Implementing ABCD studyⓇ MRI sequences for multi-site cohort studies: Practical guide to necessary steps, preprocessing methods, and challenges.

Large multi-site studies that combine magnetic resonance imaging (MRI) data across research sites present exceptional opportunities to advance neuroscience research. However, scanner or site variability and non-standardised image acquisition protocols, data processing and analysis pipelines can adversely affect the reliability and repeatability of MRI derived brain measures. We implemented a standardised MRI protocol based on that used in the Adolescent Brain Cognition Development (ABCD)Ⓡ study in two sites, and across four MRI scanners. Twice repeated measurements of a single healthy volunteer were obtained in two sites and in four 3T MRI scanners (vendors: Siemens, Philips, and GE). Imaging data included anatomical scans (T1 weighted, T2 weighted), diffusion weighted imaging (DWI) and resting state functional MRI (rs-fMRI). Standardised containerized pipelines were utilised to pre-process the data and different image quality metrics and test-retest variability of different brain metrics were evaluated. The implementation of the MRI protocols was possible with minor adjustments in acquisition (e.g. repetition time (TR), higher b-values) and exporting (DICOM formats) of images due to different technical performance of the scanners. This study provides practical insights into the implementation of standardised sequences and data processing for multisite studies, showcase the benefits of containerised preprocessing tools, and highlights the need for careful optimisation of multisite image acquisition.

Histological findings in resected leiomyomas following MR-HIFU treatment, single-institution data from seven patients with unfavorable focal therapy.

PURPOSE: Magnetic resonance - high-intensity focused ultrasound (MR-HIFU) is a noninvasive treatment option for symptomatic uterine leiomyomas. Currently, pretreatment MRI is used to assess tissue characteristics and predict the most likely therapeutic response for individual patients. However, these predictions still entail significant uncertainties. The impact of tissue properties on therapeutic outcomes remains poorly understood and detailed knowledge of the histological effects of ultrasound ablation is lacking. Investigating these aspects could aid in optimizing patient selection, enhancing treatment effects and improving treatment outcomes. METHODS AND MATERIALS: We present seven patients who underwent MR-HIFU treatment for leiomyoma followed by second-line surgical treatment. Tissue samples obtained during the surgery were stained with hematoxylin and eosin, Masson's trichrome and Herovici to evaluate general morphology, fibrosis and collagen deposition of leiomyomas. Immunohistochemical CD31, Ki-67 and MMP-2 stainings were performed to study vascularization, proliferation and matrix metalloproteinase-2 protein expression in leiomyomas, respectively. RESULTS: The clinical characteristics and radiological findings of the leiomyomas prior to treatment as well as qualitative histological findings after the treatment are presented and discussed in the context of current literature. A tentative model for volume reduction is presented. CONCLUSION: These findings provide insights into potential factors contributing to suboptimal therapeutic outcomes and the variability in histological changes following treatment.

Evolution of non-perfused volume after transurethral ultrasound ablation of prostate: A retrospective 12-month analysis.

Background: A detailed understanding of the non-perfused volume (NPV) evolution after prostate ablation therapy is lacking. The impact of different diseased prostate tissues on NPV evolution post-ablation is unknown. Purpose: To characterize the NPV evolution for three treatment groups undergoing heat-based prostate ablation therapy, including benign prostatic hyperplasia (BPH), primary prostate cancer (PCa), and radiorecurrent PCa. Materials and methods: Study design and data analysis were performed retrospectively. All patients received MRI-guided transurethral ultrasound ablation (TULSA). 21 BPH, 28 radiorecurrent PCa and 40 primary PCa patients were included. Using the T1-weighted contrast-enhanced MR image, the NPV was manually contoured by an experienced radiologist. All patients received an MRI immediately following the ablation. Follow-up included MRI at 3- and 12 months for BPH and radiorecurrent PCa patients and at 6- and 12 months for primary PCa patients. Results: A significant difference between BPH and radiorecurrent PCa patients was observed at three months (p < 0.0001, Wilcoxon rank sum test), with the median NPV decreasing by 77 % for BPH patients but increasing by 4 % for radiorecurrent PCa patients. At six months, the median NPV decreased by 97 % for primary PCa. Across all groups, although 40 % of patients had residual NPV at 12 months, it tended to be < 1 mL. Conclusion: The resolution of necrotic tissue after ablation was markedly slower for irradiated than treatment-naïve prostate tissue. These results may account for the increased toxicity observed after radiorecurrent salvage therapy. By 12 months, most necrotic prostate tissue had disappeared in every treatment group.

Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve.

INTRODUCTION: Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH). MATERIAL AND METHODS: Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24-48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied. RESULTS: The median AMH level before the HIFU treatment was 1.20 (range: 0.1-7.75 ug/L) and after the treatment 1.23 (range: 0.1-8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment. CONCLUSIONS: MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels.

Magnetic resonance imaging-guided transurethral ultrasound ablation for benign prostatic hyperplasia: 12-month clinical outcomes of a phase I study.

OBJECTIVES: To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO). PATIENTS AND METHODS: An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification. RESULTS: A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA. CONCLUSION: TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.

Fiducial markers and their impact on ablation outcome for patients treated with MR-guided transurethral ablation (TULSA): a retrospective technical analysis.

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

Feasibility of T2 relaxation time in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids.

PURPOSE: The aim of this study was to assess the feasibility of T2 relaxation time in predicting the immediate technical outcome i.e., nonperfused volume ratio (NPVr) of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it with existing T2-weighted imaging methods (Funaki classification and scaled signal intensity, SSI). MATERIALS AND METHODS: 30 patients with 32 uterine fibroids underwent an MRI study including a quantitative T2 relaxation time measurement prior to MRgHIFU treatment. T2 relaxation times were measured with a multi-echo fast imaging-based technique with 16 echoes. The correlation between pretreatment values of the uterine fibroids and treatment outcomes, that is nonperfused volume ratios (NPVr), was assessed with nonparametric statistical measures. T2 relaxation time-based method was compared to existing T2-weighted imaging-based methods using receiver-operating-characteristics (ROC) curve analysis and Chi-square test. RESULTS: Nonparametric measures of association revealed a statistically significant negative correlation between T2 relaxation time values and NPVr. The T2 relaxation time classification (T2 I, T2 II, and T2 III) resulted in the whole model p-value of 0.0019, whereas the Funaki classification resulted in a p-value of 0.56. The T2 relaxation time classification (T2 I and T2 II) achieved a whole model of a p-value of 0.0024, whereas the SSI classification had a p-value of 0.0749. CONCLUSIONS: A longer T2 relaxation time of the fibroid prior to treatment correlated with a lower NPVr. Based on our results, the T2 relaxation time classifications seem to outperform the Funaki classification and the SSI method.

Feasibility of apparent diffusion coefficient in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids - a comparison with the Funaki classification.

PURPOSE: To investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification. MATERIALS AND METHODS: Forty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of <30%, 30-80%, or >80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test. RESULTS: A statistically significant negative correlation (Spearman's ρ = -0.31, p-value < 0.05) was detected between ADC values and NPV ratios. ROC curve analysis indicated that optimal ADC cutoff values of 980 × 10-6mm2/s (NPVr > 80%) and 1800 × 10-6mm2/s (NPVr < 30%) made it possible to classify fibroids into three groups: ADC I (NPVr > 80%), ADC II (NPVr 30-80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (p-value = 0.0007) and 0.62 for the Funaki classification (p-value = 0.0527). CONCLUSIONS: Lower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol.

Acute and subacute prostate MRI findings after MRI-guided transurethral ultrasound ablation of prostate cancer.

BACKGROUND: Magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) is an emerging method for treatment of localized prostate cancer (PCa). TULSA-related subacute MRI findings have not been previously characterized. PURPOSE: To evaluate acute and subacute MRI findings after TULSA treatment in a treat-and-resect setting. MATERIAL AND METHODS: Six men with newly diagnosed MRI-visible and biopsy-concordant clinically significant PCa were enrolled and completed the study. Eight lesions classified as PI-RADS 3-5 were focally ablated using TULSA. One- and three-week follow-up MRI scans were performed between TULSA and robot-assisted laparoscopic prostatectomy. RESULTS: TULSA-related hemorrhage was detected as a subtle T1 hyperintensity and more apparent T2 hypointensity in the MRI. Both prostate volume and non-perfused volume (NPV) markedly increased after TULSA at one week and three weeks after treatment, respectively. Lesion apparent diffusion coefficient values increased one week after treatment and decreased nearing the baseline values at the three-week MRI follow-up. CONCLUSION: The optimal timing of MRI follow-up seems to be at the earliest at three weeks after treatment, when the post-procedural edema has decreased and the NPV has matured. Diffusion-weighted imaging has little or no added diagnostic value in the subacute setting.

