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To describe the preliminary safety and accuracy of a magnetic resonance (MR) imaging– guided high-intensity–focused ultrasound (HIFU) system employing new technical developments, including ablation control via volumetric thermal feedback, for the treatment of uterine leiomyomata with histopathologic correlation.
In this phase I clinical trial, 11 women underwent MR-guided HIFU ablation (Sonalleve 1.5T; Philips Medical Systems, Vantaa, Finland), followed by hysterectomy within 30 days. Adverse events, imaging findings, and pathologic confirmation of ablation were assessed. The relationship between MR imaging findings, thermal dose estimates, and pathology and HIFU spatial accuracy were assessed using Bland-Altman analyses and intraclass correlations.
There were 12 leiomyomata treated. No serious adverse events were observed. Two subjects decided against having hysterectomy and withdrew from the study before surgery. Of 11 women, 9 underwent hysterectomy; all leiomyomata demonstrated treatment in the expected location. A mean ablation volume of 6.92 cm3 ± 10.7 was observed at histopathologic examination. No significant differences between MR imaging nonperfused volumes, thermal dose estimates, and histopathology ablation volumes were observed (P > .05). Mean misregistration values perpendicular to the ultrasound beam axis were 0.8 mm ± 1.2 in feet-head direction and 0.1 mm ± 1.0 in and left-right direction and −0.7 mm ± 3.1 along the axis.
Safe, accurate ablation of uterine leiomyomata was achieved with an MR-guided HIFU system with novel treatment monitoring capabilities, including ablation control via volumetric thermal feedback.
At the present time, the magnetic resonance (MR) imaging–guided high-intensity–focused ultrasound (HIFU) system approved for clinical use in the United States combines an MR-compatible ultrasound transducer delivering therapy via point-by-point sonication with real-time MR imaging that enables treatment planning and temperature monitoring at treatment sites based on proton-resonance frequency shift MR thermometry (ExAblate 2000, Insightec, Ltd, Tirat Carmel, Israel) (1). This system has been used primarily for ablation of symptomatic uterine leiomyomata, as originally described by Tempany et al (1), and has the potential to offer effective, noninvasive treatment. This therapy remains relatively new, however, with recently reported outcomes data describing symptom relief for at least 12 months; as a result, it is not yet broadly reimbursed in the United States (2). In addition to leiomyoma therapy, MR-guided HIFU ablation shows promise for oncology applications, and it is currently under investigation worldwide for noninvasive treatment of liver, bone, and breast tumors in selected patients (3–7).
As clinical experience with MR-guided HIFU ablation has increased, technical limitations of existing MR-guided HIFU platforms have emerged. The small size of individual focal points used in point-by-point sonication result in long treatment times to ablate large leiomyomata because heating and cooling cycles are required at each focal point. This method may also leave untreated viable tissue between adjacent ablation points (8,9). One sonication strategy developed to address this limitation involves electronic steering of the ultrasound focus along predefined trajectories that enable rapid volumetric sonications by taking advantage of heat diffusion. This approach is made possible with phased-array transducers and driving electronics that enable rapid temporal switching of the focal point location within the treated tissue (9 –13). Existing MR-guided HIFU platforms may also result in either overtreatment or undertreatment of target tissue. This problem has been attributed to several as yet poorly quantified tissue-specific parameters such as ultrasound attenuation and tissue perfusion that lead to treatment inefficiencies and variability in treatment outcome (8,9,14). Incorporating real-time MR thermometry data into thermal feedback algorithms allows for modification of sonication parameters during therapy, resulting in a spatiotemporally controlled temperature profile that has been demonstrated in phantoms and in vivo (9,15–19). Temperature monitoring in the anatomic near and far field may also enhance safety of MR-guided HIFU. Collectively, these recent technical developments may improve safety and treatment monitoring during MR-guided HIFU therapy (9,13).
A new MR-guided HIFU platform (Sonalleve MR-HIFU fibroid therapy system; Philips Medical Systems, Vantaa, Finland) employs several of these treatment monitoring capabilities, including MR thermometry monitoring of the anatomic target region comprising the near and far field and ablation control via volumetric thermal feedback. More recent studies have provided information concerning the safety and feasibility of this MR-guided HIFU platform for uterine leiomyomata. Voogt et al (20) prospectively evaluated the technical feasibility of this system and compared MR imaging nonperfused volumes with MR-guided HIFU thermal dose estimates. Kim et al (21,22) suggested a relationship between treatment cell size, energy efficiency, and ablation volume with this same platform and correlated dynamic contrast-enhanced MR imaging parameters with MR-guided HIFU thermal dose estimates. These studies do not correlate imaging findings to histopathologic outcome, and they do not describe analyses concerning the spatial accuracy of this system. The purpose of this clinical study was to assess both the preliminary safety and the targeting accuracy of this MR-guided HIFU platform for the treatment of uterine leiomyomata, including imaging-to-histopathologic correlations of ablation outcome.
