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High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions.

The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0–87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

The biological focal region (BFR) induced by a single high-intensity focused ultrasound (HIFU) exposure is considered to be the foundation of the ultrasound ablation of tumor lesions. The purpose of this study was to explore the relationship between the acoustic focal region (AFR) and the BFRs with different combinations of power and time in low-power cumulative HIFU treatment. The finite-difference time-domain (FDTD) method was used to simulate AFR and BFR during HIFU ablation. The acoustic fields, the temperature profiles, and the shapes of BFRs were calculated by the Westervelt equation, Pennes’ equation, and the equivalent thermal dose model. In order to verify the simulation rules, phantom and ex vivo bovine livers were exposed by HIFU with a different power and time. The results demonstrated that in the low-power cumulative HIFU treatment, when the lengths of BFRs and the length of AFR were approximately equal, the shape of the BFR induced by ‘high power × short time’ exposure was closer to that of AFR than the shape of the BFR induced by ‘low power × long time’ exposure, and the exposure energy required was significantly reduced. The analysis revealed the relationship between the BFR and the AFR with different acoustic power. This study provides a reference for doctors to determine power, time, and movement distance in clinical treatment.

According to the traditional method of high intensity focused ultrasound (HIFU) treatment, the acoustic and thermal characteristic parameters of constant temperature (room temperature or body temperature) are used to predict thermal lesion. Based on the nonlinear spherical beam equation (SBE) and Pennes bio-heat transfer equation, and a new acoustic-thermal coupled model is proposed. The constant and temperature-dependent acoustic and thermal characteristic parameters are used to predict thermal lesion, and the predicted lesion area are compared with each other. Moreover, the relationship between harmonic amplitude ratio (P2/P1) and thermal lesion is studied. Combined with the known experimental data of acoustic and thermal characteristic parameters of biological tissue and data fitting method, the relationship between acoustic and thermal characteristic parameters and temperature is obtained; and the thermal lesion simulation calculation is carried out by using the acoustic and thermal characteristic parameters under constant temperature and temperature- dependent acoustic and thermal characteristic parameters, respectively. The simulation results show that under the same irradiation condition, the thermal lesion predicted by temperature-dependent acoustic and thermal characteristic parameters is larger than that predicted by traditional method, and the thermal lesion increases with the decrease of harmonic amplitude ratio.

Objective To investigate the prevalence of pelvic adhesions in patients with uterine fibroids after high-intensity focused ultrasound (HIFU) treatment, then analyze the influencing factors of pelvic adhesions. Materials and methods From October 2010 to March 2020, a total of 2619 patients with uterine fibroids underwent either hysterectomy, myomectomy, or cesarean section in Suining Central Hospital of Sichuan province. Of the 2619 patients, 810 were excluded because of a documented history of either pelvic infections, endometriosis, prior abdominopelvic surgery, or gynecological malignancies; 1809 patients were enrolled and the data were retrospectively assessed for the prevalence and patterns of pelvic adhesions. Among them, 96 patients with uterine fibroids had had prior HIFU treatment (HIFU group), 1713 patients had not had HIFU or surgical treatments (control group). Results Among the 96 patients in the HIFU group, adhesions were detected in 42 patients, the incidence of pelvic adhesion being 43.75%; the 1713 patients in the control group, adhesions were detected in 619 patients, the prevalence of pelvic adhesion being 36.14%. No statistically significant difference in the incidence of adhesion between the two groups was observed (p = .132), no significant difference in location of pelvic adhesions between the two groups and no significant difference in the severity of adhesions between the two groups was observed (p > .05). Conclusions Based on our results with limited numbers, we concluded that HIFU treatment did not significantly increase the risk of pelvic adhesions.

Background Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a ‘best-guess’ treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging. Methods The algorithm was developed from volunteer images and tested with patient data. MR images were acquired for five healthy volunteers and five patients with recurrent gynaecological cancer. Subjects were MR imaged supine and in oblique-supine-decubitus MRgHIFU treatment positions. Body outline and bones were segmented for all subjects, with organs-at-risk and tumors also segmented for patients. Supine images were aligned with treatment images to simulate a treatment dataset. Target coverage (of patient tumors and volunteer intra-pelvic soft tissue), i.e. the volume reachable by the MRgHIFU focus, was quantified. Target coverage predicted from supine imaging was compared to that from treatment imaging. Results Mean (±standard deviation) absolute difference between supine-predicted and treatment-predicted coverage for 5 volunteers was 9 ± 6% (range: 2–22%) and for 4 patients, was 12 ± 7% (range: 4–21%), excluding a patient with poor acoustic coupling (coverage difference was 53%). Conclusion Prediction of MRgHIFU target coverage from referral imaging appears feasible, facilitating further development of automated evaluation of patient suitability for MRgHIFU.

Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect.Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (in vivo via MR thermometry. Histological data was collected for lesion assessment.Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters.Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment.

