External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Dimension Estimate of Uniform Attractor for a Model of High Intensity Focussed Ultrasound-Induced Thermotherapy.

High intensity focussed ultrasound (HIFU) has emerged as a novel therapeutic modality, for the treatment of various cancers, that is gaining significant traction in clinical oncology. It is a cancer therapy that avoids many of the associated negative side effects of other more well-established therapies (such as surgery, chemotherapy and radiotherapy) and does not lead to the longer recuperation times necessary in these cases. The increasing interest in HIFU from biomedical researchers and clinicians has led to the development of a number of mathematical models to capture the effects of HIFU energy deposition in biological tissue. In this paper, we study the simplest such model that has been utilized by researchers to study temperature evolution under HIFU therapy. Although the model poses significant theoretical challenges, in earlier work, we were able to establish existence and uniqueness of solutions to this system of PDEs (see Efendiev et al. Adv Appl Math Sci 29(1):231-246, 2020). In the current work, we take the next natural step of studying the long-time dynamics of solutions to this model, in the case where the external forcing is quasi-periodic. In this case, we are able to prove the existence of uniform attractors to the corresponding evolutionary processes generated by our model and to estimate the Hausdorff dimension of the attractors, in terms of the physical parameters of the system.

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes.

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Clinical analysis of high-intensity focussed ultrasound ablation for abdominal wall endometriosis: a 4-year experience at a specialty gynecological institution.

OBJECTIVE: To evaluate the long-term clinical effect of high-intensity focussed ultrasound (HIFU) as a non-invasive modality for ablation of abdominal wall endometriosis (AWE) foci. METHODS: All women who were diagnosed with cutaneous endometriosis and underwent HIFU ablation and 4-year follow-up were included. Patient symptoms, imaging performed, HIFU ablation, recurrence, lesion location, size and number were collected and analyzed. RESULTS: A total of 51 women with 57 painful abdominal wall masses with a median volume of 4.00 cm3 and a mean age of 30.5±2.12 years were treated with HIFU. The main symptoms were a palpable painful abdominal mass (93%), protrusion of the skin (28.1%, 16) or lack of protrusion of the skin (71.9%, 41). Ultrasound was initially performed in 100% (51) of women, whereas 6% (3) required MRI examinations to distinguish the features and range of the masses. Ablation was performed with a median 300 s of sonication time, 40 min treatment time, 150 W of power and 41800 J of total energy to treat lesions that were a median volume of 3.83 cm3. No severe complications occurred, except in one patient with a first-degree skin burn, during the 48-month follow-up period. The pooled recurrence of cutaneous endometriosis occurred in 3.9% (2) of women. CONCLUSION: The diagnosis of AWE should be confirmed with imaging of the lesion number, location, size and features before HIFU ablation. HIFU should be the first choice for the treatment of AWE as it is a non-invasive method, with high efficiency and safety and rapid postoperative recovery.

Efficacy and safety of ultrasound-guided high-intensity focused ultrasound for uterine fibroids: a preliminary experience.

The objective of this prospective cohort study was to evaluate the therapeutic efficacy and safety of ultrasound-guided high-intensity focussed ultrasound (HIFU) in the treatment of uterine fibroids. Twenty premenopausal women with symptomatic fibroids underwent ultrasound-guided HIFU therapy. Twenty-two fibroids with a median baseline volume of 127.0 cm3 (range 18.5-481.2 cm3) were treated. The percentages fibroid volume reduction were 46.9 (range -8.8-73.1) at 1-month, 57.4 (-51.5-95.2) at 3-month, 60.1 (-18.9-97.8) at 6-month and 75.9 (-33.7-99.3) at 12-month, after treatment. The modified Uterine Fibroid Symptom and Quality of Life (UFS-QOL) scores were reduced by 40.7% (0-59.3%) at 3-month, 45.5% (0-70.4%) at 6-month and 44.9% (0-71.4%) at 12-month after treatment. Three patients required subsequent surgical interventions. No significant complications were encountered. Ultrasound-guided HIFU appears to be effective and safe for the treatment of symptomatic uterine fibroids in selected patients. Impact statement What is already known on this subject? Ultrasound-guided high-intensity focussed ultrasound (HIFU) is a relatively new uterine-sparing treatment for fibroids. Most clinical reports are from China, which suggest that this treatment is a safe and effective modality. However, in many other countries, HIFU treatment for fibroids, especially using ultrasound as image guidance, is still considered novel with limited clinical experience. What do the results of this study add? This preliminary report adds to our limited local experience on HIFU and provides reassurance on our continual utilisation of this treatment modality for fibroids. With the increasing demand of uterine-sparing alternatives, experiences shared among different countries are important to make this treatment modality generalisable and universally acceptable. What are the implications of these findings for clinical practice and/or further research?Ultrasound-guided HIFU (USgHIFU) can potential be offered as an alternative treatment modality for women with fibroids.

