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Rationale and Objectives: To investigate whether the quantitative index of signal intensity (SI) heterogeneity on T2-weighted (T2W) magnetic resonance images can predict the difficulty and efficacy of high-intensity focused ultrasound (HIFU) ablation for uterine fibroids., Materials and Methods: The standard deviation (SD) of T2W image (T2WI) SI was used to quantify SI heterogeneity. The correlation between SD and the non-perfused volume ratio (NPVR) in 575 patients undergoing HIFU treatment was retrospectively analyzed, and the efficacy of SD in predicting NPVR was discussed. Three classifications were made based on the SD, and the ablation difficulty and ablation effect of different grades were compared. A total of 65 cases from another center were used as an external validation set to verify the classification performance of SD., Results: The SD of SI was negatively correlated with NPVR (r = -0.460, p < 0.001). The predictive efficiency of SD for the ablation effect was higher than that of the scaled signal intensity (0.767 vs. 0.701, p = 0.006). Univariate and multivariate logistic regression analyses showed that SD was an independent predictor of ablation effect. Based on SD, the three classifications were divided into SD I: SD < 101.0, SD II: 101.0 ≤ SD < 138.7, and SD III: SD≥ 138.7. The treatment time, sonication time, treatment intensity, and total energy of SD I were lower than those of SD II and III (p < 0.05)., Conclusion: The heterogeneity of T2WI SI of uterine fibroids is negatively correlated with NPVR. The SD of SI can be used to predict the ablation difficulty and ablation effect of HIFU., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation., Methods: In-vivo Achilles tendons (hybrid N  = 15, thermal ablation alone N  = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first ( N  = 21) was ablation (600, 900, or 1200 J). The second ( N  = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups., Results: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability., Conclusion: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.

Primary trigeminal neuralgia is a common clinical refractory neuralgia characterized by an onset of excruciating pain that can severely affect patients' quality of life. Long-term suffering from this pain may lead to depression, anxiety, and suicide. Current treatments, however, are associated with high recurrent rates and severe complications. We hypothesize that both the applicability and efficacy of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment in primary trigeminal neuralgia can be achieved under the following conditions: a specific target focus and incident channel, a temperature measurement system that does not incur damage to surrounding tissues, and an optimal radiation dose. Successful non-invasive treatment of primary trigeminal neuralgia by MR-HIFU systems could represent a breakthrough of this technology applied to the oral and maxillofacial region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Stomatological Hospital of Chongqing Medical University. Published by Elsevier Ltd.. All rights reserved.)

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 <70% were 91.7% and 52.6%, respectively ( p  = 0.0235). Conclusion: The pretreatment KPS was an independent prognostic factor for clinical responses, and lesion CVF was an independent prognostic factor for radiographic responses.

Purpose: In local hyperthermia, precise temperature control throughout the entire target region is key for swift, safe, and effective treatment. In this article, we present a model predictive control (MPC) algorithm providing voxel-level temperature control in magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) and assess the improvement in performance it provides over the current state of the art. Materials and methods: The influence of model detail on the prediction quality and runtime of the controller is evaluated and a tissue mimicking phantom is characterized using the resulting model. Next, potential problems arising from modeling errors are evaluated in silico and in the characterized phantom. Finally, the controller's performance is compared to the current state-of-the-art hyperthermia controller in side-by-side experiments. Results: Modeling diffusion by heat exchange between four neighboring voxels achieves high predictive performance and results in runtimes suited for real-time control. Erroneous model parameters deteriorate the MPC's performance. Using models derived from thermometry data acquired during low powered test sonications, however, high control performance is achieved. In a direct comparison with the state-of-the-art hyperthermia controller, the MPC produces smaller tracking errors and tighter temperature distributions, both in a homogeneous target and near a localized heat sink. Conclusion: Using thermal models deduced from low-powered test sonications, the proposed MPC algorithm provides good performance in phantoms. In direct comparison to the current state-of-the-art hyperthermia controller, MPC performs better due to the more finely tuned heating patterns and therefore constitutes an important step toward stable, uniform hyperthermia.