We report on a patient who underwent magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy to treat tremor 3 years after a stereotactic radiosurgery (SRS) thalamotomy. The SRS produced only limited and transient improvements and was associated with a persistent hyperintensity on T2-FLAIR MR images. The MRgFUS thalamotomy was successful, with tremor improvement at 3 months, no adverse effects, and radiological appearance of the MRgFUS lesion similar to other patients undergoing this therapy. We also observed that the SRS-related T2-FLAIR hyperintensity had increased signal intensity 1 day post-MRgFUS, but appeared completely resolved 3 months post-MRgFUS. In conclusion, the case demonstrates that MRgFUS thalamotomy may effectively control tremor in patients with a history of SRS thalamotomy. We also speculate on the potential mechanisms of the apparent resolution of radiation-related change, and discuss possible applications of MRgFUS to reduce persistent SRS-related inflammation. Keywords: Magnetic resonance guided focused ultrasound, High intensity focused ultrasound, Radiation, Thalamotomy, Tremor

Conventional tissue engineering approaches rely on scaffold-based delivery of exogenous proteins, genes, and/or cells to stimulate regeneration via growth factor signaling. However, scaffold-based approaches do not allow active control of dose, timing, or spatial localization of a delivered growth factor once the scaffold is implanted, yet these are all crucial parameters in promoting tissue regeneration. To address this limitation, we developed a stable cell line containing a heat-activated and rapamycin-dependent gene expression system. In this study, we investigate how high intensity focused ultrasound (HIFU) can spatiotemporally control firefly luciferase (fLuc) transgene activity both in vitro and in vivo by the tightly controlled generation of hyperthermia. Cells were incorporated into composite scaffolds containing fibrin and hydroxyapatite particles, which yielded significant increases in acoustic attenuation and heating in response to HIFU compared to fibrin alone. Using 2.5 MHz HIFU, transgene activation was observed at acoustic intensities of 201 W/cm2 and higher. Transgene activation was spatially patterned in the scaffolds by rastering HIFU at speeds up to 0.15 mm/s. In an in vivo study, a 67-fold increase in fLuc activity was observed in scaffolds exposed to HIFU and rapamycin versus rapamycin only at 2 days post implantation. Repeated activation of transgene expression was also demonstrated 8 days after implantation. No differences in in vivo scaffold degradation or compaction were observed between +HIFU and -HIFU groups. These results highlight the potential utility of using this heat-activated and rapamycin-dependent gene expression system in combination with HIFU for the controlled stimulation of tissue regeneration.

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life.

Objectives Fiducial markers improve accuracy in external beam radiation therapy (EBRT) for treatment of prostate cancer (PCa). However, many patients recur after EBRT necessitating additional treatment, such as MR-guided transurethral ultrasound ablation (TULSA). Residual markers may compromise TULSA through ultrasound field distortions and generation of local susceptibility artifacts. The objective was to investigate how markers affect the ablation outcome during clinical TULSA treatments. Subjects and methods A retrospective analysis was performed on nine patients with radiorecurrent PCa and residual markers who received TULSA. The MR susceptibility artifact was quantified as a function of marker type, size and orientation, in particular for thermometry. The spatial distribution of markers inside the prostate was recorded, and the resulting impact on the thermal dose was measured. The thermal dose measurements were directly compared to the residual enhancing prostatic tissue observed on the immediate and control post-TULSA contrast enhanced (CE) image. Results Successful thermal dose accumulation to the target boundary occurred for 14/20 (70%) of markers, confirmed with CE imaging. Gold markers situated simultaneously close to the urethra (≤12 mm) and far from the target boundary (≥13 mm) reduced the ultrasound depth of heating. Nitinol markers produced large, hypointense artifacts that disrupted thermometry and compromised treatment. Artifacts from gold markers were less pronounced, but when located near the target boundary, also affected treatment. Conclusion Marker composition, orientation and location inside the prostate can all potentially impact treatment outcome. Proper patient selection through detailed MRI screening is critical to ensure successful radiorecurrent PCa treatment outcomes with TULSA.

Smart materials are intelligent materials that change their structural, chemical, mechanical, or thermal properties in response to an external stimulus such as heat, light, and magnetic and electric fields. With the increase in usage of smart materials in many sensitive applications, the need for a remote, wireless, efficient, and biologically safe stimulus has become crucial. This dissertation addresses this requirement by using high intensity focused ultrasound (HIFU) as the external trigger. HIFU has a unique capability of maintaining both spatial and temporal control and propagating over long distances with reduced losses, to achieve the desired response of the smart material. Two categories of smart materials are investigated in this research; shape memory polymers (SMPs) and piezoelectric materials. SMPs have the ability to store a temporary shape and returning to their permanent or original shape when subjected to an external trigger. On the other hand, piezoelectric materials have the ability to convert mechanical energy to electrical energy and vice versa. Due to these extraordinary properties, these materials are being used in several industries including biomedical, robotic, noise-control, and aerospace. This work introduces two novel concepts: First, HIFU actuation of SMP-based drug delivery capsules as an alternative way of achieving controlled drug delivery. This concept exploits the pre-determined shape changing capabilities of SMPs under localized HIFU exposure to achieve the desired drug delivery rate. Second, solving the existing challenge of low efficiency by focusing the acoustic energy on piezoelectric receivers to transfer power wirelessly. The fundamental physics underlying these two concepts is explored by developing comprehensive mathematical models that provide an in-depth analysis of individual parameters affecting the HIFU-smart material systems, for the first time in literature. Many physical factors such as acoustic, material and dynamical nonlinearities, acoustic standing waves, and mechanical behavior of materials are explored to increase the developed models' accuracy. These mathematical frameworks are designed with the aim of serving as a basic groundwork for building more complex smart material-based systems under HIFU exposure. Doctor of Philosophy Smart materials are a type of intelligent materials that have the ability to respond to external stimuli such as heat, light, and magnetic fields. When these materials respond, they can change their structural, thermodynamical, mechanical or chemical nature. Due to this extraordinary property, smart materials are being used in many applications including biomedical, robotic, space, microelectronics, and automobile industry. However, due to increased sensitivity and need for safety in many applications, a biologically safe, wireless, and efficient trigger is required to actuate these materials. In this dissertation, sound is used as an external trigger to actuate two types of smart materials: shape memory polymers (SMPs) and piezoelectric materials. SMPs have an ability to store a temporary (arbitrarily deformed) shape and return to their permanent shape when exposed to a trigger. In this dissertation, focused sound induced thermal energy acts as a trigger for these polymers. A novel concept of focused ultrasound actuation of SMP-based drug delivery capsules is proposed as a means to solve some of the challenges being faced in the field of controlled drug delivery. Piezoelectric materials have an ability to generate electric power when an external mechanical force is applied and vice versa. In this study, sound pressure waves supply the external force required to produce electric current in piezoelectric disks, as a method for achieving power transfer wirelessly. This study aims to solve the current problem of low efficiency in acoustic power transfer systems by focusing sound waves. This dissertation addresses the fundamental physics of high intensity focused ultrasound actuation of smart materials by developing comprehensive mathematical models and systematic experimental investigations, that have not been performed till now. The developed models enable an in-depth analysis of individual parameters including nonlinear material behavior, acoustic nonlinearity and resonance phenomena that affect the functioning of these smart systems. These mathematical frameworks also serve as groundwork for developing more complex systems.

