What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

MRI-Guided Focused Ultrasound of Osseous Metastases: Treatment Parameters Associated With Successful Pain Reduction.

BACKGROUND: A phase 3 multicenter trial demonstrated that magnetic resonance imaging (MRI)-guided focused ultrasound (US) is a safe, noninvasive treatment that alleviated pain from bone metastases. However, outcomes varied among institutions (from 0%-100% treatment success). PURPOSE: The aim of this study was to identify patient selection, technical treatment, and imaging parameters that predict successful pain relief of osseous metastases after MRI-guided focused US. MATERIALS AND METHODS: This was a secondary analysis of a phase 3 clinical study that included participants who received MRI-guided focused US treatment for painful osseous metastases. Noncontrast CT was obtained before treatment. T2-weighted and T1-weighted postcontrast MRIs at 1.5 T or 3 T were obtained before, at the time of, and at 3 months after treatment. Numerical Rating Scale pain scores and morphine equivalent daily dose data were obtained over a 3-month follow-up period. At the 3-month endpoint, participants were categorized as pain relief responders or nonresponders based on Numerical Rating Scale and morphine equivalent daily dose data. Demographics, technical parameters, and imaging features associated with pain relief were determined using stepwise univariable and multivariable models. Responder rates between the subgroup of participants with all predictive parameters and that with none of the parameters were compared using Fisher exact test. RESULTS: The analysis included 99 participants (mean age, 59 ± 14 years; 56 women). The 3 variables that predicted successful pain relief were energy density on the bone surface (EDBS) (P = 0.001), the presence of postprocedural periosteal devascularization (black band, BB+) (P = 0.005), and female sex (P = 0.02). The subgroup of participants with BB+ and EDBS greater than 5 J/mm2 had a larger decrease in mean pain score (5.2; 95% confidence interval, 4.6-5.8) compared with those without (BB-, EDBS ≤ 5 J/mm2) (1.1; 95% confidence interval, 0.8-3.0; P < 0.001). Participants with all 3 predictive variables had a pain relief responder rate of 93% compared with 0% in participants having none of the predictive variables (P < 0.001). CONCLUSIONS: High EDBS during treatment, postprocedural periosteal devascularization around the tumor site (BB+), and female sex increased the likelihood of pain relief after MRI-guided focused US of osseous metastasis.

Prolonged heating in nontargeted tissue during MR-guided focused ultrasound of bone tumors.

BACKGROUND: Thermal dosimetry during MR-guided focused ultrasound (MRgFUS) of bone tumors underpredicts ablation zone. Intraprocedural understanding of heat accumulation near bone is needed to prevent undesired treatment of nontargeted tissue. HYPOTHESIS: Temperature decay rates predict prolonged, spatially varying heating during MRgFUS bone treatments. STUDY TYPE: Prospective case series. PATIENTS: Nine patients with localized painful bone tumors (five bone metastasis, four osteoid osteomas), were compared with five patients with uterine fibroid tumors treated using MRgFUS. FIELD STRENGTH/SEQUENCE: Proton resonance frequency shift thermometry using 2D-GRE with echo-planar imaging at 3 T. ASSESSMENT: Tissue response was derived by fitting data from extended thermometry acquisitions to a decay model. Decay rates and time to peak temperature (TTP) were analyzed in segmented zones between the bone target and skin. Decay rates were used to calculate intersonication cooling times required to return to body temperature; these were compared against conventional system-mandated cooling times. STATISTICAL TESTS: Kolmogorov-Smirnov tests for normality, and Student's t-test was used to compare decay rates. Spatial TTP delay and predicted cooling times used Wilcoxon signed rank tests. P < 0.05 was significant. RESULTS: Tissue decay rates in bone tumor patients were 3.5 times slower than those in patients with fibroids (τbone = 0.037 ± 0.012 vs. τfibroid = 0.131 ± 0.010, P < 0.05). Spatial analysis showed slow decay rates effecting baseline temperature as far as 12 mm away from the bone surface, τ4 = 0.015 ± 0.026 (median ± interquartile range [IQR]). Tissue within 9 mm of bone experienced delayed TTP (P < 0.01). In the majority of bone tumor treatments, system-predicted intersonication cooling times were insufficient for nearby tissue to return to body temperature (P = 0.03 in zone 4). DATA CONCLUSION: MRgFUS near bone is susceptible to long tissue decay rates, and unwanted cumulative heating up to 1.2 cm from the surface of the bone. Knowledge of decay rates may be used to alter treatment planning and intraprocedural thermal monitoring protocols to account for prolonged heating by bone. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1526-1533.

Improving thermal dose accuracy in magnetic resonance-guided focused ultrasound surgery: Long-term thermometry using a prior baseline as a reference.