Objective: To develop and evaluate a combined motion-assisted/gated MRHIFU heating strategy designed to accelerate the treatment procedure by reducing the required number of sonications to ablate a target volume in the pancreas. Methods: A planning method for combined motion-assisted/gated MRHIFU using 4D-MRI and motion characterization is introduced. Six healthy volunteers underwent 4D-MRI for target motion characterization on a 3.0-T clinical scanner. Using displacement patterns, simulations were performed for all volunteers for three sonication approaches: gated, combined motion-assisted/gated, and static. The number of sonications needed to ablate the pancreas head was compared. The influence of displacement amplitude and target volume size was investigated. Spherical target volumes (8, 15, 20 and 34 mL) and displacement amplitudes ranging from 5 to 25 mm were evaluated. For this case, the number of sonications required to ablate the whole target was determined. Results: The number of required sonications was lowest for a static target, 62 on average (range 49-78). The gated approach required most sonications, 126 (range 97-159). The combined approach was almost as efficient as the hypothetical static case, with an average of 78 (range 53-123). Simulations showed that with a 5-mm displacement amplitude, the target could be treated by making use of motion-assisted MRHIFU sonications only. In that case, this approach allowed the lowest number of sonication, while for 10 mm and above, the number of required sonications increased. Conclusion: The use of a combined motion-assisted/gated MRHIFU strategy may accelerate tumor ablation in the pancreas when respiratory-induced displacement amplitudes are between 5 and 10 mm.

Background: The use of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) to deliver mild hyperthermia requires stable temperature mapping for long durations. This study evaluates the effects of respiratory motion on MR thermometry precision in pediatric subjects and determines the in vivo feasibility of circumventing breathing-related motion artifacts by delivering MR thermometry-controlled HIFU mild hyperthermia during repeated forced breath holds. Materials and methods: Clinical and preclinical studies were conducted. Clinical studies were conducted without breath-holds. In phantoms, breathing motion was simulated by moving an aluminum block towards the phantom along a sinusoidal trajectory using an MR-compatible motion platform. In vivo experiments were performed in ventilated pigs. MR thermometry accuracy and stability were evaluated. Results: Clinical data confirmed acceptable MR thermometry accuracy (0.12-0.44 °C) in extremity tumors, but not in the tumors in the chest/spine and pelvis. In phantom studies, MR thermometry accuracy and stability improved to 0.37 ± 0.08 and 0.55 ± 0.18 °C during simulated breath-holds. In vivo MR thermometry accuracy and stability in porcine back muscle improved to 0.64 ± 0.22 and 0.71 ± 0.25 °C during breath-holds. MR-HIFU hyperthermia delivered during intermittent forced breath holds over 10 min duration heated an 18-mm diameter target region above 41 °C for 10.0 ± 1.0 min, without significant overheating. For a 10-min mild hyperthermia treatment, an optimal treatment effect (TIR > 9 min) could be achieved when combining 36-60 s periods of forced apnea with 60-155.5 s free-breathing. Conclusion: MR-HIFU delivery during forced breath holds enables stable control of mild hyperthermia in targets adjacent to moving anatomical structures.

Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by delivering a sufficiently high level of acoustic energy in situ of the human body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided (USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for monitoring purposes. The principles and technologies of FUS/HiFU are described in this paper including the basics of MR guidance techniques and MR temperature mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the treatment of various benign and few malignant lesions in the last two decades. Current technical limitations of ultrasound guided and MRI guided Focused Ultrasound, as well as adverse effects for the application of this technique are outlined including challenges of ablating moving organs (liver and kidney). An outlook to possible applications is provided; exampling clinical trials discussing future options.

Objective: To investigate factors affecting effects of ultrasound guided high intensity focused ultrasound (USgHIFU) in the treatment of single uterine fibroids (UFs) with different magnetic resonance imaging (MRI) features., Methods: A total of 207 patients with single symptomatic UFs who were treated with HIFU were retrospectively analyzed. All UFs were grouped according to MRI features, and factors affecting HIFU ablation were set as independent variables. Non-perfusion volume ratio (NPVR) and energy efficiency factor (EEF) were set as dependent variables to establish multiple linear regression models with a stepwise method., Results: All patients had successful HIFU treatment, with the mean NPVR of 74.7 ± 15.1% and the mean EEF of 7.4 ± 5.2 j/mm 3 . The NPVR was negatively correlated with transmural type of UFs, hyperintense on T2 weighted image (T2WI), enhancement type on T1 weighted image (T1WI), distance from UFs ventral side to skin and posterior location of UFs, but positively correlated with anterior location of UFs, hypointense on T2WI and anteverted uterus (uterine location). The EEF was negatively correlated with size, anterior location of UFs and hypointense on T2WI, but positively correlated with distance from UFs ventral side to skin, enhancement type on T1WI and transmural type of UFs. The UFs size and enhancement type on T1WI were the greatest factors affecting the ablation effect., Conclusions: The effect of HIFU treatment for single UFs is affected by multiple factors, and the UFs of hypointense on T2WI, large size, mild enhancement on T1WI and anteverted uterus can be easily ablated with high ablation efficiency.