Mesenchymal stromal cell (MSC) therapies combined with renal pulsed focused ultrasound (pFUS) pretreatment increase MSC homing and improve cisplatin‐induced acute kidney injury (AKI) better than MSC alone. However, mechanisms underlying improved outcomes remain unknown. We hypothesize pFUS up‐regulates renal interferon‐γ (IFNγ) and stimulates MSC to produce interleukin‐10 (IL‐10) after migrating to kidneys. To demonstrate initially, MSC cultured with IFNγ up‐regulated IL‐10. More MSC‐derived IL‐10 was detected in kidneys when IFNγ‐stimulated MSC were infused and they improved AKI better than unstimulated MSC. Next, IFNγ‐knockout mice with AKI received pFUS+MSC, but MSC‐derived IL‐10 expression and AKI were similar to using MSC alone. AKI in wild‐type mice receiving pFUS and IL‐10‐deficient MSC was also unimproved compared to administering IL‐10‐deficient MSC alone. Indoleamine 2,3‐dioxygenase (IDO), an anti‐inflammatory enzyme up‐regulated in MSC by IFNγ, was up‐regulated during AKI, but was not further elevated in MSC from pFUS‐treated kidneys, suggesting that IDO is not involved in improved AKI healing by pFUS+MSC. These data suggest IFNγ is up‐regulated by pFUS and after i.v.‐infused MSC home to pFUS‐treated kidneys, IFNγ stimulates additional IL‐10 production by MSC to improve AKI. Analogous mechanisms of ultrasound‐treated tissue microenvironments stimulating therapeutic MSC may exist in other pathologies where adjuvant ultrasound techniques are successful.

High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24 h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.

International audience; Transcranial brain therapy has recently emerged as a non-invasive strategy for the treatment of various neurological diseases, such as essential tremor or neurogenic pain. However, treatments require millimetre-scale accuracy. The use of high frequencies (typically ≥1 MHz) decreases the ultrasonic wavelength to the millimetre scale, thereby increasing the clinical accuracy and lowering the probability of cavitation, which improves the safety of the technique compared with the use of low-frequency devices that operate at 220 kHz. Nevertheless, the skull produces greater distortions of high-frequency waves relative to low-frequency waves. High-frequency waves require high-performance adaptive focusing techniques, based on modelling the wave propagation through the skull. This study sought to optimise the acoustical modelling of the skull based on computed tomography (CT) for a 1 MHz clinical brain therapy system. The best model tested in this article corresponded to a maximum speed of sound of 4000 m.s-1 in the skull bone, and it restored 86% of the optimal pressure amplitude on average in a collection of six human skulls. Compared with uncorrected focusing, the optimised non-invasive correction led to an average increase of 99% in the maximum pressure amplitude around the target and an average decrease of 48% in the distance between the peak pressure and the selected target. The attenuation through the skulls was also assessed within the bandwidth of the transducers, and it was found to vary in the range of 10 ± 3 dB at 800 kHz and 16 ± 3 dB at 1.3 MHz.

Managing patient expectations can be a difficult task and is one that cosmetic dermatologists frequently encounter. Misinformation and unrealistic expectations can oftentimes exist regarding cosmetic procedures and their results. These misconceptions can result in patient dissatisfaction and frustration on the physician's behalf. This case report underscores the importance of utilizing what is arguably the most basic and ancient tool in the office, the mirror. There are many different facets to the patient encounter and a variety of devices at the physician's disposal. Proper use of this valuable tool can improve communication, elucidate patient concerns, and reflect the focus on the patient. These can ultimately lead to improved procedure outcome and patient satisfaction. © 2018 Wiley Periodicals, Inc.

Acoustic cavitation which occurs at high intensities of ultrasound waves can be fatal for tumor cells. The existence of dissolved gases and also the presence of nanoparticles (NPs) in a liquid, irradiated by ultrasound, decrease the acoustic cavitation onset threshold and the resulting bubbles collapse. On the other hand, due to unique capabilities and optical properties of gold nanoparticles (GNPs), they have been emphasized as effective NPs in the field of tumor therapy. Absorption of the laser light by GNPs causes the water molecules around the NPs to evaporate and produces vapor cavities. In this paper, we have reviewed published studies in the fields of ultrasound therapy, sonodynamic therapy (SDT) and synergism of low-level ultrasound and also laser radiation in the presence of GNPs.