Effect of pre-treatment with gonadotropin-releasing hormone analogue GnRH-α on high-intensity focussed ultrasound ablation for diffuse adenomyosis: a preliminary study.

OBJECTIVES: To evaluate the efficacy and safety of GnRH-α pre-treatment with HIFU ablation for diffuse adenomyosis. METHODS: From January 2014 to December 2016, 61 patients were divided into two groups. Twenty-three patients with larger uteri received pre-treatment with GnRH-α and were then subjected to HIFU, and 38 patients underwent HIFU alone. The technical parameters included treatment time, sonication time, average sonication power, treatment intensity, total energy, non-perfusion volume (NPV) and NPV ratio. Intra-, post-procedural complaints, the relief rate of dysmenorrhoea and clinical effectiveness were followed up. RESULTS: Although the lesion volume in the HIFU + GnRH group was larger than in the HIFU-only group, higher NPV, NPVR%, treatment intensity and total energy with shorter treatment and sonication times in the HIFU + GnRH group were obtained than that in the HIFU-only group. Significant differences were evident for NPV, NPVR%, average power, and total intensity energy (p < 0.05), but not for other parameters between the two groups (p > 0.05). Although no differences in the intra-, post-procedural VAS scores, in the adverse effects and in the relief rate or clinical effectiveness were apparent between the two groups (p > 0.05), the relief rate was better in the HIFU + GnRH group than that in the HIFU group from 6 to 12 months after treatment. Self-comparison of differences occurred in the two groups before and after treatment (p < 0.05) and were between the two groups after only 6 months (p < 0.05). CONCLUSION: The combination of HIFU with GnRH-α is more effective than HIFU alone for ablation of diffuse adenomyosis. Moreover, the GnRH-α pre-treatment with HIFU is safe.

High-intensity focused ultrasound in the treatment of breast fibroadenomata (HIFU-F trial).

BACKGROUND: High-intensity focussed ultrasound (HIFU) is a non-invasive ablative technique utilising the application of high frequency ultrasound (US) pressure waves to cause tissue necrosis. This emerging technology is currently limited by prolonged treatment times. The aim of the HIFU-F trial was to perform circumferential HIFU treatment as a means of shortening treatment times. METHODS: A prospective trial was set up to treat 50 consecutive patients ≥18 years of age. Eligible patients possessed symptomatic fibroadenomata, visible on US. Patients ≥25 years of age required histological confirmation of the diagnosis. Primary outcome measures were reduction in treatment time, reduction in volume on US after 12 months and complication rates. RESULTS: HIFU treatment was performed in 51 patients (53 treatments) with a mean age of 29.8 years (SD 7.2 years) and a diameter of 2.6 cm (SD 1.4 cm). Circumferential ablation reduced treatment times by an estimated 19.9 min (SD 25.1 min), which is a 29.4% (SD 15.2%) reduction compared with whole lesion ablation. Volume reduction of 43.2% (SD 35.4%; p < 0.005, paired t-test) was observed on US at 12 months post-treatment. Local complications completely resolved at 1 month apart from skin hyper-pigmentation, which persisted in nine cases at three months, six cases at 6 months and six at 12 months. CONCLUSION: Circumferential HIFU treatment for breast fibroadenomata is feasible to reduce both lesion size and treatment time. HIFU is a non-invasive alternative technique for the treatment of breast fibroadenomata. ISRCTN registration: 76622747.