Purpose: To evaluate the effect of differences in sonication duration and power on the size of postcontrast ablation zone following magnetic resonance-guided focused ultrasound (MRgFUS) of bone in a swine femoral bone model., Materials and Methods: Experimental procedures received approval from the Institutional Committee on Animal Research. MRgFUS was used to create two thermal lesions in the left femur of six pigs. Each target was subjected to six sonications. 400J of energy was used for each sonication. However, the distal target received the standard sonication duration of 20 seconds (20W), while the proximal target received a longer sonication duration of 40 seconds (10W). MRgFUS lesions were imaged with fat-saturated spoiled gradient echo sequence at 3.0T MRI 10 minutes following the administration of contrast. Maximum three-plane dimensions of the hypoenhanced ablation area were measured., Results: Postcontrast MR images demonstrated ovoid regions of hypoenhancement at each target. The average depth of ablation was significantly greater for the shorter high-power sonications (7.3 mm), compared to the longer lower-power sonications (4.5 mm), P = 0.026. The craniocaudal dimension was also greater for the shorter ablations 26.7 mm compared to the longer sonications 21.0 mm, P = 0.006., Conclusion: Contrary to anecdotal clinical experience, this preclinical model suggests that during MRgFUS of bone, standard duration, higher-power sonications resulted in deeper ablation volumes compared to long duration, lower-power sonications. These results suggest that to achieve deeper ablations, if longer sonications are used, then the power should be relatively maintained, for a net energy increase., Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1418-1422., (© 2017 International Society for Magnetic Resonance in Medicine.)

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 2h 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment., Competing Interests: Declarations of Interest The authors report no conflicts of interest.

Boiling histotripsy (BH) is a new high intensity focused ultrasound (HIFU) ablation technique to mechanically fragmentize soft tissue into submicrometer fragments. So far, ultrasound has been used for BH treatment guidance and evaluation. The in vivo histopathological effects of this treatment are largely unknown. Here, we report on an MR guided BH method to treat subcutaneous tumors in a mouse model. The treatment effects of BH were evaluated one hour and four days later with MRI and histopathology, and compared with the effects of thermal HIFU (T-HIFU). The lesions caused by BH were easily detected with T2 w imaging as a hyper-intense signal area with a hypo-intense rim. Histopathological evaluation showed that the targeted tissue was completely disintegrated and that a narrow transition zone (<200 µm) containing many apoptotic cells was present between disintegrated and vital tumor tissue. A high level of agreement was found between T2 w imaging and H&E stained sections, making T2 w imaging a suitable method for treatment evaluation during or directly after BH. After T-HIFU, contrast enhanced imaging was required for adequate detection of the ablation zone. On histopathology, an ablation zone with concentric layers was seen after T-HIFU. In line with histopathology, contrast enhanced MRI revealed that after BH or T-HIFU perfusion within the lesion was absent, while after BH in the transition zone some micro-hemorrhaging appeared. Four days after BH, the transition zone with apoptotic cells was histologically no longer detectable, corresponding to the absence of a hypo-intense rim around the lesion in T2 w images. This study demonstrates the first results of in vivo BH on mouse tumor using MRI for treatment guidance and evaluation and opens the way for more detailed investigation of the in vivo effects of BH. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has become an attractive, non-invasive treatment for benign and malignant tumours, and offers specific benefits for poorly accessible locations in the liver. However, the presence of the ribcage and the occurrence of liver motion due to respiration limit the applicability MRgFUS. Several techniques are being developed to address these issues or to decrease treatment times in other ways. However, the potential benefit of such improvements has not been quantified. In this research, the detailed workflow of current MRgFUS procedures was determined qualitatively and quantitatively by using observation studies on uterine MRgFUS interventions, and the bottlenecks in MRgFUS were identified. A validated simulation model based on discrete events simulation was developed to quantitatively predict the effect of new technological developments on the intervention duration of MRgFUS on the liver. During the observation studies, the duration and occurrence frequencies of all actions and decisions in the MRgFUS workflow were registered, as were the occurrence frequencies of motion detections and intervention halts. The observation results show that current MRgFUS uterine interventions take on average 213min. Organ motion was detected on average 2.9 times per intervention, of which on average 1.0 actually caused a need for rework. Nevertheless, these motion occurrences and the actions required to continue after their detection consumed on average 11% and up to 29% of the total intervention duration. The simulation results suggest that, depending on the motion occurrence frequency, the addition of new technology to automate currently manual MRgFUS tasks and motion compensation could potentially reduce the intervention durations by 98.4% (from 256h 5min to 4h 4min) in the case of 90% motion occurrence, and with 24% (from 5h 19min to 4h 2min) in the case of no motion. In conclusion, new tools were developed to predict how intervention durations will be affected by future workflow changes and by the introduction of new technology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU treatment is most often restricted to contrast-enhanced T1 -weighted imaging, while it has been shown that the non-perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU-induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been-or could be-used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI-based evaluation of HIFU treatment., (© 2015 Wiley Periodicals, Inc.)