Purpose: Osteomyelitis is one of the most serious complications linked to diabetes and increases the possibility of limb amputation considerably. There exists an important clinical need to improve management of osteomyelitis, especially for diabetic patients who are more susceptible to failures, relapses and chronicity of multiple bone infections. Magnetic resonance-guided focused ultrasound (MRgFUS) can offer a clinical management option for patients with osteomyelitis by providing a non-surgical and potentially rapid-recovery treatment option. Material and Methods: A retrospective study with patients with confirmed osteomyelitis (n = 75) was performed at evaluating the feasibility to target bone infection sites with a clinically approved MRgFUS device (Sonalleve, Profound Medical, Mississauga, ON, Canada). The developed methodology allows using preexisting diagnostic magnetic resonance imaging (MRI) or computed tomography (CT) scans to evaluate the treatment feasibility directly using a MRgFUS treatment planning software. Results: 74.7% of the cases included in our study passed the targetability criteria. Cases were deemed non-targetable if the target was less than 1 cm from the skin or close to a neuro-vascular bundle, metallic implants, or in the way of a defect in the overlying skin. For cases that passed the targetability criteria, an average among patients of 92.7 ± 5.2% of the gross treatment volume could be reached using treatment cells available at the Sonalleve system. Conclusion: The retrospective study presented here is the first step to demonstrate the feasibility of utilizing MRgFUS for the thermal treatment of osteomyelitis.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF

Shuang-fen Tao, Wen-hua Gu, Jian-chun Gu, Mei-ling Zhu, Qing Wang, Lei-zhen Zheng Oncology Department, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People’s Republic of ChinaCorrespondence: Lei-zhen ZhengOncology Department, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People’s Republic of ChinaEmail zhengleizhen@xinhuamed.com.cnPurpose: This retrospective study was conducted to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with Gemcitabine and Oxaliplatin (Gemox) for the treatment of middle and advanced pancreatic cancer in elderly patients.Methods: Forty-seven patients with pancreatic cancer treated with HIFU and Gemox were evaluated for inclusion, and 38 cases were finally included. The primary endpoint was safety. Secondary endpoints included the response rate, the clinical benefit response (CBR), overall survival (OS), progression-free survival (PFS).Results: After combination therapy of HIFU and Gemox, severe complications were rarely reported, and no treatment-related death occurred. The rate of three or four-degree myelosuppression was low, and no obvious impairment of hepatorenal function was observed. Pancreatitis and gastrointestinal injury did not occurred. The disease control rate (DCR) was estimated to be 76.3%, including complete remission (CR), partial remission (PR), stable disease (SD) in 1, 6, 22 cases, respectively. And the objective response rate (ORR) was 18.4%. The clinical benefit rate (CBR) was 68.4%, with the pain significantly relieved (P

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel non-invasive ablation technique that uses focused sound energy to destroy focal tumors, primarily via heat deposition. It is widely used for palliation of pain from bone metastases and has also recently gained popularity as a technique for ablation of benign bone tumors and facet degenerative joint disease (rhizotomy). Clinically, in a subset of patients who have undergone MRgFUS of bone, a variety of treatment responses have been noted on follow-up imaging, including focal sclerosis within the target lesion or more exuberant proliferative changes associated with the periosteum. In this study, high resolution peripheral quantitative CT (HR-pQCT) was used to evaluate remodeling of bone following ablation in a swine model of MRgFUS and compared to samples from a control, non-treated femur. Within each treated femur, two lesions were created: a higher energy focused ultrasound dose was used for one lesion compared to a lower energy dose for the second lesion. Exuberant, extra-cortical bone formation was detected at the higher energy ablation zones, with volumes ranging from 340 mm3 to 1040 mm3. More subtle endosteal and cortical changes were detected in the lower energy ablation zones, however cortical thickness was significantly increased at these sites compared to control bone. For both high and low energy lesions, lower bone mineral density and tissue mineral density was noted in treated regions compared to control regions, consistent with the formation of newly mineralized tissue. Following HR-pQCT analysis, Fourier transform infrared (FTIR) spectroscopy was subsequently used to detect biochemical changes associated with remodeling of bone following MRgFUS, and compared to samples from the control, non-treated femur. Findings were compared with histopathologic examination following hematoxylin-eosin staining. FTIR analysis demonstrated lower mineral/phosphate ratio and increased crystallinity compared to the control samples (p = 0.013). Histopathologic review demonstrated associated areas of endosteal inflammation, scarring, fat necrosis, and new extra-cortical bone formation associated with the ablations. Overall, these findings provide novel characterization of new bone formation following MRgFUS ablation.

Effect of high intensity focused ultrasound (HIFU) uterine fibroid ablation on the endometrial receptivity and sex hormone level in uterine fibroid patients and the influencing factors for treatment rate were investigated. A retrospective analysis of 266 uterine fibroid patients admitted to the Department of Gynaecology in the Jining Maternity and Child Care Hospital from October 2013 to October 2016 was performed. Among them, observation group was treated with HIFU ablation (n=143), control group with myomectomy (n=123). The pulsatility index (PI) and the resistance index (RI) of the uterine arterial blood flow were measured during the luteal phase of menstruation by transvaginal ultrasonography. The serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were detected by chemical immunofluorescence. The relationship between HIFU treatment rate and clinical pathology of uterine fibroid patients was analyzed, and univariate/multivariate regression analysis was used to analyze the influencing factors for HIFU treatment rate. There was no significant difference in preoperative and postoperative PI and RI between the two groups (P>0.05); no significant difference between preoperative and postoperative PI/RI in the same group (P>0.05). There was no significant difference in preoperative and postoperative LH, FSH and E2 between the two groups (P>0.05); no significant difference between preoperative LH and postoperative LH in the same group (P>0.05), neither FSH or E2 (P>0.05). Results of multivariate analysis showed that fibroid location and ultrasound contrast intensity were independent influencing factors for HIFU treatment rate (P