Imaging-based internal body temperature measurements: The journal Temperature toolbox.

Noninvasive imaging methods of internal body temperature are in high demand in both clinical medicine and physiological research. Thermography and thermometry can be used to assess tissue temperature during thermal therapies: ablative and hyperthermia treatments to ensure adequate temperature rise in target tissues but also to avoid collateral damage by heating healthy tissues. In research use, measurement of internal body temperature enables us the production of thermal maps on muscles, internal organs, and other tissues of interest. The most used methods for noninvasive imaging of internal body temperature are based on different parameters acquired with magnetic resonance imaging, ultrasound, computed tomography, microwave radiometry, photoacoustic imaging, and near-infrared spectroscopy. In the current review, we examine the aforementioned imaging methods, their use in estimating internal body temperature in vivo with their advantages and disadvantages, and the physical phenomena the thermography or thermometry modalities are based on.

Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation.

INTRODUCTION: Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique. MATERIALS AND METHODS: 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401. RESULTS: Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin (p ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups (p = 0.04). CONCLUSION: Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.

Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer.

PURPOSE: Locally advanced prostate cancer can cause bladder outlet obstruction, gross hematuria and frequent hospitalization. While these complications are commonly treated by palliative transurethral resection of the prostate, the improvement is often insufficient. The purpose of this study was to evaluate the safety and feasibility of MRI-guided transurethral ultrasound ablation as an alternative palliative treatment option (pTULSA) for men suffering from symptomatic locally advanced prostate cancer. METHODS: This prospective, phase one study included 10 men in need of palliative surgical intervention due to urinary retention and gross hematuria caused by locally advanced prostate cancer. Patients were followed for 1 year at 3-month intervals. Time without catheter, time without hematuria, reduction in hospitalization time, and adverse events were measured. RESULTS: Ten patients with locally advanced prostate cancer were enrolled, all having continuous catheterization due to urinary retention and nine had gross hematuria before treatment. At 1 week post-pTULSA five patients were catheter-free. At last follow-up catheter-free and gross hematuria-free rates were 70% and 100%, respectively. Average hospitalization time from local complications reduced from 7.3 to 1.4 days in the 6 months before and after pTULSA. No > Grade 2 treatment related adverse events were reported, with all five being urinary tract infections. CONCLUSIONS: pTULSA appears safe and feasible for palliative ablation of locally advanced prostate cancer. The therapy seems to accomplish long-term hematuria control, can relieve bladder outlet obstruction in selected patients, and seems to reduce the burden of hospitalization due to local complications. Trial Registration Number: NCT03350529.

Salvage Magnetic Resonance Imaging-guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer: 12-Month Functional and Oncological Results.

BACKGROUND: Up to half of all men who undergo primary radiotherapy for localized prostate cancer (PCa) experience local recurrence. OBJECTIVE: To evaluate the safety and early functional and oncological outcomes of salvage magnetic resonance imaging-guided transurethral ultrasound ablation (sTULSA) for men with localized radiorecurrent PCa. DESIGN SETTING AND PARTICIPANTS: This prospective, single-center phase 1 study (NCT03350529) enrolled men with biopsy-proven localized PCa recurrence after radiotherapy. Multiparametric magnetic resonance imaging (mpMRI) and 18F prostate-specific membrane antigen-1007 (18F PSMA-1007) positron emission tomography (PET)-computed tomography (CT) were used to confirm organ-confined disease localization. Patients underwent either whole-gland or partial sTULSA, depending on their individual tumor characteristics. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were followed at 3-mo intervals. Adverse events (AEs, Clavien-Dindo scale), functional status questionnaires (Expanded Prostate Cancer Index [EPIC]-26, International Prostate Symptom Score, International Index of Erectile Function-5), uroflowmetry, and prostate-specific antigen (PSA) were assessed at every visit. Disease control was assessed at 1 yr using mpMRI and 18F-PSMA-1007 PET-CT, followed by prostate biopsies. RESULTS AND LIMITATIONS: Eleven patients (median age 69 yr, interquartile range [IQR] 68-74) underwent sTULSA (3 whole-gland, 8 partial sTULSA) and have completed 12-mo follow-up. Median PSA was 7.6 ng/ml (IQR 4.9-10) and the median time from initial PCa diagnosis to sTULSA was 11 yr (IQR 9.5-13). One grade 3 and three grade 2 AEs were reported, related to urinary retention and infection. Patients reported a modest degradation in functional status, most significantly a 20% decline in the EPIC-26 irritative/obstructive domain at 12 mo. A decline in maximum flow rate (24%) was also observed. At 1 yr, 10/11 patients were free of any PCa in the targeted ablation zone, with two out-of-field recurrences. Limitations include the nonrandomized design, limited sample size, and short-term oncological outcomes. CONCLUSIONS: sTULSA appears to be safe and feasible for ablation of radiorecurrent PCa, offering encouraging preliminary oncological control. PATIENT SUMMARY: We present safety and 1-yr functional and oncological outcomes of magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) as a salvage treatment for local prostate cancer recurrence after primary radiation. Salvage TULSA is safe and shows the ability to effectively ablate prostate cancer recurrence, with acceptable toxicity.