This dual-center, single-arm, prospective study (NCT00837161) was approved by the institutional review boards of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, and St. Luke’s Episcopal Hospital, Houston, Texas. All patients provided written informed consent. Eligible patients were healthy women (30–59 years old) who were either premenopausal or perimenopausal (follicle-stimulating hormone < 40 mIU/mL). Eligible patients had a fibroid uterus with a uterine size of < 24 weeks of pregnancy. All patients reported severe symptoms attributed to leiomyomata, with leiomyoma size and symptom severity resulting in recommendations for abdominal hysterectomy (23). Symptom severity was assessed by the Uterine Fibroid Symptom Quality-of-Life Questionnaire with a score ≥ 50 necessary for enrollment (24). Targeted leiomyomata were 2–16 cm in diameter and were intramural, nonpedunculated subserosal or submucosal < 5 cm. Hysterectomy was performed 3–30 days after MR-guided HIFU. Pregnant women and women with standard MR imaging contraindications were excluded.
Patients in this study were 39–55 years old (mean, 46 years old), and all patients had completed childbearing (Table 1). Patients had a mean uterine volume of 1,084.7 cm3 ± 761.9 (range, 377.5–2,490.5 cm3) and a mean targeted leiomyoma volume of 246.7 cm3 ± 356.2 (range, 2.1–1,140 cm3). Of the targeted intramural leiomyomata, 10 were located in either the anterior (n = 8) or the posterior (n = 2) body of the uterus; one leiomyoma was submucosal; and one was subserosal, attached to the anterior body of uterus. Three patients had undergone prior myomectomy. Uterine leiomyoma symptoms included excessive bleeding (n = 10 patients), pain (n = 9), bloating (n = 9), frequent urination (n = 7), and constipation (n = 2).
Components of this clinical MR-guided HIFU system (Sonalleve MR-HIFU fibroid therapy system) include the MR scanner (Achieva 1.5T, Philips Healthcare, Best, the Netherlands), an integrated three-channel pelvic radiofrequency receiver coil with one anterior and two posterior elements, a 256-element phased-array ultrasound transducer, and an electromechanical transducer positioning system.
All subjects underwent three MR imaging examinations: MR imaging performed within 6 weeks before MR-guided HIFU, MR imaging performed during MR-guided HIFU, and MR imaging performed 3–5 days after MR-guided HIFU and before hysterectomy. MR images obtained before treatment defined leiomyoma size, volume, location, and presence of enhancement.
All MR imaging examinations were performed with a clinical 1.5T MR system (Achieva 1.5T). MR imaging examinations included three-dimensional T2-weighted planning images and T1-weighted imaging before and after administration of gadopentetate dimeglumine (dose 0.1 mmol/kg body weight; Magnevist, Berlex Laboratories, Wayne, New Jersey) (Appendix 1; available online at www.jvir.org). MR imaging examinations performed before treatment and during MR-guided HIFU were completed with the patient lying in the prone position and using the dedicated pelvic MR coil. Of 11 patients, 2 also underwent MR imaging after treatment in the prone position using this coil. Nine patients underwent MR imaging after treatment in the supine position using a standard 16-channel torso coil with eight anterior and eight posterior elements (SENSE XL Torso Coil; Philips Healthcare).
MR-guided HIFU ablation was performed with a volumetric sonication technique and controlled via thermal feedback. With volumetric ablation, the HIFU transducer applies continuous acoustic energy along concentric circles using treatment cells 4 mm, 8 mm, or 12 mm in diameter (Fig 1a– b), with cooling times between each ablation. The planned treatment volume (PTV) comprises treatment cells within a targeted area (Appendix 2, a– b; available online at www.jvir.org) (13). Volumetric heating may be performed with or without thermal feedback, termed feedback cells and treatment cells. With feedback cells, each volumetric ablation is programmed to achieve ablative temperatures, with duration of sonication determined by the system and adjusted according to the mean cell temperature. For treatment cells, duration of sonication is fixed for each cell size.