Establishment of a scoring system for predicting the difficulty level of high-intensity focussed ultrasound ablation of uterine fibroids.

PURPOSE: To establish a scoring system that predicts the difficulty level of high-intensity focussed ultrasound (HIFU) ablation of uterine fibroids. MATERIALS AND METHODS: Four hundred and twenty-two patients with fibroids were enrolled. The energy efficiency factor (EEF) and sonication time were set as dependent variables, with factors possibly affecting EEF and sonication time including age, body mass index (BMI), the volume of fibroids, the location of the uterus, the type of fibroids, the signal intensity on the T2-weighted imaging (T2WI), the enhancement type, the thickness of the rectus abdominis and the subcutaneous fat layer, the distance from the anterior/posterior surface of the fibroid to the skin, and the abdominal wall scars were set as predictors for building optimal scaling regression models. RESULTS: The volume of the fibroids, the location of the uterus, the signal intensity on T2WI, enhancement type, rectus abdominis thickness, subcutaneous fat thickness, and distance from the anterior surface of fibroid to the skin were related to EEF. Signal intensity on T2WI, the volume of fibroids, distance from the posterior surface of fibroid to the skin, and enhancement type were related to sonication time. Models that can predict the difficulty level of HIFU for fibroids have been established: for EEF, y ' = 0.338X '1 - 0.231X '2+0.156X '3+0.167X '4 ; for sonication time, y = 0.227X1+0.321X2+0.157X3+0.194X4. CONCLUSIONS: A scoring system for predicting the difficulty level of HIFU treatment for uterine fibroids has been established and it can be used to help select patients and to predict the sonication time for a given fibroid.

Magnetic resonance imaging features influencing high-intensity focused ultrasound ablation of adenomyosis with a nonperfused volume ratio of ≥90% as a measure of clinical treatment success: retrospective multivariate analysis.

OBJECTIVE: This retrospective study aimed (1) to investigate the magnetic resonance imaging (MRI) features influencing a nonperfused volume ratio (NPVr) ≥ 90% after high-intensity focussed ultrasound (HIFU) ablation of adenomyosis, and (2) to assess the safety, which was defined in terms of adverse events (AEs) and changes in anti-Mullerian hormone (AMH) concentrations, and clinical efficacy, which was defined in terms of adenomyosis volume reduction and symptom improvement at 6 months' follow-up. METHODS: Sixty-six women who underwent HIFU treatment were divided into groups A (NPVr ≥90%; n = 26) and B (NPVr <90%, n = 40). Multivariate logistic regression analyses of MRI features were conducted to identify the potential predictors of an NPVr ≥90%. RESULTS: Generalized estimating equation (GEE) analysis was used to model the prediction of an NPVr ≥90% with four significant predictors from multivariate analyses: the thickness of the subcutaneous fat layer, adenomyosis volume, T2 signal intensity (SI) ratio of adenomyosis to myometrium, and the Ktrans ratio of adenomyosis to myometrium. Clinical efficacy was significantly greater in group A than in group B. The findings showed no serious AEs and no significant differences between AMH concentrations before and 6 months after treatment. CONCLUSIONS: The present retrospective study demonstrated that achievement of NPVr ≥90% as a measure of clinical treatment success in MRI-guided HIFU treatment of adenomyosis using multivariate analyses and a prediction model is clinically possible without compromising the safety of patients.

Thermal diffusivity and perfusion constants from in vivo MR-guided focussed ultrasound treatments: a feasibility study.

