Development and validation of a deep learning-based method for automatic measurement of uterus, fibroid, and ablated volume in MRI after MR-HIFU treatment of uterine fibroids.

INTRODUCTION: The non-perfused volume divided by total fibroid load (NPV/TFL) is a predictive outcome parameter for MRI-guided high-intensity focused ultrasound (MR-HIFU) treatments of uterine fibroids, which is related to long-term symptom relief. In current clinical practice, the MR-HIFU outcome parameters are typically determined by visual inspection, so an automated computer-aided method could facilitate objective outcome quantification. The objective of this study was to develop and evaluate a deep learning-based segmentation algorithm for volume measurements of the uterus, uterine fibroids, and NPVs in MRI in order to automatically quantify the NPV/TFL. MATERIALS AND METHODS: A segmentation pipeline was developed and evaluated using expert manual segmentations of MRI scans of 115 uterine fibroid patients, screened for and/or undergoing MR-HIFU treatment. The pipeline contained three separate neural networks, one per target structure. The first step in the pipeline was uterus segmentation from contrast-enhanced (CE)-T1w scans. This segmentation was subsequently used to remove non-uterus background tissue for NPV and fibroid segmentation. In the following step, NPVs were segmented from uterus-only CE-T1w scans. Finally, fibroids were segmented from uterus-only T2w scans. The segmentations were used to calculate the volume for each structure. Reliability and agreement between manual and automatic segmentations, volumes, and NPV/TFLs were assessed. RESULTS: For treatment scans, the Dice similarity coefficients (DSC) between the manually and automatically obtained segmentations were 0.90 (uterus), 0.84 (NPV) and 0.74 (fibroid). Intraclass correlation coefficients (ICC) were 1.00 [0.99, 1.00] (uterus), 0.99 [0.98, 1.00] (NPV) and 0.98 [0.95, 0.99] (fibroid) between manually and automatically derived volumes. For manually and automatically derived NPV/TFLs, the mean difference was 5% [-41%, 51%] (ICC: 0.66 [0.32, 0.85]). CONCLUSION: The algorithm presented in this study automatically calculates uterus volume, fibroid load, and NPVs, which could lead to more objective outcome quantification after MR-HIFU treatments of uterine fibroids in comparison to visual inspection. When robustness has been ascertained in a future study, this tool may eventually be employed in clinical practice to automatically measure the NPV/TFL after MR-HIFU procedures of uterine fibroids.

Intravoxel incoherent motion (IVIM)-derived perfusion fraction mapping for the visual evaluation of MR-guided high intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids.

BACKGROUND: A method for periprocedural contrast agent-free visualization of uterine fibroid perfusion could potentially shorten magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment times and improve outcomes. Our goal was to test feasibility of perfusion fraction mapping by intravoxel incoherent motion (IVIM) modeling using diffusion-weighted MRI as method for visual evaluation of MR-HIFU treatment progression. METHODS: Conventional and T2-corrected IVIM-derived perfusion fraction maps were retrospectively calculated by applying two fitting methods to diffusion-weighted MRI data (b = 0, 50, 100, 200, 400, 600 and 800 s/mm2 at 1.5 T) from forty-four premenopausal women who underwent MR-HIFU ablation treatment of uterine fibroids. Contrast in perfusion fraction maps between areas with low perfusion fraction and surrounding tissue in the target uterine fibroid immediately following MR-HIFU treatment was evaluated. Additionally, the Dice similarity coefficient (DSC) was calculated between delineated areas with low IVIM-derived perfusion fraction and hypoperfusion based on CE-T1w. RESULTS: Average perfusion fraction ranged between 0.068 and 0.083 in areas with low perfusion fraction based on visual assessment, and between 0.256 and 0.335 in surrounding tissues (all p < 0.001). DSCs ranged from 0.714 to 0.734 between areas with low perfusion fraction and the CE-T1w derived non-perfused areas, with excellent intraobserver reliability of the delineated areas (ICC 0.97). CONCLUSION: The MR-HIFU treatment effect in uterine fibroids can be visualized using IVIM perfusion fraction mapping, in moderate concordance with contrast enhanced MRI. IVIM perfusion fraction mapping has therefore the potential to serve as a contrast agent-free imaging method to visualize the MR-HIFU treatment progression in uterine fibroids.

Effectiveness and complication rates of high intensity focused ultrasound treatment for abdominal wall endometriosis: A systematic review.