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} (R(2) to line of identity (R(2)y=x) = 0.92) and the strongest agreement was seen 3 days after HIFU (R(2)y=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.)

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., (© 2014 Wiley Periodicals, Inc.)

This pilot study compared the detectability of internal thermal marks produced with MRI-guided focused ultrasound (MRgFUS) on MRI, computed tomography (CT), ultrasonography (US), and color images from digital scanning. Internal marks made using MRgFUS could potentially guide surgical, biopsy or radiotherapy procedures. New Zealand White rabbits (n = 6) thigh muscle were marked using a Philips MRgFUS system. Before and after sonications, rabbits were imaged using T1- and T2-weighted MRI. Then rabbits were sacrificed and imaging was performed using CT and US. After surgical excision specimens were scanned for color conspicuity analysis. Images were read by a radiologist and quantitative analysis of signal intensity was calculated for marks and normal muscle. Of a total of 19 excised marks, approximately 79%, 63%, and 62% were visible on MRI, CT, and US, respectively. The average maximum temperature elevation in the marks during MRgFUS was 39.7 ± 10.1 °C, and average dose diameter (i.e., the diameter of the area that achieved a thermal dose greater than 240 cumulative equivalent minutes at 43 °C) of the mark at the focal plane was 7.3 ± 2.1 mm. On MRI the average normalized signal intensities were significantly higher in marks compared to normal muscle (p < 0.05). On CT, the marked regions were approximately 10 HU lower than normal muscle (p < 0.05). The results demonstrate that MRgFUS can be used to create internal marks that are visible on MRI, CT and US., (Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed., Methods: APT imaging was performed on tumor-bearing mice before (n = 15), directly after (n = 15) and at 3 days (n = 8) after HIFU treatment. A control group (n = 7) of nontreated animals was scanned at the same time points. Histogram analysis of the tumor APT-weighted signal distributions was performed to assess HIFU-induced changes in the tumor APT contrast., Results: Distinct regions of decreased APT-weighted signal were observed at both time points after HIFU treatment. Analysis of the tumor APT-weighted signal distribution showed a pronounced shift toward lower APT-weighted signal values after HIFU treatment. A significantly increased fraction of pixels with an APT-weighted signal value between -10 and -2% was observed both directly (0.37 ± 0.16) and at 3 days (0.49 ± 0.16) after HIFU treatment as compared to baseline (0.22 ± 0.16)., Conclusion: The presented results show that APT imaging is sensitive to HIFU-induced changes in tumor tissue and may thus serve as a new biomarker for monitoring the response of tumor tissue to HIFU treatment., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The use of correct tissue thermal diffusivity values is necessary for making accurate thermal modelling predictions during magnetic resonance-guided focused ultrasound (MRgFUS) treatment planning. This study evaluates the accuracy and precision of two non-invasive thermal diffusivity estimation methods, a Gaussian temperature method and a Gaussian specific absorption rate (SAR) method., Materials and Methods: Both methods utilise MRgFUS temperature data obtained during cooling following a short (<25 s) heating pulse. The Gaussian SAR method can also use temperatures obtained during heating. Experiments were performed at low heating levels (ΔT∼10 °C) in ex vivo pork muscle and in vivo rabbit back muscle. The non-invasive MRgFUS thermal diffusivity estimates were compared with measurements from two standard invasive methods., Results: Both non-invasive methods accurately estimated thermal diffusivity when using MR temperature cooling data (overall ex vivo error <6%, in vivo <12%). Including heating data in the Gaussian SAR method further reduced errors (ex vivo error <2%, in vivo <3%). The significantly lower standard deviation values (p < 0.03) of the Gaussian SAR method indicated that it had better precision than the Gaussian temperature method., Conclusions: With repeated sonications, either MR-based method could provide accurate thermal diffusivity values for MRgFUS therapies. Fitting to more data simultaneously likely made the Gaussian SAR method less susceptible to noise, and using heating data helped it converge more consistently to the FUS fitting parameters and thermal diffusivity. These effects led to the improved precision of the Gaussian SAR method.