PURPOSE: This study investigates the feasibility of non-invasively determining thermal diffusivity (α) and the Pennes perfusion parameter (w) from pre-clinical and clinical magnetic resonance-guided focussed ultrasound (MRgFUS) temperature data. MATERIALS AND METHODS: Pre-clinical MRgFUS experiments were performed in rabbit muscle (N = 3, 28 sonications) using three-dimensional MR thermometry. Eight sonications were made in a clinical QA phantom with two-dimensional thermometry. Retrospective property determination was performed on clinical uterine fibroid (N = 8, 9 sonications) and desmoid tumour (N = 4, 7 sonications) data. The property determination method fits an analytical solution to MRgFUS temperatures in the coronal MR plane, including all temperatures acquired during heating and one cooling image. When possible, additional cooling data were acquired for property determination. RESULTS: Rabbit α and w from Heating Data (α = 0.164 mm2s-1, w = 7.9 kg m-3 s-1) and Heating and Cooling Data (α = 0.146 mm2s-1, w = 3.3 kg m-3 s-1) were within the range of gold-standard invasive measurements, with >50% reduction in variability by including cooling data. QA phantom property determination with cooling data yielded properties within 3% of expected values (α = 0.144 mm2s-1, w = 0.0 kg m-3 s-1), a difference that was not statistically significant (p = 0.053). Uterine fibroid (Heating Data: α = 0.212 mm2s-1, w = 11.0 kg m-3 s-1) and desmoid tumour (Heating & Cooling Data: α = 0.245 mm2s-1, w = 4.7 kg m-3 s-1) properties are feasible but lack independent verification. CONCLUSIONS: Thermal diffusivity and the Pennes perfusion parameter can be obtained from in vivo data and with clinical MRgFUS protocols. Property values are consistently improved by including cooling data. The utility of this property determination method will increase as clinical protocols implement improved temperature imaging.

A retrospective study of ultrasound-guided high intensity focussed ultrasound ablation for multiple uterine fibroids in South Africa.

OBJECTIVE: To evaluate the shrinkage rate, symptom relief and improvement of the quality of life following ultrasound-guided high intensity focussed ultrasound (USgHIFU) for multiple uterine fibroids. METHODS: From October 2015 to November 2016, 81 black women with multiple symptomatic fibroids underwent USgHIFU. The number of the fibroids ranged from 3 to 9. The shrinkage rate of fibroids, symptom severity score and quality of life were evaluated following USgHIFU. Magnetic resonance imaging (MRI), the uterine fibroid symptom and quality of life (UFS-QOL) questionnaire were used for evaluation. RESULTS: The mean age of patients was 35.3 ± 5.9 years. The average weight of these patients was 68.4 ± 11.4 kg, with the median abdominal subcutaneous fat thickness of 38.0 ± 11.4 mm. The median fibroid volume was 36.0 (range: 1.8-1220.1) cm³. During HIFU, 60.5% of the patients reported lower abdominal pain, 43.2% sciatic/buttock pain, 60.5% skin "burning" sensation, 6.2% abnormal vaginal discharge and 13.6% transient leg pain. No severe complications were observed. The average volume reduction rate of fibroids in 21 patients who completed the follow-up was 32.5 ± 24.0, 42.3 ± 32.2 and 52.5 ± 36.3% 1, 3 and 6 months after HIFU, respectively. The UFS score decreased and the QOL values significantly increased during the follow-up period. Re-intervention treatment occurred in two of the 21 patients 6 months after HIFU. One patient conceived 3 months after HIFU, and she had a term vaginal delivery without any obstetrical complications. CONCLUSIONS: Based on our results, USgHIFU is safe and effective in treating patients with multiple uterine fibroids.

Experimental assessment of phase aberration correction for breast MRgFUS therapy.

