Bilgin Keserci

Volumetric MR-HIFU ablation of uterine fibroids: Role of treatment cell size in the improvement of energy efficiency

PURPOSE To evaluate the energy efficiency of differently sized volumetric ablations in MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids. MATERIALS AND METHODS This study was approved by the institutional review board and informed consent was obtained from all participants. Ten symptomatic uterine fibroids (mean diameter 8.9 cm) in 10 women (mean age 42.2) were treated by volumetric MR-HIFU ablation under binary feedback control. The energy efficiency (mm3/J) of each sonication was calculated as the volume of lethal thermal dose (240 equivalent minutes at 43 °C) per unit acoustic energy applied. Operator-controllable parameters and signal intensity ratio of uterine fibroid to skeletal muscle on T2-weighted MR images were tested with univariate and multivariate analyses to discern which parameters significantly correlated with the ablation energy efficiency. RESULTS We analyzed a total of 236 sonications. The energy efficiency of the ablations was 0.42±0.25 mm3/J (range 0.004-1.18) with energy efficiency improving with the treatment cell size (4 mm, 0.06±0.06 mm3/J; 8 mm, 0.29±0.12 mm3/J; 12 mm, 0.58±0.18 mm3/J; 16 mm, 0.91±0.17 mm3/J). Treatment cell size (r=0.814, p<0.001), distance of ultrasound propagation (r=-0.151, p=0.020), sonication frequency (1.2 or 1.45 MHz; p<0.001), and signal intensity ratio (r=-0.205, p=0.002) proved to be significant by univariate analysis, while multivariate analysis revealed treatment cell size (B=0.075, p<0.001), US propagation distance (B=-6.928, p<0.001), and signal intensity ratio (B=-0.024, p=0.001) to be independently significant. CONCLUSION Energy efficiency in volumetric MR-HIFU ablation of uterine fibroids improves with increased treatment cell size, independent of other significant contributors such as distance of ultrasound propagation or signal intensity of the tumor on T2-weighted MR imaging.

Volumetric MR-guided High-Intensity Focused Ultrasound Ablation with a One-Layer Strategy to Treat Large Uterine Fibroids: Initial Clinical Outcomes

PURPOSE To evaluate initial clinical outcomes of volumetric magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) ablation by using a one-layer strategy to treat large (>10 cm in diameter) uterine fibroids, with investigation of the correlation between effectiveness of the one-layer strategy and dynamic contrast material-enhanced (DCE) MR parameters. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Twenty-seven women (mean age, 44.5 years) with 27 large uterine fibroids (mean diameter, 11.3 cm ± 1.4 [standard deviation] [range, 10.1-16.0 cm]; fibroid volume, 502.5 mL ± 214.3 [range, 253.8-1184.0 mL]) underwent volumetric MR-guided HIFU ablation with a one-layer strategy. (All treatment cells were placed in one coronal plane at a depth of half to anterior two-thirds of the anteroposterior dimension of fibroids.) Treatment time, immediate nonperfused volume (NPV), and effectiveness of a one-layer strategy (ratio of immediate NPV to total volume of treatment cells planned) correlating with baseline DCE MR parameters (volume transfer constant [K(trans)], fractional extravascular extracellular space, and fractional blood plasma volume [Pearson correlation test]), complications, 3-month follow-up volumes, and symptom severity score (SSS) changes (paired t test) were assessed retrospectively. RESULTS All treatments showed technical success in one session (mean treatment time, 166.2 minutes ± 38.9). NPV was 301.3 mL ± 119.1, which was 64.2% ± 19.9 (<50%, n = 4; ≥ 50%, n = 23) of fibroid volume. Ratio of immediate NPV to total volume of treatment cells (1.79 ± 0.61) negatively correlated with DCE MR imaging K(trans) values (r = -0.426, P = .017). Minor complications occurred in five patients (18.5% [thermal injury of abdominal wall, n = 3; 30-day leg numbness, n = 1; cystitis, n = 1]). At 3-month follow-up (n = 18), mean SSS had decreased from 37.4 at baseline to 24.0 (P < .001), and volume reduction ratio was 0.64 ± 0.15 (P < .001). CONCLUSION Volumetric MR-guided HIFU ablation with a one-layer strategy is safe and effective for treatment of large uterine fibroids. Effectiveness of this strategy showed a significant negative correlation with K(trans) values at baseline DCE MR imaging.

Dynamic contrast-enhanced magnetic resonance imaging predicts immediate therapeutic response of magnetic resonance-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids.