In preparation for treatment, hair from the anterior abdominal wall and pubic region was removed, a Foley catheter was inserted, an intravenous line for administering conscious sedation was placed, and an acoustically transparent gel pad was applied under the pelvic region between the HIFU tabletop and the patient’s skin. Of 11 patients, 10 received conscious sedation with midazolam hydrochloride (mean, 3.5 mg; range, 1– 6 mg) and fentanyl (mean, 187.5 μg; range, 75–325 μg). In 2 of 11 patients, alprazolam (1 mg each) was administered for anxiolysis before the procedure, at the discretion of the treating physician. No bowel motility agents were used. MR imaging before treatment included a three-dimensional T2-weighted sequence to localize the transducer, uterus, and targeted leiomyoma. The presence of air bubbles at the gel pad–skin interface was assessed by a two-dimensional fast-field echo pulse sequence. If bubbles > 1 mm were detected in the anticipated beam path, the gel pad and patient were repositioned followed by an additional two-dimensional fast-field echo pulse sequence to confirm absence of air bubbles (Appendix 1; available online at www.jvir.org).
Using a sagittal three-dimensional T2-weighted turbo spin-echo sequence and the system software, the radiologist outlined the PTV of the leiomyoma. The planned HIFU beam path was superpositioned on the patient’s anatomic imaging to verify a clear acoustic path. Sonication cells with diameters of 4 mm, 8 mm, or 12 mm were used such that the cells fell within the outlined PTV in all planes (Appendix 2, a– b; available online at www.jvir.org). Safety margins included 4 cm between the PTV and patient’s spine or intestine and 1.5 cm to uterine serosa.
A low-power (10 – 40 W) test sonication was performed to verify that heating would occur in the intended location, to correct for any spatial offset from the geometric focus owing to tissue interactions with the HIFU beam, and to determine the power level necessary to achieve therapeutic ablation based on the test sonication power applied and resultant temperature elevation. Low power applied during the test sonication was gradually increased until a mean temperature elevation of 5°C was observed. The treatment cell was exposed to higher power (80 –150 W) therapeutic sonications such that ablative temperatures (> 55°C) and desired thermal dose (> 240 cumulative equivalent minutes at 43°C [CEM43]; see later) were achieved (Fig 2a– d). A 90-second pause, set by system software, allowed tissue cooling between each sonication. Sonications were monitored during therapy, with treatment modified as needed. If women reported symptoms during the procedure, including pain or skin heating, they could press a button to cease treatment. Sonication parameters are presented in Appendix 3 (available online at www.jvir.org).
The MR-guided HIFU graphic user interface displayed real-time two-dimensional temperature data with a color scale overlaid on gray-scale MR anatomic images (Fig 2a– b). The target and adjacent anatomic near and far fields were monitored with real-time MR thermometry. Thermal dose maps were calculated according to the Sapareto-Dewey equation using a linear interpolation of temperature between dynamic acquisitions with a unit of cumulative equivalent minutes at 43°C (CEM43) (14). Preexisting data suggest that 30 cumulative equivalent minutes at 43°C (30 CEM43) may correspond to the onset of tissue thermal injury, whereas 240 cumulative equivalent minutes at 43°C (240 CEM43) reflects complete necrosis in most tissues (14). Temperature images were acquired for at least 2 minutes after sonication to enable assessment of accumulated thermal dose during cooling. Temperature standard deviation estimates were used for dose compensation and updated according to the signal-to-noise ratio of the acquired image (13). Thermal dose estimates of both 30 CEM43 and 240 CEM43 were displayed during and after each sonication (Fig 2c– d).
At site 1 (NIH Clinical Center), all patients (n = 9) were admitted overnight. At site 2 (St. Luke’s Episcopal Hospital), patients (n = 2) were discharged the same day. Patients were contacted by phone at 24 hours, 48 hours, 1 week, and 2 weeks after therapy to assess symptoms and adverse events before hysterectomy. They returned for a follow-up clinic visit and MR imaging 3–5 days after therapy.
MR imaging scans obtained before and after treatment were analyzed by two independent readers who were informed of the targeted region but were unaware of the PTV (Oulu University Hospital, Oulu, Finland, and Factory CRO, Bilthoven, the Netherlands). MR imaging analysis was performed with either OsiriX imaging software (Pixmeo, Geneva, Switzerland) or ViewForum software (Philips Healthcare). See Appendix 4 (available online at www.jvir.org) for additional details concerning assessment of leiomyoma ablation volumes and HIFU spatial accuracy.