PURPOSE: This study validates that phase aberrations in breast magnetic resonance-guided focussed ultrasound (MRgFUS) therapies can be corrected in a clinically relevant time frame to generate more intense, smaller and more spatially accurate foci. MATERIALS AND METHODS: Hybrid angular spectrum (HAS) ultrasound calculations in an magnetic resonance imaging (MRI)-based tissue model, were used to compute phase aberration corrections for improved experimental MRgFUS heating in four heterogeneous breast-mimicking phantoms (n = 18 total locations). Magnetic resonance(MR) temperature imaging was used to evaluate the maximum temperature rise, focus volume and focus accuracy for uncorrected and phase aberration-corrected sonications. Thermal simulations assessed the effectiveness of the phase aberration correction implementation. RESULTS: In 13 of 18 locations, the maximum temperature rise increased by an average of 30%, focus volume was reduced by 40% and focus accuracy improved from 4.6 to 3.6 mm. Mixed results were observed in five of the 18 locations, with focus accuracy improving from 6.1 to 2.5 mm and the maximum temperature rise decreasing by 8% and focus volume increasing by 10%. Overall, the study demonstrated significant improvements (p < 0.005) in maximum temperature rise, focus volume and focus accuracy. Simulations predicted greater improvements than observed experimentally, suggesting potential for improvement in implementing the technique. The complete phase aberration correction procedure, including model generation, segmentation and phase aberration computations, required less than 45 min per sonication location. CONCLUSION: The significant improvements demonstrated in this study i.e., focus intensity, size and accuracy from phase aberration correction have the potential to improve the efficacy, time-efficiency and safety of breast MRgFUS therapies.

Factors influencing thermal injury to skin and abdominal wall structures in HIFU ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal wall structures in ultrasound-guided high-intensity focussed ultrasound (USgHIFU) ablation of uterine fibroids. METHOD: A total of 892 patients with uterine fibroids diagnosed on contrast-enhanced magnetic resonance imaging (MRI) scans received HIFU ablation and follow-up MRI scanning. After therapy, thermal injury to the skin was assessed via measurement of skin redness, blisters, subcutaneous nodules and to the abdominal wall structures via measurement of signal intensity on T2-weighted MRI images. A total of 151 patients were assigned to the injury group, 741 patients were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were analysed using univariate and multiple logistic regression analyses. RESULTS: Univariate logistic regression revealed that sonication time, sonication time per hour, total energy deposited, distance from uterine fibroid ventral side to skin, volume of uterine fibroids, abdominal wall scar, abdominal wall thickness and body mass index (BMI) all affected whether thermal injury occurred (p < 0.05). Subsequently, multiple logistic regression analysis revealed that total energy (p = 0.000, OR = 2.228, 95% CI 1.831-2.712), abdominal wall scar (p = 0.019, OR = 1.639, 95% CI 1.085-2.477) and abdominal wall thickness (p = 0.000, OR = 1.562, 95% CI 1.313-1.857) were significantly correlated with thermal injury. CONCLUSION: Multiple logistic regression analysis revealed that abdominal wall thickness, total energy and abdominal wall scar were the most significant influencing factors that influenced minimal thermal injury of abdominal wall structures in USgHIFU ablation of uterine fibroids.

Mechanical fractionation of tissues using microsecond-long HIFU pulses on a clinical MR-HIFU system.

PURPOSE: High intensity focussed ultrasound (HIFU) can non-invasively treat tumours with minimal or no damage to intervening tissues. While continuous-wave HIFU thermally ablates target tissue, the effect of hundreds of microsecond-long pulsed sonications is examined in this work. The objective of this study was to characterise sonication parameter-dependent thermomechanical bioeffects to provide the foundation for future preclinical studies and facilitate clinical translation. METHODS AND MATERIALS: Acoustic power, number of cycles/pulse, sonication time and pulse repetition frequency (PRF) were varied on a clinical magnetic resonance imaging (MRI)-guided HIFU (MR-HIFU) system. Ex vivo porcine liver, kidney and cardiac muscle tissue samples were sonicated (3 × 3 grid pattern, 1 mm spacing). Temperature, thermal dose and T2 relaxation times were quantified using MRI. Lesions were histologically analysed using H&E and vimentin stains for lesion structure and viability. RESULTS: Thermomechanical HIFU bioeffects produced distinct types of fractionated tissue lesions: solid/thermal, paste-like and vacuolated. Sonications at 20 or 60 Hz PRF generated substantial tissue damage beyond the focal region, with reduced viability on vimentin staining, whereas H&E staining indicated intact tissue. Same sonication parameters produced dissimilar lesions in different tissue types, while significant differences in temperature, thermal dose and T2 were observed between the parameter sets. CONCLUSION: Clinical MR-HIFU system was utilised to generate distinct types of lesions and to produce targeted thermomechanical bioeffects in ex vivo tissues. The results guide HIFU research on thermomechanical tissue bioeffects, inform future studies and advice sonication parameter selection for direct tumour ablation or immunomodulation using a clinical MR-HIFU system.