Purpose: To investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR-guided focal therapy., Materials and Methods: We retrospectively identified 88 patients with biopsy-proven prostate cancer who underwent endorectal MRI and MRS imaging prior to radical prostatectomy with creation of histopathological tumor maps. Two independent readers noted the largest tumor foci at MRI, if visible, and the volume of concordant abnormal tissue at MRS imaging, if present. A logistic random intercept model was used to determine the association between clinical and MR findings and correct identification of treatable (over 0.5 cm3) dominant intraprostatic tumor foci., Results: Readers 1 and 2 identified dominant tumor foci in 50 (57%) and 58 (65%) of 88 patients; 42 (84%) and 48 (83%) of these were dominant treatable lesions at histopathology, respectively. Within the statistical model, the volume of concordant spectroscopic abnormality was the only factor that predicted correct identification of a dominant treatable lesion on T2-weighted images (odds ratio=1.75; 95% confidence interval=1.08 to 2.82; P value=0.02). In particular, all visible lesions on T2-weighted imaging associated with at least 0.54 cm3 of concordant spectroscopic abnormality were correctly identified dominant treatable tumor foci., Conclusion: Patients with dominant intraprostatic tumor foci seen on T2-weighted MRI and associated with at least 0.54 cm3 of concordant MRS imaging abnormality may be radiological candidates for MR-guided focal therapy., (Copyright © 2013 Wiley Periodicals, Inc.)

It has been well known for decades that high intensity focused ultrasound (HIFU) generates heat in tissues resulting in coagulative necrosis. Implementation, however, has been slow, due to difficulties with finding an appropriate imaging modality that could not only guide treatment, but also provide real-time thermal feedback. These problems have been overcome with the newest magnetic resonance-guided high intensity focused ultrasound systems (MRgHIFU). With its superior spatial resolution enabling accurate image guidance coupled with its ability to provide real-time thermography during treatments, MRI is moving further into the realm of therapeutics for oncologic patient care. This article will discuss the implementation of an MR-guided HIFU system, current clinical indications and touch on future directions., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Purpose: The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). Materials and methods: In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. Results: The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). Conclusion: MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor. [ABSTRACT FROM AUTHOR]

PurposeThe ExAblate body MRgFUS system requires advanced beamforming strategies for volumetric hyperthermia. This study aims to develop and evaluate electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation using an acoustic and biothermal simulation framework along with phantom experiments.MethodsThe simulation framework was developed to calculate the 3D acoustic intensity and temperature distribution resulting from various beamforming and scanning strategies. A treatment cell electronically sweeping a single focus was implemented and evaluated in phantom experiments. The acoustic and thermal focal size of vortex beam propagation was quantified according to the vortex modes, number of active array elements, and focal depth.ResultsTurning off a percentage of the outer array to increase the f-number increased the focal size with a decrease in focal gain. 60% active elements allowed generating a sonication cell with an off-axis of 10 mm. The vortex mode number 4 with 60% active elements resulted in a larger heating volume than using the full array. Volumetric hyperthermia in the phantom was evaluated with the vortex mode 4 and respectively performed with 100% and 80% active elements. MR thermometry demonstrated that the volumes were found to be 18.8 and 29.7 cm3, respectively, with 80% array activation producing 1.58 times larger volume than the full array.ConclusionsThis study demonstrated that both electronic beam steering and sector vortex beamforming approaches in conjunction with partial array activation could generate large volume heating for HT delivery using the ExAblate body array.

Objective: To investigate the changes of immunological status and imaging evaluation of high intensity focused ultrasound(HIFU) in the treatment of adenomyosis(AM). Methods: 186 patients with AM admitted to Shijiazhuang People’s Hospital from December 2020 to December 2021 were selected. Before and after HIFU ablation, serum complement C3, C4, the ratio of helper T cell17 to regulatory T cell(Th17/Treg) and magnetic resonance imaging(MRI) were detected.Compare the differences of ultrasound characteristics, MRI measurement parameters, serum complement C3, C4, Th17/Treg levels in AM patients before and after treatment; Spearman correlation was used to analyze the correlation between the levels of serum complement C3, C4, Th17/Treg and the ablation rate and MRI parameters of the non-perfusion area after treatment. Results: Before HIFU treatment in AM patients, ultrasound showed that the echo of the myometrium of the uterine wall was uneven, the blood flow signal of the myometrium was rich, and the blood flow of the focus was rich; MRI showed that the uterus was non-uniformly enlarged, the uterine wall was significantly thickened, the boundary with the uterine junction was unclear, and the signal was uneven. The dynamic enhancement scan showed that the focus was non-uniformly enhanced, and the degree of enhancement was slightly lower than that of the normal myometrium nearby. VAS score of AM patients after HIFU treatment was significantly lower than that before treatment(P＜0.05); Ultrasound showed that the echo of the myometrium of the uterus was uneven, and the blood supply of the myometrium was significantly reduced. MRI showed that the thickening of the uterine wall was reduced, and the signal was uneven. The enhancement scan showed that the central perfusion area was not enhanced, and the peripheral nodular or irregular enhancement was the residual focus, and the ablation rate was about 90%. After HIFU treatment, the levels of serum complement C3 and C4, ADC value and MSI value of residual lesions increased significantly(P＜0.05), while Th17/Treg,ADC value and MSI value of non-perfusion zone decreased significantly(P＜0.05). After HIFU treatment, serum complement C3 and C4levels were significantly negatively correlated with ablation rate, ADC value and MSI value in non-perfusion zone(P＜0.05), while Th17/Treg was significantly positively correlated with ablation rate, ADC value and MSI value in non-perfusion zone(P＜0.05). Conclusion: The changes of immunologic status and MRI evaluation after HIFU treatment of AM patients can help predict the prognosis of AM patients, and guide clinicians to provide objective and realistic basis for the choice of follow-up treatment plan for AM patients. [ABSTRACT FROM AUTHOR]

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.