Feasibility of MRI-guided transurethral ultrasound for lesion-targeted ablation of prostate cancer.

Background: MRI-guided transurethral ultrasound ablation (TULSA) has been evaluated for organ-confined prostate cancer (PCa). The purpose of this study was to assess the safety and toxicity, accuracy and short-term evolution of cell-death after lesion-targeted TULSA.Methods: This prospective, registered, Phase-I treat-and-3-week-resect-study enrolled six patients with MRI-visible-biopsy-concordant PCa. Lesions were targeted using TULSA with radical intent, except near neurovascular bundles (NVB). Robot-assisted-laparoscopic-prostatectomy (RALP) was performed at 3 weeks. Post-TULSA assessments included MRI (1 and 3 weeks), adverse events and quality-of-life (QoL) to 3 weeks, followed by RALP and whole-mount-histology. Treatment accuracy and demarcation of thermal injury were assessed using MRI and histology.Results: Six patients (median age = 70 years, prostate volume = 60 ml, PSA = 8.9 ng/ml) with eight biopsy-confirmed MRI-lesions (PIRADS ≥3) were TULSA-treated without complications (median sonication and MRI-times of 17 and 117 min). Foley-catheter removal was uneventful at 2-3 days. Compared to baseline, no differences in QoL were noted at 3 weeks. During follow-up, MRI-derived non-perfused-volume covered ablated targets and increased 36% by 3 weeks, correlating with necrosis-area on histology. Mean histological demarcation between complete necrosis and outer-limit-of-thermal-injury was 1.7 ± 0.4 mm. Coagulation necrosis extended to capsule except near NVB, where 3 mm safety-margins were applied. RALPs were uncomplicated and histopathology showed no viable cancer within the ablated tumor-containing target.Conclusions: Lesion-targeted TULSA demonstrates accurate and safe ablation of PCa. A significant increase of post-TULSA non-perfused-volume was observed during 3 weeks follow-up concordant with necrosis on histology. TULSA achieved coagulation necrosis of all targeted tissues. A limitation of this treat-and-resect-study-design was conservative treatment near NVB in patients scheduled for RALP.

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells.

Purpose: Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. Methods and materials: A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. Results: One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Conclusion: Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.

Comprehensive feature selection for classifying the treatment outcome of high-intensity ultrasound therapy in uterine fibroids.

The study aim was to utilise multiple feature selection methods in order to select the most important parameters from clinical patient data for high-intensity focused ultrasound (HIFU) treatment outcome classification in uterine fibroids. The study was retrospective using patient data from 66 HIFU treatments with 89 uterine fibroids. A total of 39 features were extracted from the patient data and 14 different filter-based feature selection methods were used to select the most informative features. The selected features were then used in a support vector classification (SVC) model to evaluate the performance of these parameters in predicting HIFU therapy outcome. The therapy outcome was defined as non-perfused volume (NPV) ratio in three classes: <30%, 30-80% or >80%. The ten most highly ranked features in order were: fibroid diameter, subcutaneous fat thickness, fibroid volume, fibroid distance, Funaki type I, fundus location, gravidity, Funaki type III, submucosal fibroid type and urinary symptoms. The maximum F1-micro classification score was 0.63 using the top ten features from Mutual Information Maximisation (MIM) and Joint Mutual Information (JMI) feature selection methods. Classification performance of HIFU therapy outcome prediction in uterine fibroids is highly dependent on the chosen feature set which should be determined prior using different classifiers.

High-Intensity Focused Ultrasound Therapy in the Uterine Fibroid: A Clinical Case Study of Poor Heating Efficacy.