Objectives:To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in the prediction of the immediate therapeutic response of MR-guided high-intensity focused ultrasound (HIFU) therapy in the treatment of symptomatic uterine fibroids Materials and Methods:Institutional review board approved this study, and informed consent was obtained from all participants. A total of 10 symptomatic uterine fibroids (diameter: mean, 8.9 cm; range, 4.7–12 cm) in 10 female patients (mean age, 42.2 years) were treated with MR-HIFU therapy using the volumetric ablation technique. DCE-MRI and conventional contrast-enhanced MRI were obtained as a baseline and as an immediate follow-up study, respectively. After regions of interest of each treatment cell were properly registered to both MRI studies, DCE-MRI parameters (Ktrans, ve, vp) and operator-controllable therapy parameters (power, treatment cell size, sonication depth) were investigated on a cell-by-cell basis to reflect tissue inhomogeneity. Two types of ablation efficacy indices (volume of 240 equivalent minutes at 43°C/treatment-cell volume, nonperfused volume/treatment-cell volume) were then correlated with those parameters using multiple linear regression analysis to determine which factors were significant predictors for ablation efficacy. Results:We used 293 treatment cells (4 mm, n = 12; 8 mm, n = 115; 12 mm, n = 149; 16 mm, n = 17), and all of them were analyzable. Ablation efficacies were 1.06 ± 0.58 and 0.67 ± 0.39. Ktrans (B = −12.035, P < 0.001 and B = −11.516, P < 0.001, respectively) among DCE-MRI parameters and acoustic power (B = 0.008, P < 0.001; B = 0.010, P < 0.001, respectively) among therapy parameters were revealed to be independently significant predictors for both types of ablation efficacy. Conclusions:A higher Ktrans value at baseline DCE-MRI suggested a poor ablation efficacy of MR-HIFU therapy for symptomatic uterine fibroids.

MR Thermometry Analysis of Sonication Accuracy and Safety Margin of Volumetric MR Imaging–guided High-Intensity Focused Ultrasound Ablation of Symptomatic Uterine Fibroids

PURPOSE To evaluate the accuracy of the size and location of the ablation zone produced by volumetric magnetic resonance (MR) imaging-guided high-intensity focused ultrasound ablation of uterine fibroids on the basis of MR thermometric analysis and to assess the effects of a feedback control technique. MATERIALS AND METHODS This prospective study was approved by the institutional review board, and written informed consent was obtained. Thirty-three women with 38 uterine fibroids were treated with an MR imaging-guided high-intensity focused ultrasound system capable of volumetric feedback ablation. Size (diameter times length) and location (three-dimensional displacements) of each ablation zone induced by 527 sonications (with [n=471] and without [n=56] feedback) were analyzed according to the thermal dose obtained with MR thermometry. Prospectively defined acceptance ranges of targeting accuracy were ±5 mm in left-right (LR) and craniocaudal (CC) directions and ±12 mm in anteroposterior (AP) direction. Effects of feedback control in 8- and 12-mm treatment cells were evaluated by using a mixed model with repeated observations within patients. RESULTS Overall mean sizes of ablation zones produced by 4-, 8-, 12-, and 16-mm treatment cells (with and without feedback) were 4.6 mm±1.4 (standard deviation)×4.4 mm±4.8 (n=13), 8.9 mm±1.9×20.2 mm±6.5 (n=248), 13.0 mm±1.2×29.1 mm±5.6 (n=234), and 18.1 mm±1.4×38.2 mm±7.6 (n=32), respectively. Targeting accuracy values (displacements in absolute values) were 0.9 mm±0.7, 1.2 mm±0.9, and 2.8 mm±2.2 in LR, CC, and AP directions, respectively. Of 527 sonications, 99.8% (526 of 527) were within acceptance ranges. Feedback control had no statistically significant effect on targeting accuracy or ablation zone size. However, variations in ablation zone size were smaller in the feedback control group. CONCLUSION Sonication accuracy of volumetric MR imaging-guided high-intensity focused ultrasound ablation of uterine fibroids appears clinically acceptable and may be further improved by feedback control to produce more consistent ablation zones.

Uterine Fibroids: Postsonication Temperature Decay Rate Enables Prediction of Therapeutic Responses to MR Imaging-guided High-Intensity Focused Ultrasound Ablation