Numerical evaluation of the effect of electronically steering a phased array transducer: axially post-focal shifting.

PURPOSE: HIFU has been emerging as an effective and safe modality for the treatment of solid tumours and cancers. The focus shifting range of phased array HIFU transducer is an important safety concern because of the presence of grating lobe in the pre-focal region. However, previous studies were only based on linear acoustic wave model. MATERIALS AND METHODS: The nonlinear wave propagation from a 256-element phased array through multiple layered media was simulated using the angular spectrum approach (ASA) in marching fractional steps with the consideration of diffraction, attenuation and non-linearity effects by a second-order operator splitting scheme. The distribution of acoustic intensities, temperature elevations, lesion sizes and grating lobe levels were calculated at various axially post-focal shifting distances and driving frequencies. RESULTS: Axially shifting HIFU focus leads to significant increase of the acoustic intensity at the grating lobe, but decrease at the main lobe. The influences on the acoustic field, thermal field and lesion sizes are determined by the shifting distance and driving frequency, and variations can be fit monotonically and linearly. Prediction accuracies by simple regression models are satisfactory. Irreversible tissue coagulation could be generated by the grating lobe at certain conditions. CONCLUSIONS: The established nonlinear wave propagation algorithm allows the accurate description of HIFU field and consequently the evaluation of grating lobe and steerability of focus. The influence of focus shifting may be predicted simply. The treatment planning of phased array HIFU ablation could be optimised by setting the appropriate exposure and focus scanning schemes.

Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis.

PURPOSE: Breast-conserving surgery is effective for breast cancer treatment but is associated with morbidity in particular high re-excision rates. We performed a systematic review and meta-analysis to assess the current evidence for clinical outcomes with minimally invasive ablative techniques in the non-surgical treatment of breast cancer. METHODS: A systematic search of the literature was performed using PubMed and Medline library databases to identify all studies published between 1994 and May 2016. Studies were considered eligible for inclusion if they evaluated the role of ablative techniques in the treatment of breast cancer and included ten patients or more. Studies that failed to fulfil the inclusion criteria were excluded. RESULTS: We identified 63 studies including 1608 patients whose breast tumours were treated with radiofrequency (RFA), high intensity focussed ultrasound (HIFU), cryo-, laser or microwave ablation. Fifty studies reported on the number of patients with complete ablation as found on histopathology and the highest rate of complete ablation was achieved with RFA (87.1%, 491/564) and microwave ablation (83.2%, 89/107). Short-term complications were most often reported with microwave ablation (14.6%, 21/144). Recurrence was reported in 24 patients (4.2%, 24/570) and most often with laser ablation (10.7%, 11/103). The shortest treatment times were observed with RFA (15.6 ± 5.6 min) and the longest with HIFU (101.5 ± 46.6 min). CONCLUSION: Minimally invasive ablative techniques are able to successfully induce coagulative necrosis in breast cancer with a low side effect profile. Adequately powered and prospectively conducted cohort trials are required to confirm complete pathological ablation in all patients.

Magnetic resonance texture parameters are associated with ablation efficiency in MR-guided high-intensity focussed ultrasound treatment of uterine fibroids.