The abdominal cavity and uterine surface were inspected at surgery for unintended thermal damage. Given the large uterine size and other untreated leiomyomata, MR images were examined alongside hysterectomy specimens to facilitate identification of treated leiomyomata (Fig 2e– g).
Hysterectomy specimens were inspected by the pathologist for unintended damage. After gross examination, specimens were bivalved to expose the endometrial cavity and cut at 0.5-cm intervals in the uterine sagittal plane. Cut uterine surfaces were examined grossly for leiomyomata and for pathologic findings representing treatment using hematoxylin and eosin staining (Fig 2g–j). Treated areas were measured for their largest orthogonal dimensions in the planar cut surface with the third dimension estimated by summing the affected 0.5-cm-thick sagittal planes. HIFU ablation volumes were calculated using the prolate ellipsoid volume formula. After all targeted tumors were grossly identified and measured, specimens were fixed in formalin. Representative samples of serosa, myometrium, and endometrium in the treated path and remote from the treated volume were evaluated for histopathologic abnormalities including necrosis, hemorrhage, or fibrosis.
Demographic, study population characteristics, treatment parameters, and adverse events were described using frequency distributions or simple descriptive statistics. Differences between the calculated contour and ellipsoid ablation volumes were assessed using a paired t-test, and their agreement was assessed using Bland-Altman analysis. If mean contour and ellipsoid values were not observed to be different, subsequent comparisons were performed between contour values, HIFU thermal dose estimates, and histopathology volumes.
Differences between the contour MR imaging measurements, 30 CEM43 and 240 CEM43 thermal dose estimates, and histopathology ablation volumes were assessed using paired t-tests; pair-wise agreements were assessed using Bland-Altman analyses. Intraclass correlation coefficients were used to assess the overall level of agreement among MR imaging volumes, thermal dose estimates, and histopathology considered together. Data were reported as mean ± standard deviation and were analyzed using SAS version 9.2 (SAS Institute, Inc, Cary, North Carolina). All P values < .05 were considered statistically significant.
There were 12 leiomyomata treated in 11 patients. In the 11th patient treated, two leiomyomata were treated during one MR-guided HIFU treatment session. Average treatment session duration, defined as from the time the patient was positioned on the HIFU table until transport to the recovery room, was 3.67 hours ± 0.7 (range, 2.67–5.55 h). Preplanning time, defined as the time from when the patient was placed on the table to the first survey scan, was 13.2 minutes ± 5.4 (range, 8 –28 min). The planning time, defined as the time from the first survey scan to delivery of the first sonication, was 104.4 minutes ± 49.2 (range, 48 –241 min). The sonication time, defined as the time from the first sonication to the last sonication, was 54.6 minutes ± 18.0 (range, 23– 86 min). The posttreatment duration, defined as the time from performance of the last sonication to transferring the patient off the HIFU table, was 34.2 minutes ± 12.0 (range, 12– 60 min). The duration of time for transfer of the patient to the recovery area, subsequent to removal off the HIFU tabletop, was 13.2 minutes ± 9.6 (range, 1–16 min).
Of 11 patients, 9 underwent hysterectomy, with a mean time of 9 days between MR-guided HIFU and hysterectomy (range, 3–20 d); 2 patients decided against having hysterectomy citing that the postoperative recovery would interfere with their work schedule and withdrew from the study before surgery. Nontarget thermal injury was not observed on contrast-enhanced MR images obtained after treatment, during surgical inspection at hysterectomy, or at gross pathology assessment. At gross pathology assessment, all leiomyomata showed confluent treatment in the expected location. In eight of nine cases, confluent treatment in the expected location was confirmed at histopathologic assessment with hematoxylin and eosin staining. In one of these eight cases, one patient had an additional 0.8-cm focus of hemorrhagic necrosis within uterine myometrium adjacent to a 2-cm submucosal leiomyoma that moved during treatment. This movement was observed on MR imaging during treatment; concurrently, the patient experienced pain and pressed the emergency button, interrupting treatment after 24.4 seconds of sonication. A ninth patient underwent MR-guided HIFU of a small area within an 11-cm leiomyoma containing extensive myxomatous degeneration. Although identified by needle localization on gross pathology, the area treated by HIFU at histopathology was difficult to identify, being in close proximity to the area of preexisting necrosis. Table 2 delineates ablation volumes determined by MR imaging assessment using the contour method, 30 CEM43 and 240 CEM43 thermal dose estimates, and histopathologic findings for each patient. The histopathologically confirmed mean ablation volume was 6.92 cm3 ± 10.7 with a mean targeted leiomyoma volume of 246.7 cm3 ± 375.8. These intentionally small volumes of treatment were in keeping with the study goal, which was to treat enough tissue to allow comparisons between MR imaging findings and pathology.