Uterine fibroids are the most common benign uterine tumours in women of reproductive age. They can present with different symptoms, including menorrhagia, cramping lower abdominal pain, bloating, urinary/bowel symptoms, spotting, and infertility. Management could be medical and surgical. Other options include uterine artery embolization and non-invasive treatment with high-intensity focused ultrasound (HIFU). We present a case of a 32-year-old woman with menorrhagia and severe pelvic pain. Ultrasound examination revealed an intramural myoma measuring 93x98x87 mm. The patient signed informed consent for HIFU ablation of the fibroid. Three months after the procedure, an MRI scan showed the fibroid had shrunk to 75% of its original size with dimensions 32x35x29. After six months, she became pregnant and gave birth to a healthy infant at 38-weeks gestation with caesarean section, at which point the fibroid measured 2 cm. HIFU is an alternative to surgical therapies and is highly beneficial in women wishing for future pregnancies. Preserving the option for future pregnancies in patients with uterine fibroids is only one of its benefits and might be the key solution for these women. HIFU treatment of uterine fibroids is an innovative approach. It should be encouraged: it is widely adopted in similar cases where it has positively impacted the treatment of uterine fibroids. [ABSTRACT FROM AUTHOR]

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 24h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.

AimTo use magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU), magnetic resonance imaging (MRI) and histopathology for noninvasively ablating, quantifying and characterizing ablated renal tissue.MethodsSix anesthetized/mechanically-ventilated pigs underwent single/double renal sonication (n = 24) using a 3T-MRg-HIFU (1.1 MHz frequency and 3000J-4400J energies). T2-weighted fast spin echo (T2-W), perfusion saturation recovery gradient echo and contrast enhanced (CE) T1-weighted (T1-W) sequences were used for treatment planning, temperature monitoring, lesion visualization, characterization and quantification, respectively. Histopathology was conducted in excised kidneys to quantify and characterize cellular and vascular changes. Paired Student's t-test was used and a P-value < 0.05 was considered statistically significant.ResultsAblated renal parenchyma could not be differentiated from normal parenchyma on T2-W or non-CE T1-W sequences. Ablated renal lesions were visible as hypoenhanced regions on perfusion and CE T1-W MRI sequences, suggesting perfusion deficits and necrosis. Volumes of ablated parenchyma on CE T1-W images in vivo (0.12-0.36 cm(3) for single sonication 3000J, 0.50-0.84 cm(3), for double 3000J, 0.75-0.78 cm(3) for single 4400J and 0.12-2.65 cm(3) for double 4400J) and at postmortem (0.23-0.52 cm(3), 0.25-0.82 cm(3), 0.45-0.68 cm(3) and 0.29-1.80 cm(3), respectively) were comparable. The ablated volumes on 3000J and 4400J double sonication were significantly larger than single (P < 0.01), thus, the volume and depth of ablated tissue depends on the applied energy and number of sonication. Macroscopic and microscopic examinations confirmed the locations and presence of coagulation necrosis, vascular damage and interstitial hemorrhage, respectively.ConclusionContrast enhanced MRI provides assessment of MRg-HIFU renal ablation. Histopathology demonstrated coagulation necrosis, vascular damage and confirmed the volume of damage seen on MRI.

To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids. 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center. According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas. Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner. [ABSTRACT FROM AUTHOR]

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.

Objective: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. Methods: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). Results: Successful technical treatments were achieved in 80 $\%$ of the patients. All patients underwent the treatment with no sedation and 60 $\%$ of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 $\pm$ 1.8 mm while 6.2 $\pm$ 1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 $\%$ and 70 $\%$ of patients, respectively. Conclusion: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts. [ABSTRACT FROM AUTHOR]