PURPOSE To determine whether intraprocedural thermal parameters as measured with magnetic resonance (MR) thermometry can be used to predict immediate or delayed therapeutic response after MR-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. MATERIALS AND METHODS Institutional review board approval and subject informed consent were obtained. A total of 105 symptomatic uterine fibroids (mean diameter, 8.0 cm; mean volume, 251.8 mL) in 71 women (mean age, 43.3 years; age range, 25-52 years) who underwent volumetric MR HIFU ablation were analyzed. Correlations between tumor-averaged intraprocedural thermal parameters (peak temperature, thermal dose efficiency [estimated volume of 240 equivalent minutes at 43°C divided by volume of treatment cells], and temperature decay rate after sonication) and the immediate ablation efficiency (ratio of nonperfused volume [NPV] at immediate follow-up to treatment cell volume) or ablation sustainability (ratio of NPV at 3-month follow-up to NPV at immediate follow-up) were assessed with linear regression analysis. RESULTS A total of 2818 therapeutic sonications were analyzed. At immediate follow-up with MR imaging (n = 105), mean NPV-to-fibroid volume ratio and ablation efficiency were 0.68 ± 0.26 (standard deviation) and 1.35 ± 0.75, respectively. A greater thermal dose efficiency (B = 1.894, P < .001) and slower temperature decay rate (B = -1.589, P = .044) were independently significant factors that indicated better immediate ablation efficiency. At 3-month follow-up (n = 81), NPV had decreased to 43.1% ± 21.0 of the original volume, and only slower temperature decay rate was significantly associated with better ablation sustainability (B = -0.826, P = .041). CONCLUSION The postsonication temperature decay rate enables prediction of both immediate and delayed therapeutic responses, whereas thermal dose efficiency enables prediction of immediate therapeutic response to MR HIFU ablation of uterine fibroids.

Techniques to expand patient selection for MRI-guided high-intensity focused ultrasound ablation of uterine fibroids.

OBJECTIVE MRI-guided high-intensity focused ultrasound (HIFU) ablation is increasingly adopted for treating symptomatic uterine fibroids. As a noninvasive therapy performed on an outpatient basis, it has been viewed by patients to have distinct advantages over other treatment options. However, its breadth of clinical application is still limited. To address this issue, various techniques have been implemented. CONCLUSION In this article, we discuss techniques that contribute to widening patient selection for MRI-guided HIFU therapy of uterine fibroids.

Screening Magnetic Resonance Imaging-Based Prediction Model for Assessing Immediate Therapeutic Response to Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids.

ObjectivesThe aim of this study was to fit and validate screening magnetic resonance imaging (MRI)–based prediction models for assessing immediate therapeutic responses of uterine fibroids to MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation. Materials and MethodsInformed consent from all subjects was obtained for our institutional review board–approved study. A total of 240 symptomatic uterine fibroids (mean diameter, 6.9 cm) in 152 women (mean age, 43.3 years) treated with MR-HIFU ablation were retrospectively analyzed (160 fibroids for training, 80 fibroids for validation). Screening MRI parameters (subcutaneous fat thickness [mm], x1; relative peak enhancement [%] in semiquantitative perfusion MRI, x2; T2 signal intensity ratio of fibroid to skeletal muscle, x3) were used to fit prediction models with regard to ablation efficiency (nonperfused volume/treatment cell volume, y1) and ablation quality (grade 1-5, poor to excellent, y2), respectively, using the generalized estimating equation method. Cutoff values for achievement of treatment intent (efficiency >1.0; quality grade 4/5) were determined based on receiver operating characteristic curve analysis. Prediction performances were validated by calculating positive and negative predictive values. ResultsGeneralized estimating equation analyses yielded models of y1 = 2.2637 − 0.0415x1 − 0.0011x2 − 0.0772x3 and y2 = 6.8148 − 0.1070x1 − 0.0050x2 − 0.2163x3. Cutoff values were 1.312 for ablation efficiency (area under the curve, 0.7236; sensitivity, 0.6882; specificity, 0.6866) and 4.019 for ablation quality (0.8794; 0.7156; 0.9020). Positive and negative predictive values were 0.917 and 0.500 for ablation efficiency and 0.978 and 0.600 for ablation quality, respectively. ConclusionsScreening MRI-based prediction models for assessing immediate therapeutic responses of uterine fibroids to MR-HIFU ablation were fitted and validated, which may reduce the risk of unsuccessful treatment.

Volume transfer constant (Ktrans) maps from dynamic contrast enhanced MRI as potential guidance for MR-guided high intensity focused ultrasound treatment of hypervascular uterine fibroids

Higher perfusion of uterine fibroids at baseline is recognized as cause for poor efficacy of MR-guided high intensity focused ultrasound (HIFU) ablation, and higher acoustic power has been suggested for the treatment of high-perfused areas inside uterine fibroids. However, considering the heterogeneously vascular distribution inside the uterine fibroids especially with hyper vascularity, it is not easy to choose the correct therapy acoustic power for every part inside fibroids. In our study, we presented two cases of fibroids with hyper vascularity, to show the differences between them with different outcomes. Selecting higher therapy acoustic powers to ablate high-perfused areas efficiently inside fibroids might help achieving good ablation results. Volume transfer constant (K(trans)) maps from dynamic contrast-enhanced (DCE) imaging at baseline helps visualizing perfusion state inside the fibroids and locating areas with higher-perfusion. In addition, with the help of K(trans) maps, appropriate therapy acoustic power could be selected by the result of initial test and therapy sonications at different areas with significantly different perfusion state inside fibroids.