Highlights • 2D nonlinear wave propagation with a bubble at the HIFU focus is simulated. • Constructive interference of a backscattered wave with incoming shockwaves appears. • Shock scattering effect is the mechanism for the formation of a cavitation cloud., Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble. The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. A numerical simulation of 2D nonlinear wave propagation with the presence of a bubble at the focus of a HIFU field was performed using the k-Wave MATLAB toolbox for time domain ultrasound simulations, which numerically solves the generalised Westervelt equation. The numerical results clearly demonstrate the appearance of the constructive interference of a backscattered shockwave by a bubble with incoming incident shockwaves. This interaction (i.e., the reflected and inverted peak positive phase from the bubble with the incoming incident rarefactional phase) can eventually induce a greater peak negative pressure field compared to that without the bubble at the HIFU focus. In addition, the backscattered peak negative pressure magnitude gradually increased from 17.4 MPa to 31.6 MPa when increasing the bubble size from 0.2 mm to 1.5 mm. The latter value is above the intrinsic cavitation threshold of –28 MPa in soft tissue. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.

In this study, plasmonic gold nanoparticles were simultaneously exposed to pulsed near-infrared laser light and high intensity focused ultrasound (HIFU) for the controllable nucleation of cavitation in tissue-mimicking gel phantoms. This in vitro protocol was developed to demonstrate the feasibility of this approach, for both enhancement of imaging and therapeutic applications for cancer. The same apparatus can be used for both imaging and therapeutic applications by varying the exposure duration of the HIFU system. For short duration exposures (10 µs), broadband acoustic emissions were generated through the controlled nucleation of inertial cavitation around the gold nanoparticles. These emissions provide direct localization of nanoparticles. For future applications, these particles may be functionalized with molecular-targeting antibodies (e.g. anti-HER2 for breast cancer) and can provide precise localization of cancerous regions, complementing routine diagnostic ultrasound imaging. For continuous wave (CW) exposures, the cavitation activity was used to increase the localized heating from the HIFU exposures resulting in larger thermal damage in the gel phantoms. The acoustic emissions generated from inertial cavitation activity during these CW exposures was monitored using a passive cavitation detection (PCD) system to provide feedback of cavitation activity. Increased localized heating was only achieved through the unique combination of nanoparticles, laser light and HIFU. Further validation of this technique in pre-clinical models of cancer is necessary.

PURPOSE We compared the effectiveness of high intensity focused ultrasound (HIFU) and radioiodine (RAI) to treat patients carrying toxic thyroid nodule (TTN). Normalization of serum thyrotropin (TSH) 1 year after treatment was the primary end-point; concurrent changes in nodules' volume and scintigraphic pattern were also evaluated as secondary end-points. MATERIALS AND METHODS Among patients ≥18 years old with TTN observed at our centre between January 1st, 2016 and December 31th, 2016 we prospectively enrolled 17 and 15 age and sex-matched patients treated with RAI and HIFU, respectively. Biochemical thyroid tests and nodules' volume were assessed before and 3, 6 and 12 months after treatments. A thyroid scintigraphy was performed before and 1 year after treatment, respectively. RESULTS The final series included 17 patients treated with RAI and 15 patients treated with HIFU, respectively. Neither demographic nor clinical differences were found at baseline. One year after treatment 14 of 17 RAI-treated and 4 of 15 HIFU-treated patients fulfilled criteria for response to treatment (P = .0008). Indeed, the median TSH value was 1.5 IU/mL and 0.2 IU/mL in HIFU and RAI groups, respectively (P

The blood-brain barrier (BBB), comprised of brain endothelial cells with tight junctions (TJ) between them, regulates the extravasation of molecules and cells into and out of the central nervous system (CNS). Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of a broad range of brain disorders. Current strategies for BBB opening are invasive, not specific, and lack precise control over the site and timing of BBB opening, which may limit their clinical translation. In the present report, we describe a novel approach based on a combination of stem cell delivery, heat-inducible gene expression and mild heating with high-intensity focused ultrasound (HIFU) under MRI guidance to remotely permeabilize BBB. The permeabilization of the BBB will be controlled with, and limited to where selected pro-inflammatory factors will be secreted secondary to HIFU activation, which is in the vicinity of the engineered stem cells and consequently both the primary and secondary disease foci. This therapeutic platform thus represents a non-invasive way for BBB opening with unprecedented spatiotemporal precision, and if properly and specifically modified, can be clinically translated to facilitate delivery of different diagnostic and therapeutic agents which can have great impact in treatment of various disease processes in the central nervous system.

A novel technique for measurement of high intensity focused ultrasound output power of a transducer was introduced in this study. A needle point hydrophone, which was fixed in the pre-focal region of the transducer by a scanning system, was used to measure the acoustic pressure in both amplitude and phase. By using sound pressure method, the predicated power at pocus was calculated and compared with the actual measured one. It was found that the uncertainty between the measured and calculated acoustic power was about 10%. The near field measurement method is applicable to the evaluation of the focused transducer, and it can avoid the damage to measuring equipment of direct measurement.

High intensity focused ultrasound is a thermal therapy method used to treat malignant tumors and other medical conditions. Focused ultrasound concentrates acoustic energy at a focal zone. There, temperature rises rapidly over 56 °C to provoke tissue necrosis. Device performance depends on its fabrication placing computational modeling as a powerful tool to anticipate experimentation results. Finite element method allows modeling of multiphysics systems. Therefore, induced heating was modeled considering the acoustic field produced by a concave radiator excited with electric potentials from 5 V to 20 V. Nonlinear propagation was neglected and a linear response between the acoustic fields and pressure distribution was obtained. Finally, the results showed that acoustic propagation and heating models should be improved and validated with experimental measurements.