Theranostic nanocarriers of antivascular drug encapsulated in thermosensitive ultramagnetic liposomes can be advantageously designed to provide a locally high concentration and an active delivery, with image-guided Magnetic Resonance Imaging (MRI) so as to reliably cure tumor. We propose a novel therapeutic strategy consisting of the magnetic accumulation of Ultra Magnetic Liposomes (UML) followed by High-Intensity Focused Ultrasound (HIFU) to trigger the release of an antivascular agent monitored by MRI. For this purpose, we co-encapsulated Combretastatin A4 phosphate (CA4P), a vascular disrupting agent, in the core of UML to obtain CA4P-loaded thermosensitive Ultra Magnetic Liposomes (CA4P-UML). To assess the HIFU parameters, the CA4P release has been triggered in vitro by local heating HIFU at the lipids transition temperature. Morphology of endothelial cells was assessed to evaluate the effect of encapsulated versus non-encapsulated CA4P. The efficiency of a treatment combining the magnetic targeting of CA4P-UML with the CA4P release triggered by HIFU was studied in CT26 murine tumors. Tumor perfusion and volume regression parameters were monitored by multiparametric quantitative anatomical and dynamic in vivo MRI at 7 T. Additionally, vascularization and cellularity were evaluated ex-vivo by histology. This thorough investigation showed that the combined treatment exhibited a full benefit. A 150-fold improvement compared with the chemotherapy alone was obtained using a magnetic targeting of CA4P-UML triggered by HIFU, and was consistent with an expected effect on vascularization 24 h after treatment. Unlabelled Image • First magnetic thermosensitive liposomes encapsulating CA4P and magnetic nanoparticles. • Proof of concept of combined magnetic targeting + HIFU-drug release with CA4P-magnetic liposomes. • Similar efficacy of targeted liposomes encapsulating CA4P as the free drug at a 150 lower dose. • MRI Engineering to evidence the efficiency of a novel theranostic liposome. [ABSTRACT FROM AUTHOR]

During high-intensity focused ultrasound (HIFU) therapy, it is important that the electrical power delivered to the transducer is monitored to avoid underexposure or overexposure, ensure patient safety, and to protect the transducer itself. Due to ease of measurement, the transducer’s potential difference may be as an indicator of power delivery. However, even when a transducer’s complex impedance is well characterized at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path, or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as a magnetic resonance imaging (MRI)-compatible, miniature alternative to bidirectional power couplers, which is compatible with switched amplifiers. For CCV power measurement, current probe data were multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers, there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery, leading to safer HIFU treatments. [ABSTRACT FROM AUTHOR]

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 (n¼75) 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. [ABSTRACT FROM AUTHOR]

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 <70% were 91.7% and 52.6%, respectively (p = 0.0235). Conclusion: The pretreatment KPS was an independent prognostic factor for clinical responses, and lesion CVF was an independent prognostic factor for radiographic responses. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between magnetic resonance (MR) T1 perfusion-based classification and the outcome of MR-guided high intensity focused ultrasound treatment of adenomyosis, defined as nonperfused volume (NPV) ratio. Methods: The adenomyosis of 31 women was classified into group A (time-signal intensity [SI] curve of adenomyosis lower than that of the myometrium) and group B (time-SI curve of adenomyosis equal to or higher than that of the myometrium) on the basis of time-SI curves on dynamic contrast enhanced (DCE) MR images acquired at screening. NPV ratios immediately after treatment and adenomyosis volume reduction ratios and symptom severity scores (SSS) at the six-month follow-up were retrospectively assessed. Univariate and multivariate analysis of pretreatment parameters conducted to assess independent factors impacting on immediate NPV ratio. All adverse effects were recorded. Results: The immediate NPV ratios in groups A and B were 89.2 ± 6.7% and 42.4 ± 19.0%, respectively. At the six-month follow-up, the adenomyosis volume reduction ratios in groups A and B were 0.27 ± 0.8 and 0.04 ± 0.1, respectively, with corresponding improvements of 0.7 ± 0.18 and 0.26 ± 0.25, respectively, in the mean transformed SSS. Univariate and multivariate analysis revealed that only T1 perfusion-based classification as an independent factor associated with the outcome of MR-guided high intensity focused ultrasound treatment. No serious adverse effects were reported. Conclusions: Our novel classification method introduced in this study might be clinically beneficial in classifying adenomyosis for predicting the immediate outcome of MR-guided high intensity focused ultrasound treatment. [ABSTRACT FROM AUTHOR]