Complications during and after HIFU were described using the Society of Interventional Radiology Classification System for Complications by outcome (25). During and after HIFU, no major complications were reported. Of the minor complications reported, transient abdominal cramping (n = 9) or leg pain (n = 2) were the most frequently reported. These expected minor adverse events were self-limited, resolving by 72 hours in all cases. Specifically, no skin burns or nerve injuries were observed. One patient with chronic constipation had blood in the stool in the recovery area after HIFU treatment. This adverse event was reported to be a relatively common occurrence for this patient, and was not attributed to HIFU treatment. Another patient who developed transient suprapubic pain and urinary frequency 1 week after HIFU treatment had negative urinalysis and culture; physical assessment did not reveal any findings. The patient was prescribed ibuprofen to relieve the pain symptoms. The beam path was not near the symptomatic area, and these symptoms were attributed to Foley catheterization.
MR-guided HIFU spatial targeting was assessed by comparing intended and actual treated locations and calculating misregistration values. Test sonications were discarded from misregistration analyses because they were used to calibrate spatial targeting. Mean misregistration perpendicular to the ultrasound beam axis was 0.8 mm ± 1.2 (range, −2.6 to +3.7 mm) from the planned location in the feet-head direction and 0.1 mm ± 1.0 (range, −4.9 to +1.7 mm) from the planned location in the left-right direction. Misregistration along the beam axis was −0.7 mm ± 3.1 from the planned location (range, −8.5 to +6.2 mm).
Mean contour and ellipsoid measured volumes were equivalent and in agreement by Bland-Altman analysis (P > .05) enabling subsequent comparisons to be performed using only contour volumes. Mean contour MR imaging ablation volumes were not different from histopathology ablation volumes (P = .5348) and were in agreement with histopathology ablation volumes by Bland-Altman analysis (P = .5345).
Paired comparisons between contour MR imaging ablation volumes and 30 CEM43 thermal dose estimates indicated no significant difference between the mean values of these data (P = .5510). Contour MR imaging ablation volumes and 30 CEM43 values showed agreement by Bland-Altman analysis (P = .5500), showing small magnitudes of differences within tight thresholds (Appendix 5, a; available online at www.jvir.org). However, contour MR imaging volumes were significantly different from the smaller 240 CEM43 thermal dose estimates (P = .03) and did not show agreement with the smaller 240 CEM43 thermal dose estimates (P = .0328) (Appendix 5, b; available online at www.jvir.org), suggesting that 30 CEM43 may provide a more accurate description of the treatment volume. Comparisons between histopathology ablation volumes and the 30 CEM43 and 240 CEM43 thermal dose estimates indicated no difference between the mean values of these data (P = .93 and P = .33). Agreement between histopathology ablation volumes and the 30 CEM43 and 240 CEM43 thermal dose estimates was observed via Bland-Altman analysis (P > .05) and could be visually noted by the tight thresholds and small mean differences with minimal data falling outside the thresholds (Appendix 5, c and d; available online at www.jvir.org). Considered together, the MR imaging, thermal dose, and histopathology measurements showed agreement (intraclass correlation coefficient = 0.6996).
We describe the preliminary safety and accuracy of a novel MR imaging– guided HIFU system employing volumetric feedback ablation for the treatment of uterine leiomyomata, with histopathologic correlation. All patients in this study tolerated the MR-guided HIFU procedure well, with no serious adverse events. Confluent zones of treatment were observed in all cases except one for which it was difficult to localize a small ablation zone adjacent to a large, partially necrotic leiomyoma. Agreement was observed between ablation volumes estimated via patients’ MR-guided HIFU thermal dose estimates obtained during the procedure and contrast-enhanced MR images and histopathology obtained after treatment, including hysterectomies performed several weeks after HIFU. These findings suggest accurate and predictable thermoablation may be achieved with this MR-guided HIFU system.