In this review, a systematic literature search on the effectiveness and complication rates of ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USg-/MRgHIFU) for abdominal wall endometriosis (AWE) was conducted in six databases in May/June 2023. Original articles of (non)randomized trials, cohort studies, case-control studies and case series published in peer-reviewed journals were included. Of the included studies the level of evidence (LoE) and methodological quality using the ROBINS-I and IHE-QAT was assessed. Primary outcomes were non-perfused volume ratio (NPV%), lesion size, pain scores, side effects and complication rates according to Society of Interventional Radiology (SIR) guidelines. Secondary outcomes were recurrence and re-intervention rates. Seven cohort studies (one of good methodological quality) (LoE 3) on USgHIFU were included (n = 212, AWE lesions = 240-245). Six months after USgHIFU treatment, pain scores were reduced with 3.3-5.2 points (baseline: 5.1-6.8, n = 135). Self-limiting side effects were pain (85.7 % (114/133)) and swelling (34.6 % (46/133)) in the treatment area. Complications occurred in 17.7 % (32/181), all of which were minor. Recurrence occurred in 12.8 % (11/86). Three of these seven cohort studies compared USgHIFU (n = 61) with surgical excision (n = 74). Pooled results showed no significant differences in pain scores, complications (resp. 26.3 % (10/38) vs. 32.6 % (15/46) (p = 0.53)) and recurrences (resp. 4.9 % (3/61) vs. 5.4 % (4/74) (p = 0.90)). This systematic review suggests that HIFU is an effective and safe treatment option for AWE. USgHIFU treatment led to reduced pain scores and lesion size, was free of major complications and had a pooled recurrence rate of 12.8 %. Compared to surgical excision pooled results showed no significant differences in pain scores, complications and recurrences after USgHIFU. However, many of the included studies had limitations in their methodological quality and therefore the results should be interpreted with caution. Well-structured high-quality randomized controlled trials comparing HIFU to standard care should be conducted to provide more conclusive evidence.

Waste analysis and energy use estimation during MR-HIFU treatment: first steps towards calculating total environmental impact.

OBJECTIVES: To assess the environmental impact of the non-invasive Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, we aimed to perform a full Life Cycle Assessment (LCA). However, as a full LCA was not feasible at this time, we evaluated the CO2 (carbon dioxide) emission from the MRI scanner, MR-HIFU device, and the medication used, and analyzed solid waste produced during treatment. METHODS: Our functional unit was one uterine fibroid MR-HIFU treatment. The moment the patient entered the day care-unit until she left, defined our boundaries of investigation. We retrospectively collected data from 25 treatments to assess the CO2 emission based on the energy used by the MRI scanner and MR-HIFU device and the amount and type of medication administered. Solid waste was prospectively collected from five treatments. RESULTS: During an MR-HIFU treatment, the MRI scanner and MR-HIFU device produced 33.2 ± 8.7 kg of CO2 emission and medication administered 0.13 ± 0.04 kg. A uterine fibroid MR-HIFU treatment produced 1.2 kg (range 1.1-1.4) of solid waste. CONCLUSIONS: Environmental impact should ideally be analyzed for all (new) medical treatments. By assessing part of the CO2 emission and solid waste produced, we have taken the first steps towards analyzing the total environmental impact of the MR-HIFU treatment of uterine fibroids. These data can contribute to future studies comparing the results of MR-HIFU LCAs with LCAs of other uterine fibroid therapies. CRITICAL RELEVANCE STATEMENT: In addition to (cost-) effectiveness, the environmental impact of new treatments should be assessed. We took the first steps towards analyzing the total environmental impact of uterine fibroid MR-HIFU. KEY POINTS: • Life Cycle Assessments (LCAs) should be performed for all (new) medical treatments. • We took the first steps towards analyzing the environmental impact of uterine fibroid MR-HIFU. • Energy used by the MRI scanner and MR-HIFU device corresponded to 33.2 ± 8.7 kg of CO2 emission.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88-1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73-2.38; p = 0.44). Grade 3-4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed.

No Difference in Revision Rates and High Survival Rates in Large-head Metal-on-metal THA Versus Metal-on-polyethylene THA: Long-term Results of a Randomized Controlled Trial.