OBJECTIVES: The objective of this study is to assess the association between texture parameter analysis derived from T2-weighted images and efficiency of magnetic resonance-guided focussed ultrasound (MRgFUS) ablation for the treatment of uterine fibroids. MATERIALS AND METHODS: Fifty-five women treated by MRgFUS were included in this retrospective analysis. Texture parameters were calculated using three 2D regions of interest placed on three consecutive slices on the same sagittal 3D T2-weighted images obtained at the beginning of MRgFUS ablation. Using uni- and multi-variate linear regression, texture parameters, fibroids/muscular T2W ratio (T2Wr), Funaki type, and fibroid depth were correlated with ablation efficiency, defined as the ratio of non-perfused volume (NPV) on post-treatment contrast-enhanced MRI by total volume of treatment-cell sizes used. Inter-rater reproducibility for texture analysis was assessed using variation coefficients. RESULTS: The mean total treatment cell volume was 49.5 (±30) ml, corresponding to a mean NPV of 57.2 (±57) ml (28%). The mean ablation efficiency was 1.14 (±0.7), with a range of 0.03-3.6. In addition to fibroid/muscular T2Wr, seven of the 14 texture parameters were significantly correlated with ablation efficiency: mean signal intensity (p = .047); Skewness (p = .03); Kurtosis (p = .015); mean uniformity (p = .052); mean sum of square (p = .045); mean sum entropy (p = .021) and mean entropy (p = .051). In multivariate linear regression, fibroid/muscular T2Wr and sum of entropy were associated with ablation efficiency. The inter-rater coefficient of variation for sum entropy was 2.6%. CONCLUSIONS: Uterine fibroid texture parameters provide complementary information to T2Wr, and are associated with MRgFUS efficiency. Key points Mean sum entropy is negatively correlated with MRgFUS efficiency (ρ = -0.307, p = .021). Fibroids/muscular T2-weighted ratio and entropy are associated with MRgFUS efficiency. Texture parameters are better predictors of MRgFUS efficiency than Funaki type. Fibroid MR texture analysis can improve patient selection for MRgFUS.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Tissue specific considerations in implementing high intensity focussed ultrasound under magnetic resonance imaging guidance.

High-intensity focused ultrasound can ablate a target permanently, leaving tissues through which it passes thermally unaffected. When delivered under magnetic resonance (MR) imaging guidance, the change in tissue relaxivity on heating is used to monitor the temperatures achieved. Different tissue types in the pre-focal beam path result in energy loss defined by their individual attenuation coefficients. Furthermore, at interfaces with different acoustic impedances the beam will be both reflected and refracted, changing the position of the focus. For complex interfaces this effect is exacerbated. Moreover, blood vessels proximal to the focal region can dissipate heat, altering the expected region of damage. In the target volume, the temperature distribution depends on the thermal conductivity (or diffusivity) of the tissue and its heat capacity. These are different for vascular tissues, water and fat containing tissues and bone. Therefore, documenting the characteristics of the pre-focal and target tissues is critical for effective delivery of HIFU. MR imaging provides excellent anatomic detail and characterization of soft tissue components. It is an ideal modality for real-time planning and monitoring of HIFU ablation, and provides non-invasive temperature maps. Clinical applications involve soft-tissue (abdomino-pelvic applications) or bone (brain applications) pre-focally and at the target (soft-tissue tumors and bone metastases respectively). This article addresses the technical difficulties of delivering HIFU effectively when vascular tissues, densely cellular tissues, fat or bone are traversed pre-focally, and the clinical applications that target these tissues. The strengths and limitations of MR techniques used for monitoring ablation in these tissues are also discussed.

Acardius acephalus with spontaneous umbilical cord occlusion: Reporting a rare case.

Twin reversed arterial perfusion syndrome is a rare obstetric condition that occurs in monochorionic twin pregnancies, resulting in coexistence of a normal "pump" twin and an acardiac twin. The acardiac twin is dependent upon the normal twin to provide circulation by means of vascular anastomosis, thereby putting the pump fetus at risk of high output cardiac failure. Overall only 50% of pump twins survive. Mortality for acardiac twin is 100%. We present a case of 26-year-old primigravida female presenting with 8 months of amenorrhea with unsure LMP. Ultrasonography followed by fetal MRI was carried out which revealed acardius acephalus twin with absence of blood flow in umbilical vessels. Pump twin had multicystic dysplastic left kidney with single umbilical artery. Following delivery, the pump twin survived well and the deformed fetus showed features of twin reversed arterial perfusion syndrome.