The heating effect produced by a focused ultrasound transducer has been investigated by using visual techniques with a positioning system. Ultrasound power, distance, frequency and harmonics of heating effect was investigated. Three experiments were performed on TMM (Tissue Mimicking Material), sheep liver and sheep lung. HIFU (High Intensity Focused Ultrasound) transducer with a resonance frequency of 1.1 MHz and 3.3 MHz was used as source. Effect of ultrasound in liver and lung's pieces were displayed and dimension of cauterization has been measured. Previous temperature measurement results for TMM were compared with liver and lung measurement results so that it is possible to transfer the laboratory measurements to the clinical studies. All measurements were carried out in the system at TUBITAK UME (The Scientific and Technological Research Council of Turkey, the National Metrology Institute) Ultrasound laboratory. (C) 2015 The Authors. Published by Elsevier B.V.

The drug release triggered thermally by high intensity focused ultrasound (HIFU) has been considered a promising drug delivery strategy due to its localized energy and non-invasive characters. However, the mechanism underlying the HIFU-mediated drug delivery remains unclear due to its complexity at the cellular level. In this paper, micro-HIFU (MHIFU) generated by a microfluidic device is introduced which is able to control the drug release from temperature-sensitive liposomes (TSL) and evaluate the thermal and mechanical effects of ultrasound on the cellular drug uptake and apoptosis. By simply adjusting the input electrical signal to the device, the temperature of sample can be maintained at 37 °C, 42 °C and 50 °C with the deviation of ± 0.3 °C as desired. The flow cytometry results show that the drug delivery under MHIFU sonication leads to a significant increase in apoptosis compared to the drug release by incubation alone at elevated temperature of 42 °C. Furthermore, increased squamous and protruding structures on the surface membrane of cells were detected by atomic force microscopy (AFM) after MHIFU irradiation of TSL. We demonstrate that compared to the routine HIFU treatment, MHIFU enables monitoring of in situ interactions between the ultrasound and cell in real time. Furthermore, it can quantitatively analyze and characterize the alterations of the cell membrane as a function of the treatment time.

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.

Background The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. Methods Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients’ data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. Results In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C. Conclusions The TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60–90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ 2, and Cochran’s Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias. The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ 2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1–64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76–86). HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

Objective:Cavitation and coagulation necrosis due to high temperature caused by application of the high intensity focused ultrasound (HIFU) to a focal area occurs. This feature makes HIFU possible to use in the destruction of cancerous tissue. In this study, it was aimed to determine the effect of HIFU on Balb/c mice with Ehrlich ascites tumor model to reach effective usage of HIFU with its clinical and experimental applications in various types of cancer.Methods:Ehrlich ascites tumor cells were obtained from the intraperitoneal region of a donor mouse. Fresh ehrlich ascites tumor cells were injected into 24 mice that were randomly distributed after tumor formation as a control (Group 1), sham treatment (Group 2) and HIFU treatment (Group 3). HIFU application was performed under ultrasound image until conversion of the hypoechoic tumor tissues to hyperechoic appearances. Tumor size and volumes were measured.Results:Tumor sizes and volumes in all groups showed an increase after the treatment. Pathologically all tumors were solid carcinoma with an expansive growth pattern. Necrosis percentages in Group 1, Group 2 and Group 3 were 70±9.6, 70±9.4 and 75.6±4.17, respectively. With regard to Volume 2, there were significant differences between Group 2 and both Group 1 and 3 (p=0.004 and p=0.0001, respectively).Discussion:High intensity focused ultrasound is an effective method in Ehrlich ascites tumor model via prevention of tumor growth and production of necrosis. To achieve a reduction in tumor volume, increasing the duration of HIFU treatment and/or repeatedly application of the treatment is thought to be effective.

Contains fulltext : 173111.pdf (Publisher’s version ) (Closed access) Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2 h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500 ± 10%). For the more compact growing EL4 and 9464D tumors this was 95 ± 13% and 55 ± 33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without major hemorrhages. However, treatment settings may need to be adjusted to the tissue characteristics for optimal tissue fragmentation.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) is a noninvasive thermal technique that enables rapid heating of a specific area in the human body. Its clinical relevance has been proven for the treatments of soft tissue tumors, like uterine fibroids, and for the treatments of solid tumors in bone. In MR-HIFU treatment, MR-thermometry is used to monitor the temperature evolution in soft tissue. However, this technique is currently unavailable for bone tissue. Computer models can play a key role in the accurate prediction and monitoring of temperature. Here, we present a computer ray tracing model that calculates the heat production density in the focal region. This model accounts for both the propagation of shear waves and the interference between longitudinal and shear waves. The model was first compared with a finite element approach which solves the Helmholtz equation in soft tissue and the frequency-domain wave equation in bone. To obtain the temperature evolution in the focal region, the heat equation was solved using the heat production density generated by the raytracer as a heat source. Then, we investigated the role of the interaction between shear and longitudinal waves in terms of dissipated power and temperature output. The results of our model were in agreement with the results obtained by solving the Helmholtz equation and the frequency-domain wave equation, both in soft tissue and bone. Our results suggest that it is imperative to include both shear waves and their interference with longitudinal waves in the model when simulating high intensity focused ultrasound propagation in solids. In fact, when modeling HIFU treatments, omitting the interference between shear and longitudinal waves leads to an over-estimation of the temperature increase in the tissues.