BACKGROUND: Pseudotumor formation is a well-known complication in metal-on-metal (MoM) THA. Pseudotumors combined with elevated serum ion levels and complaints from patients can lead to high revision rates. Long-term (> 10 years) results obtained from randomized trials comparing large-head MoM THA and conventional metal-on-polyethylene (MoP) THA are lacking regarding revision and survival rates, pseudotumor formation, functional outcomes, and serum ion levels. QUESTIONS/PURPOSES: At 10 years of follow-up, (1) what is the difference in survival and revision rates between large-head (38 to 60 mm) MoM THA and conventional 28-mm MoP THA? (2) What is the difference in pseudotumor formation between large-head MoM THA and MoP THA? (3) Is there a difference in functional outcome between large-head MoM THA and MoP THA? (4) What is the difference in serum ion levels between large-head MoM THA and MoP THA? METHODS: Between January 2006 and December 2008, 104 patients were randomized to receive either cementless MoM THA (50 patients) or cementless MoP THA (54 patients). In all, 78% (81 of 104) of patients completed the 10-year postoperative follow-up: 36 patients with MoM THA (72%; six patients lost to follow-up) and 45 with MoP THA (83%; four lost to follow-up). In the MoM group, 47% (17) were men, and the patients had a mean ± SD age of 60 ± 5 years. In the MoP group, 38% (17) were men, and the patients had a mean age of 61 ± 5 years. All baseline characteristics were similar between the groups. At 10 years of follow-up, all patient records were screened for revision surgery or complications, and the primary endpoint was survivorship free from revision for any cause at the 10-year follow-up interval, which we analyzed using a Kaplan-Meier survival analysis. All patients had a CT scan to determine the pseudotumor classification, which was reviewed by an independent radiologist. Functional outcome was measured using the patient-reported Oxford Hip Score and Harris Hip Score; the latter was assessed by a blinded nurse practitioner. Finally, serum ion cobalt and chrome concentrations were measured at 10 years postoperatively. Because the a priori sample size calculation for this randomized controlled trial was based on a different endpoint, a post hoc power analysis was performed for this long-term follow-up study, with survival as the primary outcome. It showed that considering the number of included patients, this study would have sufficient power (one-sided testing, alpha 0.05, power 80%) to discern a difference of 20% in the survival rate between the MoP and MoM groups (95% versus 75%). RESULTS: With the numbers available, there was no difference in survivorship free from revision for any cause between the MoP group and MoM group at 10 years (95% [95% CI 85% to 98%] versus 92% [95% CI 82% to 98%]; p = 0.6). A higher percentage of patients in the MoM group had pseudotumors on CT than those in the MoP group did, but pseudotumors were observed in both groups (56% [20 of 36] in the MoM group versus 22% [10 of 45] in the MoP group, relative risk 1.8 [95% CI 1.2 to 2.6]; p = 0.002). A higher proportion of elevated cobalt and chrome levels was found in the MoM group (19% and 14%, respectively) than in the MoP group (0% for both cobalt and chrome) (cobalt: RR 1.2 [95% CI 1.1 to 1.5]; p = 0.002; chrome: RR 1.2 [95% CI 1.0 to 1.3]; p = 0.01). In 25% of the patients with pseudotumors (5 of 20 patients), there were elevated serum cobalt levels. None of the 23 patients without pseudotumors had elevated cobalt levels (RR 1.3 [95% CI 1.0 to 1.7]; p = 0.01). There was no difference in functional outcome between study groups, nor a difference between patients with a pseudotumor and those without. CONCLUSION: This study showed that the survival of patients with large-head MoM THA was high and comparable to that of those with MoP THA, which contrasts with the high revision rates reported by others. Although some patients with MoP THAs experienced pseudotumors, the risk of a pseudotumor was much greater in MoM hips, and serum ion levels were higher in patients who received an MoM THA. For these reasons and unknown future complications, continued surveillance of patients with MoM THAs seems important. LEVEL OF EVIDENCE: Level I, therapeutic study.

Is AI the way forward for reducing metal artifacts in CT? Development of a generic deep learning-based method and initial evaluation in patients with sacroiliac joint implants.