A clinical case study of high-intensity focused ultrasound (HIFU) treatment in the uterine fibroid was conducted. During the therapy, poor heating efficacy was observed which could be attributed to several factors such as the local perfusion rate, patient-specific anatomy or changes in acoustic parameters of the ultrasound field. In order to determine the cause of the diminished heating, perfusion analyses and ultrasound simulations were conducted using the magnetic resonance imaging (MRI) data from the treatment. The perfusion analysis showed high local perfusion rate in the myoma (301.0 ± 25.6 mL/100 g/min) compared to the surrounding myometrium (233.8 ± 16.2 mL/100 g/min). The ultrasound simulations did not show large differences in the focal point shape or the acoustic pressure (2.07 ± 0.06 MPa) when tilting the transducer. However, a small shift (-2.2 ± 1.3 mm) in the axial location of the focal point was observed. The main causes for the diminished heating were likely the high local perfusion and ultrasound attenuation due to the deep location of the myoma.

Wedged gel pad for bowel manipulation during MR-guided high-intensity focused ultrasound therapy to treat uterine fibroids: a case report.

BACKGROUND: Magnetic resonance guided high-intensity focused ultrasound (MR-HIFU) therapy is not feasible in all patients with uterine fibroids because of limiting anatomical factors such as scar tissue, bowel loops or other obstacles in the sonication path. These may prevent the treatment or limit the treatment window, and therefore, also the volume where HIFU therapy can be delivered. Bowel loops present a particular problem because of bowel gas bubbles and hard particles which may cause reflection or absorption of ultrasound energy, potentially leading to thermal damage and even bowel perforation. Most commonly used techniques for bowel repositioning are bladder and/or rectum filling but these are not always sufficient to reposition the bowel loops. With more efficient bowel repositioning technique, the number of eligible patients for MR-HIFU treatment could be increased, and therapy efficacy be improved in cases where bowel loops limit the treatment window. CASE PRESENTATION: A wedged exterior gel pad was used in two patients presented with in total of four symptomatic fibroids undergoing MR-HIFU treatment when bladder and/or rectum filling was not sufficient to reposition the bowel loops. No severe adverse effects were observed in these cases. The non-perfused volume ratios (NPVs) immediately after treatment were 86% and 39% for the first patient, and 3% for the second patient. CONCLUSIONS: Our preliminary experience suggests that the use of a wedged gel pad during MR-HIFU treatment could be an effective tool to manipulate the bowels in cases where the bladder and/or rectum filling is not sufficient to reposition the bowel loops. A wedged gel pad could also be used in other situations to achieve better treatment coverage to the uterine fibroid.

Transurethral ultrasound therapy of the prostate in the presence of calcifications: A simulation study.

PURPOSE: Transurethral ultrasound therapy is an investigational treatment modality which could potentially be used for the localized treatment of prostate cancer. One of the limiting factors of this therapy is prostatic calcifications. These attenuate and reflect ultrasound and thus reduce the efficacy of the heating. The aim of this study is to investigate how prostatic calcifications affect therapeutic efficacy, and to identify the best sonication strategy when calcifications are present. METHODS: Realistic computational models were used on clinical patient data in order to simulate different therapeutic situations with naturally occurring calcifications as well as artificial calcifications of different sizes (1-10 mm) and distances (5-15 mm). Furthermore, different sonication strategies were tested in order to deliver therapy to the untreated tissue regions behind the calcifications. RESULTS: The presence of calcifications in front of the ultrasound field was found to increase the peak pressure by 100% on average while the maximum temperature only rose by 9% during a 20-s sonication. Losses in ultrasound energy were due to the relatively large acoustic impedance mismatch between the prostate tissue and the calcifications (1.63 vs 3.20 MRayl) and high attenuation coefficient (0.78 vs 2.64 dB/MHz1.1 /cm), which together left untreated tissue regions behind the calcifications. In addition, elevated temperatures were seen in the region between the transducer and the calcifications. Lower sonication frequencies (1-4 MHz) were not able to penetrate through the calcifications effectively, but longer sonication durations (20-60 s) with selective transducer elements were effective in treating the tissue regions behind the calcifications. CONCLUSIONS: Prostatic calcifications limit the reach of therapeutic ultrasound treatment due to reflections and attenuation. The tissue regions behind the calcifications can possibly be treated using longer sonication durations combined with proper transducer element selection. However, caution should be taken with calcifications located close to sensitive organs such as the urethra, bladder neck, or rectal wall.