The concept of ideal tumor surgery is to remove the neoplastic tissue without damaging adjacent normal structures. High-intensity focused ultrasound (HIFU) was developed in the 1940s as a viable thermal tissue ablation approach. In clinical practice, HIFU has been applied to treat a variety of solid benign and malig- nant lesions, including pancreas, liver, prostate, and breast carcinomas, soft tissue sarcomas, and uterine fibroids. More recently, magnetic resonance guidance has been applied for treatment monitoring during focused ultrasound procedures (magnetic resonance-guided focused ultra- sound, MRgFUS). Intraoperative magnetic resonance imaging provides the best possible tumor extension and dynamic control of energy deposition using real-time magnetic resonance imaging thermometry. We introduce the fundamental principles and clinical indications of the MRgFUS technique; we also report different treatment options and personal outcomes.

Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on multiparametric magnetic resonance imaging (MRI) were treated with magnetic resonance-guided focused ultrasound (MRgFUS) ablation before radical prostatectomy (RP). An endorectal probe featuring a phased-array focused ultrasound transducer was positioned for lesion ablation under MRI guidance. The tissue temperature and accumulation of thermal damage in the target zone was monitored during the procedure by MRI thermometry. Overlap between the ablation area and the devascularisation of the target lesion was evaluated by contrast-enhanced MRI performed immediately after treatment. The procedure was uneventful, and no adverse events were observed. RP was safely performed without significant surgical difficulties in relation to the previous MRgFUS treatment. The histopathology report showed extensive coagulative necrosis, with no residual tumour in the ablated area. Significant bilateral residual tumour, not evident on pretreatment MRI, was observed outside the treated area in two patients. MRgFUS ablation of focal localised PCa is feasible and, if confirmed in appropriate studies, could represent a valid option for the focal treatment of localised PCa.

We have developed a non-invasive ultrasound theragnostic system (NIUTS) that tracks and follows the movement of an affected area (kidney stone/tumor, in this study) while irradiating it with high-intensity focused ultrasound (HIFU). In this paper, we propose a method to simplify extracting, tracking and following, monitoring the affected area by using a bed-type non-invasive ultrasound theragnostic system.

Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.

Background Although high intensity focused ultrasound (HIFU) is a promising technology for tumor treatment, a moving abdominal target is still a challenge in current HIFU systems. In particular, respiratory‐induced organ motion can reduce the treatment efficiency and negatively influence the treatment result. In this research, we present: (1) a methodology for integration of ultrasound (US) image based visual servoing in a HIFU system; and (2) the experimental results obtained using the developed system. Materials and methods In the visual servoing system, target motion is monitored by biplane US imaging and tracked in real time (40 Hz) by registration with a preoperative 3D model. The distance between the target and the current HIFU focal position is calculated in every US frame and a three‐axis robot physically compensates for differences. Because simultaneous HIFU irradiation disturbs US target imaging, a sophisticated interlacing strategy was constructed. Results In the experiments, respiratory‐induced organ motion was simulated in a water tank with a linear actuator and kidney‐shaped phantom model. Motion compensation with HIFU irradiation was applied to the moving phantom model. Based on the experimental results, visual servoing exhibited a motion compensation accuracy of 1.7 mm (RMS) on average. Moreover, the integrated system could make a spherical HIFU‐ablated lesion in the desired position of the respiratory‐moving phantom model. Conclusions We have demonstrated the feasibility of our US image based visual servoing technique in a HIFU system for moving target treatment.

This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues.

This work extends the quasi-equilibrium relaxation theory of sound absorption in liquids to the case of continuous distribution of relaxation times. Such extension is needed when absorption mechanisms are not confined to the action of viscosity and heat conduction, but are mainly due to the excitation of a large number of internal molecular degrees of freedom. In this case the conventional Navier–Stokes equations are not sufficient to describe the fluid motion, and additional equations are required to model normal relaxation stresses. When relaxation frequencies form a sufficiently dense distribution, as is the case for many biological fluids, it makes sense to consider the limit of continuously distributed relaxation frequencies, in order to obtain the required equation for normal relaxation stresses. In contrast to its discrete counterparts, the proposed method avoids the use of a potentially infinite number of relaxation equations for a given set of distinct relaxation frequencies. Instead, these are replaced by a single evolution equation of Boltzmann type whose right-hand side is a linear combination of the time derivatives of density and entropy. The rheological functions appearing before these derivatives are expressed in terms of the absorption coefficient. Since the dependence of absorption coefficient on sound frequency is measurable experimentally, these rheological coefficients can be recovered from experimental data. The key feature of the present study is that a closed system of equations of motion can be formulated directly from absorption measurement data on the basis of the theory proposed for the very wide range of absorption laws that can occur in practice. As an illustration of the generality of the present method, a number of absorption laws documented in the experimental literature are considered in detail, in order to derive the coefficients of the related systems of equations of motion for these liquids. For example, the methodology based on modelling of acoustic absorption in biologically soft tissue by the employment of fractional derivatives, which has been recently developed in the literature, is shown to be a special case of the proposed theory.

Background: During the past few decades, high-intensity focused ultrasound (HIFU) modality has been gaining surging interest in various therapeutic applications such as non- or minimally-invasive cancer treatment. Among other attributes, robust and real-time HIFU treatment monitoring and lesion detection have become essential issues for successful clinical acceptance of the modality. More recently, ultrasound radio frequency (RF) time series imaging has been studied by a number of researchers. Materials and Methods: The objective of this study is to investigate the applicability of entropy parameter of RF time series of ultrasound backscattered signals, a. k. a. Entropy imaging, toward HIFU thermal lesion detection. To this end, five fresh ex vivo porcine muscle tissue samples were exposed to HIFU exposures with total acoustic powers ranging from 30 to 110 Watts. The contrast-to-speckle ratio (CSR) values of the entropy images and their corresponding B-mode images of pre-, during- and post-HIFU exposure for each acoustic power were calculated. Results: The novelty of this study is the use of Entropy parameter on ultrasound RF time series for the first time. Statistically significant differences were obtained between the CSR values for the B mode and entropy images at various acoustic powers. In case of 110 Watt, a CSR value 3.4 times higher than B-mode images was accomplished using the proposed method. Furthermore, the proposed method is compared with the scaling parameter of Nakagami imaging and same data which are used in this study. Conclusion: Entropy has the potential for using as an imaging parameter for differentiating lesions in HIFU surgery.