PURPOSE: To develop a deep learning-based metal artifact reduction technique (dl-MAR) and quantitatively compare metal artifacts on dl-MAR-corrected CT-images, orthopedic metal artifact reduction (O-MAR)-corrected CT-images and uncorrected CT-images after sacroiliac (SI) joint fusion. METHODS: dl-MAR was trained on CT-images with simulated metal artifacts. Pre-surgery CT-images and uncorrected, O-MAR-corrected and dl-MAR-corrected post-surgery CT-images of twenty-five patients undergoing SI joint fusion were retrospectively obtained. Image registration was applied to align pre-surgery with post-surgery CT-images within each patient, allowing placement of regions of interest (ROIs) on the same anatomical locations. Six ROIs were placed on the metal implant and the contralateral side in bone lateral of the SI joint, the gluteus medius muscle and the iliacus muscle. Metal artifacts were quantified as the difference in Hounsfield units (HU) between pre- and post-surgery CT-values within the ROIs on the uncorrected, O-MAR-corrected and dl-MAR-corrected images. Noise was quantified as standard deviation in HU within the ROIs. Metal artifacts and noise in the post-surgery CT-images were compared using linear multilevel regression models. RESULTS: Metal artifacts were significantly reduced by O-MAR and dl-MAR in bone (p < 0.001), contralateral bone (O-MAR: p = 0.009; dl-MAR: p < 0.001), gluteus medius (p < 0.001), contralateral gluteus medius (p < 0.001), iliacus (p < 0.001) and contralateral iliacus (O-MAR: p = 0.024; dl-MAR: p < 0.001) compared to uncorrected images. Images corrected with dl-MAR resulted in stronger artifact reduction than images corrected with O-MAR in contralateral bone (p < 0.001), gluteus medius (p = 0.006), contralateral gluteus medius (p < 0.001), iliacus (p = 0.017), and contralateral iliacus (p < 0.001). Noise was reduced by O-MAR in bone (p = 0.009) and gluteus medius (p < 0.001) while noise was reduced by dl-MAR in all ROIs (p < 0.001) in comparison to uncorrected images. CONCLUSION: dl-MAR showed superior metal artifact reduction compared to O-MAR in CT-images with SI joint fusion implants.

CT radiomics compared to a clinical model for predicting checkpoint inhibitor treatment outcomes in patients with advanced melanoma.

INTRODUCTION: Predicting checkpoint inhibitors treatment outcomes in melanoma is a relevant task, due to the unpredictable and potentially fatal toxicity and high costs for society. However, accurate biomarkers for treatment outcomes are lacking. Radiomics are a technique to quantitatively capture tumour characteristics on readily available computed tomography (CT) imaging. The purpose of this study was to investigate the added value of radiomics for predicting clinical benefit from checkpoint inhibitors in melanoma in a large, multicenter cohort. METHODS: Patients who received first-line anti-PD1±anti-CTLA4 treatment for advanced cutaneous melanoma were retrospectively identified from nine participating hospitals. For every patient, up to five representative lesions were segmented on baseline CT, and radiomics features were extracted. A machine learning pipeline was trained on the radiomics features to predict clinical benefit, defined as stable disease for more than 6 months or response per RECIST 1.1 criteria. This approach was evaluated using a leave-one-centre-out cross validation and compared to a model based on previously discovered clinical predictors. Lastly, a combination model was built on the radiomics and clinical model. RESULTS: A total of 620 patients were included, of which 59.2% experienced clinical benefit. The radiomics model achieved an area under the receiver operator characteristic curve (AUROC) of 0.607 [95% CI, 0.562-0.652], lower than that of the clinical model (AUROC=0.646 [95% CI, 0.600-0.692]). The combination model yielded no improvement over the clinical model in terms of discrimination (AUROC=0.636 [95% CI, 0.592-0.680]) or calibration. The output of the radiomics model was significantly correlated with three out of five input variables of the clinical model (p < 0.001). DISCUSSION: The radiomics model achieved a moderate predictive value of clinical benefit, which was statistically significant. However, a radiomics approach was unable to add value to a simpler clinical model, most likely due to the overlap in predictive information learned by both models. Future research should focus on the application of deep learning, spectral CT-derived radiomics, and a multimodal approach for accurately predicting benefit to checkpoint inhibitor treatment in advanced melanoma.

Factors Influencing the Adoption of Magnetic Resonance-Guided High-Intensity Focused Ultrasound for Painful Bone Metastases in Europe, A Group Concept Mapping Study.

Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) is an innovative treatment for patients with painful bone metastases. The adoption of MR-HIFU will be influenced by several factors beyond its effectiveness. To identify contextual factors affecting the adoption of MR-HIFU, we conducted a group concept mapping (GCM) study in four European countries. The GCM was conducted in two phases. First, the participants brainstormed statements guided by the focus prompt "One factor that may influence the uptake of MR-HIFU in clinical practice is...". Second, the participants sorted statements into categories and rated the statements according to their importance and changeability. To generate a concept map, multidimensional scaling and cluster analysis were conducted, and average ratings for each (cluster of) factors were calculated. Forty-five participants contributed to phase I and/or II (56% overall participation rate). The resulting concept map comprises 49 factors, organized in 12 clusters: "competitive treatments", "physicians' attitudes", "alignment of resources", "logistics and workflow", "technical disadvantages", "radiotherapy as first-line therapy", "aggregating knowledge and improving awareness", "clinical effectiveness", "patients' preferences", "reimbursement", "cost-effectiveness" and "hospital costs". The factors identified echo those from the literature, but their relevance and interrelationship are case-specific. Besides evidence on clinical effectiveness, contextual factors from 10 other clusters should be addressed to support adoption of MR-HIFU.

Diffusion-weighted MRI with deep learning for visualizing treatment results of MR-guided HIFU ablation of uterine fibroids.

OBJECTIVES: No method is available to determine the non-perfused volume (NPV) repeatedly during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablations of uterine fibroids, as repeated acquisition of contrast-enhanced T1-weighted (CE-T1w) scans is inhibited by safety concerns. The objective of this study was to develop and test a deep learning-based method for translation of diffusion-weighted imaging (DWI) into synthetic CE-T1w scans, for monitoring MR-HIFU treatment progression. METHODS: The algorithm was retrospectively trained and validated on data from 33 and 20 patients respectively who underwent an MR-HIFU treatment of uterine fibroids between June 2017 and January 2019. Postablation synthetic CE-T1w images were generated by a deep learning network trained on paired DWI and reference CE-T1w scans acquired during the treatment procedure. Quantitative analysis included calculation of the Dice coefficient of NPVs delineated on synthetic and reference CE-T1w scans. Four MR-HIFU radiologists assessed the outcome of MR-HIFU treatments and NPV ratio based on the synthetic and reference CE-T1w scans. RESULTS: Dice coefficient of NPVs was 71% (± 22%). The mean difference in NPV ratio was 1.4% (± 22%) and not statistically significant (p = 0.79). Absolute agreement of the radiologists on technical treatment success on synthetic and reference CE-T1w scans was 83%. NPV ratio estimations on synthetic and reference CE-T1w scans were not significantly different (p = 0.27). CONCLUSIONS: Deep learning-based synthetic CE-T1w scans derived from intraprocedural DWI allow gadolinium-free visualization of the predicted NPV, and can potentially be used for repeated gadolinium-free monitoring of treatment progression during MR-HIFU therapy for uterine fibroids. KEY POINTS: • Synthetic CE-T1w scans can be derived from diffusion-weighted imaging using deep learning. • Synthetic CE-T1w scans may be used for visualization of the NPV without using a contrast agent directly after MR-HIFU ablations of uterine fibroids.

Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial.

BACKGROUND: Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. METHODS/DESIGN: The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. DISCUSSION: The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU-alone or in combination with EBRT-compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. TRIAL REGISTRATION: The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13-01-2020.

Magnetic Resonance Imaging-targeted Prostate Biopsy Compared with Systematic Prostate Biopsy in Biopsy-naïve Patients with Suspected Prostate Cancer.

Background: It remains uncertain whether transrectal ultrasound (TRUS)-guided systematic biopsies can be omitted and rely solely on multiparametric magnetic resonance imaging-targeted biopsies (MRI-TBx) in biopsy-naïve men suspected of prostate cancer (PCa). Objective: To compare PCa detection in biopsy-naïve men between systematic biopsy and MRI-TBx. Design setting and participants: A prospective cohort study was conducted in a Dutch teaching hospital. Consecutive patients with suspected PCa, no history of biopsy, and no clinical suspicion of metastasis underwent both TRUS-guided systematic biopsies and MRI-TBx by multiparametric magnetic resonance imaging (mpMRI)-ultrasound fusion, including sham biopsies in case of negative mpMRI. Outcome measurements and statistical analysis: Clinically significant PCa (csPCa), defined as group ≥2 on the International Society of Urological Pathology grading, was detected. Results and limitations: The overall prevalence of csPCa, irrespective of biopsy technique, was 37.4% (132/353) in our population. MRI-TBx were performed in 263/353 (74.5%) patients with suspicious mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The detection rates for csPCa were 39.5% for MRI-TBx and 42.9% for systematic biopsies. The added values, defined as the additional percentages of patients with csPCa detected by adding one biopsy technique, were 8.7% for the systematic biopsies and 5.3% for MRI-TBx. In patients with nonsuspicious mpMRI, five cases (6%) of csPCa were found by systematic biopsies. Conclusions: This study in biopsy-naïve patients suspected for PCa showed that systematic biopsies have added value to MRI-TBx alone in patients with mpMRI PI-RADS >2. Patient summary: We studied magnetic resonance imaging (MRI)-guided prostate biopsy for diagnosing prostate cancer and compared it with the standard method of prostate biopsy. Standard systematic biopsies cannot be omitted in patients with suspicious MRI, as they add to the detection of significant prostate cancer.