Adenomyosis is a disorder of uterus in which endometrial glands and stroma are present within the uterine musculature. The main clinical manifestations are dysmenorrhea and menorrhagia. Adenomyosis has a great impact on both the quality of life and fertility of women. The treatment of adenomyosis remains an immense challenge. Relevant articles were searched through MEDLINE and PubMed between 2000 and March 2017. The search terms of adenomyosis, magnetic resonance imaging (MRI) features of adenomyosis, high intensity focused ultrasound (HIFU), ultrasound-guided HIFU and MRgFUS were used. There were no language restrictions. HIFU is a non-invasive local thermal ablation technique which has been used in the treatment of both focal and diffuse adenomyosis. Several case studies have demonstrated that HIFU presents low rate of minor and/or major complications and, at the same time, a long symptom-relief period. Multiple factors such as the enhancement type of the adenomyotic lesion, volume of the adenomyotic lesions, number of hyperintense foci on T2WI, location of the uterus, location of adenomyotic lesions, thickness of the abdominal wall and distance from the skin to the adenomyotic lesions contribute to the efficacy of HIFU. Consequently, based on these contributing factors, specific and strict selection criteria have been used to achieve higher efficacy. Thus, patients with pelvic endometriosis, adhesions between the bowel and the uterus, or an abdominal surgical scar wider than 10 mm, are not suitable for HIFU treatment. Moreover, HIFU-treated patients with adenomyosis, who wished to conceive, showed high conception and live birth rates. HIFU is a new and promising treatment option for patients with adenomyosis, but its efficacy, safety, cost-effectiveness and fertility outcome must be evaluated by randomized controlled trials. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm³ was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU. [ABSTRACT FROM AUTHOR]

Combination of polymer therapeutics and hyperthermia has been shown to enhance accumulation in selectively heated tumor tissue. The additional use of heat shock (HS)-targeting towards tumor tissues can further enhance accumulation and retention, and improve therapeutic outcomes. In this work, high intensity focused ultrasound (HIFU) was used to generate hyperthermia in prostate tumor tissue. Upregulation of the cell surface HS receptor glucose regulated protein 78 kDa (GRP78) was observed after treatment with HIFU hyperthermia which was then targeted by specific HS-targeting peptides. We used the peptide sequence WDLAWMFRLPVG attached to the side chains of water-soluble N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing docetaxel (DOC) conjugated via a lysosomally degradable linker. It was shown that HIFU-mediated HS-targeted copolymer–DOC conjugates improved treatment efficacy in a murine prostate tumor xenograft model. These results show that the use of HIFU hyperthermia in combination with HS-targeted polymer–drug conjugates has potential to improve therapeutic outcomes in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Mild hyperthermia has been used in combination with polymer therapeutics to further increase delivery to solid tumors and enhance efficacy. An attractive method for generating heat is through non-invasive high intensity focused ultrasound (HIFU). HIFU is often used for ablative therapies and must be adapted to produce uniform mild hyperthermia in a solid tumor. In this work a magnetic resonance imaging guided HIFU (MRgHIFU) controlled feedback system was developed to produce a spatially uniform 43 °C heating pattern in a subcutaneous mouse tumor. MRgHIFU was employed to create hyperthermic conditions that enhance macromolecular delivery. Using a mouse model with two subcutaneous tumors, it was demonstrated that MRgHIFU enhanced delivery of both Evans blue dye (EBD) and Gadolinium-chelated N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers. The EBD accumulation in the heated tumors increased by nearly 2-fold compared to unheated tumors. The Gadolinium-chelated HPMA copolymers also showed significant enhancement in accumulation over control as evaluated through MRI T1-mapping measurements. Results show the potential of HIFU-mediated hyperthermia for enhanced delivery of polymer therapeutics. [ABSTRACT FROM AUTHOR]

Purpose:Phase-sensitive optical coherence tomography (PhS-OCT) is proposed, as a new high intensity focused ultrasound (HIFU) imaging guidance to detect and track HIFU focus inside 1% agar samples in this work. The experiments studied the effect of varying HIFU power on the induction of shear wave, which can be implemented as a new technique to monitor focused ultrasound surgery (FUS). Method:A miniature HIFU transducer (1.02 MHz, 20 mm aperture diameter, 15 mm radius of curvature) was produced in-house, pressure-field mapped, and calibrated. The transducer was then embedded inside a 1% agar phantom, which was placed under PhS-OCT for observation, under various HIFU power settings (acoustic power, and number of cycles per pulse). Shear wave was induced on the sample surface by HIFU and was captured in full under PhS-OCT. The lowest HIFU acoustic power output for the detection of shear wave was found to be 0.36 W (1.02 MHz, 100 cycles/pulse), or with the number of cycles/pulse as low as 20 (1.02 MHz, 0.98 W acoustic power output). Results:A linear relationship between acoustic power output and the maximum shear wave displacement was found in the first study. The second study explores a non-linear correlation between the (HIFU) numbers of cycles per pulse, and the maximum shear wave displacement. Conclusion:PhS-OCT demonstrates excellent tracking and detection of HIFU-induced shear wave. The results could benefit other imaging techniques in tracking and guiding HIFU focus. Further studies will explore the relationship between the physical transducer characteristics and the HIFU-induced shear wave. [ABSTRACT FROM AUTHOR]

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]