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.

Bursts of focused ultrasound energy a thousand times more intense than diagnostic ultrasound have become a non-invasive option for treating cancer, from breast to prostate or uterine fibroid, during the last decade. Despite this progress, many issues still need to be addressed. First, the distortions caused by defocusing obstacles, such as the skull or ribs, on the ultrasonic therapeutic beam are still being investigated. Multi-element transducer technology must be used in order to achieve such transcranial or transcostal adaptive focusing. Second, the problem of motion artifacts, a key component in the treatment of abdominal lesions, has been shown significantly to influence the efficacy and treatment time. Though many methods have been proposed for the detection of organ motion, little work has been done to develop a comprehensive solution including motion tracking and feedback correction in real time. This paper is a review of the work achieved by authors in transcranial high-intensity focused ultrasound (HIFU), transcostal HIFU and motion compensated HIFU. For these three issues, the optimal solution can be reached using the same technology of multi-element transducers devices able to work both in transmit and receive modes.

The aim of this work is to evaluate measurement methods for dosimetry and exposimetry quantities that were developed in the EMRP project "Dosimetry for Ultrasound Therapy - DUTy" by comparing the measurement results for three common quantities from three national laboratories. It further aims to investigate the general feasibility of possible future (key) comparisons for dosimetry and exposimetry quantities and to identify possible open challenges towards this goal. The general format is similar to a metrological comparison, with which the National Metrological Institutes, NMIs, are already familiar. The first step involved the agreement of the protocol that was to specify the set of transducers to be circulated and the measurement conditions. Two transducers were circulated and different drive voltage levels and pulsing regimes were defined and tissue mimicking materials (TMMs) characteristics were specified. Each lab was asked to prepare the TMMs for their own measurements with the inclusion of formulations and preparation instructions specified in the protocol. Uncertainties of the input data were to be declared by the participating laboratories. (C) 2015 The Authors. Published by Elsevier B.V.

Objective: To analysis retrospectively the one year survives of patients with inoperable pancreatic cancer treated by high intensity focused ultrasound by a multiple-center clinical trial. Materials and Methods: From January 2013 to January 2014, 32 patients with un-operative pancreatic cancer from China and Bulgaria were involved into the trial. They are M/F=20/12, aged 59.8±9.1(41-81) years. The size of tumor is 39.3±9.6(20-60)mm. the number of patient with/without metastasis are 18/14.The treatment protocol is HIFU or HIFU plus Chemotherapy. The complications, pain levels and survives were recorded after HIFU. The overall survival rate(OS) and median survival time(MST) were calculated by Kaplan-Meier method, and the differences between patients with/without adjuvant chemotherapy or metastasis were compared with log-rank method. Results: Two cases with degree Ⅱ° skin burn are recorded in 1 month post-HIFU who were cured in 1-2 weeks with conservative treatment. Compared between pre-HIFU and post-HIFU among the 30 cases with pancreatic cancer related pain, the pain levels got released in 24 cases (80.0%), no changed in 5 cases(16.7%), worse in 1 case(3.3%). The OS of all cases in 1 year is 38.4%, MST is 12 months. The OS of patients accepted HIFU plus adjuvant chemotherapy/HIFU in 1 year are 57.4% and 20.8%, MST are 12 months and 6 months, respectively and with difference significantly. The OS of patients with/without metastasis are 0% and 49.2%, MSTs are 7 months and 12 months, respectively and without difference significantly. Conclusion: Both patients from China and Bulgaria with un-operative pancreatic cancer fulfill the HIFU safely. The OS and MST of 1 year are better than other non-operative methods. HIFU plus adjuvant chemotherapy benefits to the survival, while metastasis is a poor prognosis factor.

High-intensity focused ultrasound (HIFU) has been emerging as an effective and noninvasive modality in cancer treatment with very promising clinical results. However, a small vessel in the focal region could be ruptured, which is an important concern for the safety of HIFU ablation. In this study, lesion formation in the polyacrylamide gel phantom embedded with different tubing (inner diameters of 0.76 mm and 3 mm) at varied flow speeds (17–339 cm/s) by HIFU ablation was photographically recorded. Produced lesions have decreased length (~30%) but slightly increased width (~6%) in comparison to that without the embedded tubing. Meanwhile, bubble activities during the exposures were measured by passive cavitation detection (PCD) at the varied pulse repetition frequency (PRF, 10–30 Hz) and duty cycle (DC, 10%-20%) of the HIFU bursts. High DC and low flow speed were found to produce stronger bubble cavitation whereas no significant influence of the PRF. In addition, high-speed photography illustrated that the rupture of tubing was produced consistently after the first HIFU burst within 20 ms and then multiple bubbles would penetrate into the intraluminal space of tubing through the rupture site by the acoustic radiation force. Alignment of HIFU focus to the anterior surface, middle, and posterior surface of tubing led to different characteristics of vessel rupture and bubble introduction. In summary, HIFU-induced vessel rupture is possible as shown in this phantom study; produced lesion sizes and shapes are dependent on the focus alignment to the tubing, flow speed, and tubing properties; and bubble cavitation and the formation liquid jet may be one of the major mechanisms of tubing rupture as shown in the high-speed photography. Published version