Positive predictive value of ultrasound in correctly identifying an inguinal hernia: a single-centered retrospective pilot study.

OBJECTIVES: To determine the clinical utility of preoperative ultrasound imaging for predicting an inguinal hernia in need of surgery. In addition, we aimed to identify factors associated with false positive (FP) ultrasound examinations. METHODS: In this retrospective pilot study, we included all 175 patients who underwent inguinal hernia surgery in our hospital in 2019 and of whom a positive preoperative ultrasound examination of the groin area was available. The positive predictive value (PPV) of the ultrasound examination was determined using inguinal hernia detected during surgery (yes/no) as golden standard. To identify possible predictive factors, we compared the characteristics of patients with a FP ultrasound with patients with a true positive (TP) ultrasound. RESULTS: PPV of ultrasound examinations to identify an inguinal hernia in need of surgery correctly was 90.9% (159/175). The patients with a FP ultrasound examination had a significantly higher body mass index (BMI) than the patients with a TP ultrasound examination (27.6 ± 4.2 vs 25.8 ± 2.3, p = 0.043). CONCLUSIONS: With a false positive percentage of 9.1%, there is still room for improvement of preoperative diagnostic imaging. Studies with larger cohorts are necessary to establish prediction models that have the potential to reduce FP ultrasound results.

Increased MR-guided high intensity focused ultrasound (MR-HIFU) sonication efficiency of uterine fibroids after carbetocin administration.

Purpose: We investigated whether administration of the long-acting uterus stimulant carbetocin increased intra-subject sonication efficiency during Magnetic Resonance image guided High Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids. Method: In this prospective cohort study, thirty women with symptomatic uterine fibroids undergoing MR-HIFU treatment were included between January 2018 and January 2019. Treatment started with three sonications on one side of the uterine fibroid. Subsequently, one ampoule of 1 mL carbetocin (100 µg/mL) was administered intravenously and treatment continued with three sonications on the other side of the uterine fibroid. We compared the intra-subject sonication efficiency, in terms of Energy Efficiency Factor (EEF), thermal dose volume and sonication time to ablate one cm3 of fibroid tissue, before and after carbetocin administration. Adverse events that occurred within 30 min after carbetocin administration were recorded. Results: Sonication efficiency improved after carbetocin administration as indicated by a significant decrease in EEF and sonication time (p = 0.006 and p = 0.001 respectively), and a significant increase in thermal dose volume reached (p = <0.001). Five women (16.7%) experienced temporary tachycardia, one women in combination with headache, within 30 min after carbetocin administration. Conclusion: Administration of the long-acting uterus stimulant carbetocin improved the MR-HIFU treatment intra-subject sonication efficiency in women with symptomatic uterine fibroids.

Synthetic CT for the planning of MR-HIFU treatment of bone metastases in pelvic and femoral bones: a feasibility study.

OBJECTIVES: Visualization of the bone distribution is an important prerequisite for MRI-guided high-intensity focused ultrasound (MRI-HIFU) treatment planning of bone metastases. In this context, we evaluated MRI-based synthetic CT (sCT) imaging for the visualization of cortical bone. METHODS: MR and CT images of nine patients with pelvic and femoral metastases were retrospectively analyzed in this study. The metastatic lesions were osteolytic, osteoblastic or mixed. sCT were generated from pre-treatment or treatment MR images using a UNet-like neural network. sCT was qualitatively and quantitatively compared to CT in the bone (pelvis or femur) containing the metastasis and in a region of interest placed on the metastasis itself, through mean absolute difference (MAD), mean difference (MD), Dice similarity coefficient (DSC), and root mean square surface distance (RMSD). RESULTS: The dataset consisted of 3 osteolytic, 4 osteoblastic and 2 mixed metastases. For most patients, the general morphology of the bone was well represented in the sCT images and osteolytic, osteoblastic and mixed lesions could be discriminated. Despite an average timespan between MR and CT acquisitions of 61 days, in bone, the average (± standard deviation) MAD was 116 ± 26 HU, MD - 14 ± 66 HU, DSC 0.85 ± 0.05, and RMSD 2.05 ± 0.48 mm and, in the lesion, MAD was 132 ± 62 HU, MD - 31 ± 106 HU, DSC 0.75 ± 0.2, and RMSD 2.73 ± 2.28 mm. CONCLUSIONS: Synthetic CT images adequately depicted the cancellous and cortical bone distribution in the different lesion types, which shows its potential for MRI-HIFU treatment planning. KEY POINTS: • Synthetic computed tomography was able to depict bone distribution in metastatic lesions. • Synthetic computed tomography images intrinsically aligned with treatment MR images may have the potential to facilitate MR-HIFU treatment planning of bone metastases, by combining visualization of soft tissues and cancellous and cortical bone.

