolating the posterior LA. Conclusions Re-entrant atrial flutter post-HIFU epicor Maze is caused by slow conduction at entry and exit sites from the otherwise isolated posterior LA wall. In both cases, gaps were found close to the LSPV and RIPV which may reflect difficulty in achieving proper contact between the HIFU device and the left atrial wall at these sites. These gaps are amenable to catheter ablation. [ABSTRACT FROM AUTHOR]

Background: The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility., Case Presentation: A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up., Conclusion: Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding., (© 2022. The Author(s).)

Background: No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication., Methods: We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated., Results: A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm 3 , p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time ( p = 0.001), treatment duration ( p = 0.002), and ablated energy ( p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm 3 /min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency ( p = 0.067), treatment speed ( p = 0.007), treatment efficiency ( p = 0.001), NPV per energy ( p = 0.005), and NPV per sonication ( p = 0.004) than other 2 groups., Conclusion: Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Hsu, Huang, Cheng, Chang and Chou.)