The role of T1 perfusion-based classification in magnetic resonance-guided high-intensity focused ultrasound ablation of uterine fibroids

AbstractObjectiveTo comparatively evaluate the role of magnetic resonance (MR) T1 perfusion-based time–signal intensity (SI) curves of fibroid tissue and the myometrium in classification of fibroids for predicting treatment outcomes of high-intensity focused ultrasound (HIFU) treatment.MethodsThe fibroids of 74 women who underwent MR-HIFU treatment were classified into group A (time–SI curve of fibroid lower than that of the myometrium) and group B (time–SI curve of fibroid equal to or higher than that of the myometrium). Non-perfused volume (NPV) ratios immediately after treatment and fibroid volume reduction ratios and symptom severity scores (SSS) at the 6-month follow-up were retrospectively assessed.ResultsThe immediate NPV ratios in groups A and B were 95.3 ± 6.3% (n = 62) and 63.8 ± 11% (n = 12), respectively. At the 6-month follow-up, the fibroid volume reduction ratios in groups A and B were 0.52 ± 0.14 (n = 50) and 0.07 ± 0.14 (n = 11), with the corresponding improvement in mean transformed SSS being 0.86 ± 0.14 and 0.19 ± 0.3, respectively. No serious adverse effects were reported.ConclusionsOur novel classification method could play an important role in classifying fibroids for predicting the immediate outcomes of HIFU treatment.Key Points• MRI is an important modality for outcome prediction in HIFU treatment • Patient selection is a significant factor for achieving high NPV ratio • NPV ratio is very strongly correlated with T1 perfusion-based classification • T1 perfusion-based classification is a strong predictor of treatment outcome

T2*‐weighted imaging in the assessment of the non‐perfused volume of uterine fibroids following magnetic resonance‐guided high‐intensity focused ultrasound ablation

Magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) is applied widely in the ablation of symptomatic uterine fibroids [1–4]. Contrast-enhanced T1-weighted imaging (CE-T1WI) has been used in the assessment of the ablated areas of uterine fibroid, called the non-perfused volume (NPV), immediately following HIFU ablation and during follow-up. The present study details a case employing fast field echo T2*-weighted imaging (T2*WI) without the use of contrast agent for assessing NPV of fibroids in response to HIFU therapy, making a comparison with CE-T1WI. To our knowledge, this is the first report of this nature. A 45-year-old woman presenting with abdominal pain with uterine fibroids was treated by HIFU ablation. MR scanning and HIFU therapy were conducted using an Achieva TX 3 T MR scanner (Philips Healthcare, Best, The Netherlands). T2*WI (repetition time/echo time: 837/24 ms; slice thickness: 5 mm with a 1-mm gap; field of view: 240 × 240 mm; matrix: 320 × 250; flip angle: 24°) and CE-T1WI techniques were applied before and 3 minutes after the injection of contrast agents, respectively. The geometric parameters of T2*WI and CE T1WI were the same, including the scanning location and number of slices. T2*WI and CE-T1WI were compared slice by slice at the same location in the patient. The images produced using T2*WI had a high image quality and the NPV inside uterine fibroids could be visualized with clear margins on each slice, both during ablation and during follow-up. The majority of the NPV margins were irregular, but the details around the margins were almost exactly the same when employing T2*WI as CE-T1WI (Fig. 1). Using T2*WI, a dark-line around the NPV margin can be seen clearly; this might be due to surrounding micro hemorrhage. This appearance seems to make the boundary between NPV and fibroid tissue clearer with T2*WI in comparison with CE-T1WI. Additionally, two radiologists were asked to independently calculate the NPV areas on each slice from both T2*WI and CE-T1WI of the fibroids, with a paired t-test used to analyze the results; a P value of b0.05 was considered statistically significant. The statistical analysis showed no significant differences in the radiologists’ calculated NPVs between T2*WI and CE-T1WI of the fibroids (first fibroid: t1 = –1.063, P1 = 0.296; second fibroid: t2 = 0.375, P2 = 0.714). The present case demonstrated the feasibility of T2*WI in the assessment of the ablated volume of fibroids treated with HIFU. As an alternative to CE-T1WI, T2*WI without the use of a contrast agent might be a very promising method in assessing NPV inside uterine fibroids following HIFU ablation, both in real-time and during follow-up after the procedure.