Comparison of (Cost-)Effectiveness of Magnetic Resonance Image-Guided High-Intensity-Focused Ultrasound With Standard (Minimally) Invasive Fibroid Treatments: Protocol for a Multicenter Randomized Controlled Trial (MYCHOICE).

BACKGROUND: Magnetic resonance image-guided high-intensity-focused ultrasound (MR-HIFU) is a rather new, noninvasive option for the treatment of uterine fibroids. It is safe, effective, and has a very short recovery time. However, a lack of prospectively collected data on long-term (cost-)effectiveness of the MR-HIFU treatment compared with standard uterine fibroid care prevents the MR-HIFU treatment from being reimbursed for this indication. Therefore, at this point, when conservative treatment for uterine fibroid symptoms has failed or is not accepted by patients, standard care includes the more invasive treatments hysterectomy, myomectomy, and uterine artery embolization (UAE). Primary outcomes of currently available data on MR-HIFU treatment often consist of technical outcomes, instead of patient-centered outcomes such as quality of life (QoL), and do not include the use of the latest equipment or most up-to-date treatment strategies. Moreover, data on cost-effectiveness are rare and seldom include data on a societal level such as productivity loss or use of painkillers. Because of the lack of reimbursement, broad clinical implementation has not taken place, nor is the proper role of MR-HIFU in uterine fibroid care sufficiently clear. OBJECTIVE: The objective of our study is to determine the long-term (cost-)effectiveness of MR-HIFU compared with standard (minimally) invasive fibroid treatments. METHODS: The MYCHOICE study is a national, multicenter, open randomized controlled trial with randomization in a 2:1 ratio to MR-HIFU or standard care including hysterectomy, myomectomy, and UAE. The sample size is 240 patients in total. Women are included when they are 18 years or older, in premenopausal stage, diagnosed with symptomatic uterine fibroids, conservative treatment has failed or is not accepted, and eligible for MR-HIFU. Primary outcomes of the study are QoL 24 months after treatment and costs of treatment including direct health care costs, loss of productivity, and patient costs. RESULTS: Inclusion for the MYCHOICE study started in November 2020 and enrollment will continue until 2024. Data collection is expected to be completed in 2026. CONCLUSIONS: By collecting data on the long-term (cost-)effectiveness of the MR-HIFU treatment in comparison to current standard fibroid care, we provide currently unavailable evidence about the proper place of MR-HIFU in the fibroid treatment spectrum. This will also facilitate reimbursement and inclusion of MR-HIFU in (inter)national uterine fibroid care guidelines. TRIAL REGISTRATION: Netherlands Trial Register NL8863; https://www.trialregister.nl/trial/8863. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29467.

Systematic review of reproductive outcomes after High Intensity Focused Ultrasound treatment of uterine fibroids.