PURPOSE: To investigate thermal dose volume (TDV) and non-perfused volume (NPV) of magnetic resonance-guided focused ultrasound (MRgFUS) treatments in patients with soft tissue tumors, and describe a method for MR thermal dosimetry using a baseline reference. MATERIALS AND METHODS: Agreement between TDV and immediate post treatment NPV was evaluated from MRgFUS treatments of five patients with biopsy-proven desmoid tumors. Thermometry data (gradient echo, 3T) were analyzed over the entire course of the treatments to discern temperature errors in the standard approach. The technique searches previously acquired baseline images for a match using 2D normalized cross-correlation and a weighted mean of phase difference images. Thermal dose maps and TDVs were recalculated using the matched baseline and compared to NPV. RESULTS: TDV and NPV showed between 47%-91% disagreement, using the standard immediate baseline method for calculating TDV. Long-term thermometry showed a nonlinear local temperature accrual, where peak additional temperature varied between 4-13°C (mean = 7.8°C) across patients. The prior baseline method could be implemented by finding a previously acquired matching baseline 61% ± 8% (mean ± SD) of the time. We found 7%-42% of the disagreement between TDV and NPV was due to errors in thermometry caused by heat accrual. For all patients, the prior baseline method increased the estimated treatment volume and reduced the discrepancies between TDV and NPV (P = 0.023). CONCLUSION: This study presents a mismatch between in-treatment and post treatment efficacy measures. The prior baseline approach accounts for local heating and improves the accuracy of thermal dose-predicted volume.

MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo swine brain.

PURPOSE: To present the use of MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo brain tissue as a planning indicator for MR-guided focused ultrasound (MRgFUS). MATERIALS AND METHODS: Calcifications were implanted in ex vivo swine brain and imaged using SWI, MR-ARFI, and computed tomography (CT). SWI-filtered phase images used 3D gradient recalled echo (GRE) images with a Fourier-based unwrapping algorithm. The MR-ARFI pulse sequence used a 2DFT spin-echo with repeated bipolar encoding gradients in the direction of the longitudinal ultrasound beam. MR-ARFI interrogations scanned a subregion (14 × 10 × 12 mm) of the brain surrounding the calcification. They were combined into a single displacement weighted map, using the sum of squares method. Calcification size estimates were based on image profiles plotted along the ±x and ±z direction, at the full-width half-maximum. RESULTS: Both MR-ARFI and SWI were able to visualize the calcifications. The contrast ratio was 150 for CT, 12 for SWI, and 12 for MR-ARFI. Profile measures were 1.35 × 1.28 mm on CT, 1.24 × 1.73 mm on SWI, and 2.45 × 3.02 mm on MR-ARFI. MR-ARFI displacement showed a linear increase with acoustic power (20-80 W), and also increased with calcification size. CONCLUSION: The use of SWI-filtered phase and MR-ARFI have the potential to provide a clinical indicator of calcification relevance in the planning of a transcranial MRgFUS treatment.

Toward MR-guided high intensity focused ultrasound for presurgical localization: focused ultrasound lesions in cadaveric breast tissue.

PURPOSE: To investigate magnetic resonance image-guided high intensity focused ultrasound (MR-HIFU) as a surgical guide for nonpalpable breast tumors by assessing the palpability of MR-HIFU-created lesions in ex vivo cadaveric breast tissue. MATERIALS AND METHODS: MR-HIFU ablations spaced 5 mm apart were made in 18 locations using the ExAblate2000 system. Ablations formed a square perimeter in mixed adipose and fibroglandular tissue. Ablation was monitored using T1-weighted fast spin echo images. MR-acoustic radiation force impulse (MR-ARFI) was used to remotely palpate each ablation location, measuring tissue displacement before and after thermal sonications. Displacement profiles centered at each ablation spot were plotted for comparison. The cadaveric breast was manually palpated to assess stiffness of ablated lesions and dissected for gross examination. This study was repeated on three cadaveric breasts. RESULTS: MR-ARFI showed a collective postablation reduction in peak displacement of 54.8% ([4.41 ± 1.48] µm pre, [1.99 ± 0.82] µm post), and shear wave velocity increase of 65.5% ([10.69 ± 1.60] mm pre, [16.33 ± 3.10] mm post), suggesting tissue became stiffer after the ablation. Manual palpation and dissection of the breast showed increased palpability, a darkening of ablation perimeter, and individual ablations were visible in mixed adipose/fibroglandular tissue. CONCLUSION: The results of this preliminary study show MR-HIFU has the ability to create palpable lesions in ex vivo cadaveric breast tissue, and may potentially be used to preoperatively localize nonpalpable breast tumors.