PURPOSE: Myomectomy is currently the gold standard for the treatment of uterine fibroids in women who desire pregnancy. However, this surgical fibroid removal has a long convalescence. Promising alternatives may be non-invasive High Intensity Focused Ultrasound (HIFU) under either MRI (MR-HIFU) or ultrasound guidance (USgHIFU). In this systematic review, an overview is provided of reproductive outcomes after these two relatively new ablation techniques. METHOD: A systematic literature search was performed to identify studies reporting reproductive outcomes after HIFU treatment of fibroids. Only peer reviewed, full papers were included. Outcomes included pregnancy-, live-birth- miscarriage and caesarian section rate, time to conceive, reported complications, and possible prognostic factors. RESULTS: In total 21 studies were included. Fourteen studies reported 124 pregnancies after MR-HIFU. Two placenta previas and no uterus ruptures were reported. Pregnancy rates were only retrospectively collected and ranged between 7% and 36%. Miscarriage rate in the oldest and largest prospective registry was 39%. After USgHIFU 366 pregnancies were reported with one fetal intrauterine death, six placenta previas and no uterus ruptures. The only prospective study reported a pregnancy rate of 47% and a miscarriage rate of 11%. Possible prognostic factors like age were not available in most studies. CONCLUSIONS: Based on the heterogeneous data currently available, reproductive outcomes after HIFU appear non-inferior to outcomes after the current standard of care. However, a (randomized) controlled trial comparing reproductive outcomes after HIFU and standard care is necessary to provide sufficient evidence on the preferred fibroid treatment for women with a pregnancy wish.

Combining radiotherapy and focused ultrasound for pain palliation of cancer induced bone pain; a stage I/IIa study according to the IDEAL framework.

BACKGROUND: Cancer induced bone pain (CIBP) strongly interferes with patient's quality of life. Currently, the standard of care includes external beam radiotherapy (EBRT), resulting in pain relief in approximately 60% of patients. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) is a promising treatment modality for CIBP. METHODS: A single arm, R-IDEAL stage I/IIa study was conducted. Patients presenting at the department of radiation oncology with symptomatic bone metastases in the appendicular skeleton, as well as in the sacrum and sternum were eligible for inclusion. All participants underwent EBRT, followed by MR-HIFU within 4 days. Safety and feasibility were assessed, and pain scores were monitored for 4 weeks after completing the combined treatment. RESULTS: Six patients were enrolled. Median age was 67 years, median lesion diameter was 56,5 mm. In all patients it was logistically possible to plan and perform the MR-HIFU treatment within 4 days after EBRT. All patients tolerated the combined procedure well. Pain response was reported by 5 out of 6 patients at 7 days after completion of the combined treatment, and stabilized on 60% at 4 weeks follow up. No treatment related serious adverse events occurred. CONCLUSION: This is the first study to combine EBRT with MR-HIFU. Our results show that combined EBRT and MR-HIFU in first-line treatment of CIBP is safe and feasible, and is well tolerated by patients. Superiority over standard EBRT, in terms of (time to) pain relief and quality of life need to be evaluated in comparative (randomized) study.

Development and clinical evaluation of a 3-step modified manipulation protocol for MRI-guided high-intensity focused ultrasound of uterine fibroids.

OBJECTIVES: The clinical applicability of magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids is often limited due to inaccessible fibroids or bowel interference. The aim of this study was to implement a newly developed 3-step modified manipulation protocol and to evaluate its influence on the number of eligible women and treatment failure rate. METHODS: From June 2016 to June 2018, 165 women underwent a screening MRI examination, 67 women of whom were consecutively treated with MR-HIFU at our institution. Group 1 (n = 20) was treated with the BRB manipulation protocol which consisted of sequential applications of urinary bladder filling, rectal filling, and urinary bladder emptying. Group 2 (n = 47) was treated using the 3-step modified manipulation protocol which included (1) the BRB maneuver with adjusted rectal filling by adding psyllium fibers to the solution; (2) Trendelenburg position combined with bowel massage; (3) the manual uterine manipulation (MUM) method for uterine repositioning. A comparison was made between the two manipulation protocols to evaluate differences in safety, the eligibility percentage, and treatment failure rate due to unsuccessful manipulation. RESULTS: After implementing the 3-step modified manipulation protocol, our ineligibility rate due to bowel interference or inaccessible fibroids decreased from 18% (16/88) to 0% (0/77). Our treatment failure rate due to unsuccessful manipulation decreased from 20% (4/20) to 2% (1/47). There were no thermal complications to the bowel or uterus. CONCLUSIONS: Implementation of the 3-step modified manipulation protocol during MR-HIFU therapy of uterine fibroids improved the eligibility percentage and reduced the treatment failure rate. TRIAL REGISTRATION: Registry number NL56182.075.16 KEY POINTS: • A newly developed 3-step modified manipulation protocol was successfully implemented without the occurrence of thermal complication to the bowel or uterus. • The 3-step modified manipulation protocol increased our eligibility percentage for MR-HIFU treatment of uterine fibroids. • The 3-step modified manipulation protocol reduced our treatment failure rate for MR-HIFU treatment of uterine fibroids.