Existing MR-guided HIFU platforms have demonstrated safety, feasibility and effectiveness for ablation of leiomyomata, with short-term follow-up. Variation in treatment temperatures, leading to both overtreatment and undertreatment of target tissue, previously limited the accuracy of MR-guided HIFU (9). Controlling ablation by use of real-time thermometry data provided by thermal feedback may prevent tissue overtreatment and undertreatment (9). Representative cases using 8-mm and 12-mm volumetric feedback and treatment cells suggest greater ability to achieve the desired range of ablative temperatures (60°–62°C) and greater temperature control with feedback compared with more traditional treatment cell sonications (Fig 3a– b). Use of volumetric feedback ablation also has the potential for superior energy efficiency compared with point-by-point ablations (13,21). Depending on treatment cell size and power used, the volume ablated per sonication time with the device in this study was 0.12–7.50 cc/min, which would be of interest to assess in future clinical studies.
There are limitations to this study, which was a “proof-of-concept” study with a small number of patients. Similar to Tempany et al (1), by performing a hysterectomy soon after treatment, we were unable to correlate treatment with change in symptoms. Because our study goal was to treat enough tissue to allow comparisons between MR imaging findings and pathology, we did not treat large volumes within each leiomyoma. Several challenges arose because of the small treated leiomyoma volumes. Strategies developed to identify treated areas on gross pathology included review of the MR images by the radiologist, gynecologist, and pathologist and MR imaging– guided needle localization of the HIFU-treated area within the uterine specimen before histopathologic assessment. There are also inherent uncertainties comparing histopathology and MR imaging treatment volumes because of the challenges associated with accurately matching imaging to gross pathology planes, the observed increase in leiomyoma volume when leiomyomata were transected at pathology, and an estimated three-dimensional measurement, orthogonal to the cut surface plane at 5-mm intervals. The modest volumes of ablation achieved with an average treatment session duration of 3.75 hours during this phase I trial are not reflective of future treatment times and achievable ablation volumes. In the next prospective trial with this device, MR-guided HIFU will be used as the primary treatment, with the goal of achieving larger, therapeutic ablation volumes, and patients’ symptoms will be followed as a measure of treatment effect.
In conclusion, in this preliminary study, safe and accurate ablation of uterine leiomyomata was achieved using an MR-guided HIFU device employing temperature monitoring of the target and anatomic near and far fields and volumetric ablation control via thermal feedback, with histopathologic confirmations of treatment outcome. Volumetric MR-guided HIFU ablation with these treatment monitoring capabilities may facilitate predictable, rapid, and confluent thermoablation of benign and malignant neoplasms.
This work was supported in part by the NIH Center for Interventional Oncology, NIH Intramural Research Training Program, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, by the NIH Clinical Center via a Cooperative Research and Development Agreement (CRADA) between NIH and Philips Healthcare, and by the National Cancer Institute under Contract No. HHSN261200800001E.
The authors thank Sandra McKee, RT (R)-(MR), for her dedication to the patient care and MR imaging acquisition necessary for successful completion of this clinical trial. The authors extend special thanks to Marcy Maguire, MD, for her assistance at hysterectomy and perioperative care. The authors also thank Stacey Gates, RN, Debra Dees, RN, and Brenda Lambert, RN, who were instrumental in patient recruitment and data management, and Julia Locklin, RN, MSc, for her assistance with chart review. The authors also extend special thanks to Professor Roberto Blanco, MD, for MR imaging volume readings and to Teuvo Vaara, DSc, Jouko Soini, PhD, and Minna Seppälä, MSc (Eng), for their assistance in data analysis. A subset of the study’s statistical analyses was conducted by TechnoStat Inc. (Raanana, Israel).
A.P., S.S., and H.J.N. are salaried employees of Philips Healthcare. Philips has market interest and intellectual property in this field. B.J.W. has NIH Intramural Research funding Z01/ZIA #CL04040011-03.
Ablation volumes of leiomyomata were measured in two ways:
Measurements obtained via each method from each reader were averaged to obtain final measurements of leiomyoma volume and ablation volume for each target.
A custom-made semiautomated measurement tool (Philips Medical Systems, Vantaa, Finland) was developed using software interface description language (IDL version 6.1; ITT Visual Information Solutions, Boulder, Colorado) to assess high-intensity–focused ultrasound (HIFU) spatial targeting accuracy. This measurement tool calculated the center of mass of temperature elevation in the target region and compared the intended sonication location from the HIFU planning software with the actual treatment location indicated as the thermal dose center of mass estimates at the end of the treatment session. Misregistration was defined as the distance between the center of mass and the intended location.
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None of the other authors have identified a conflict of interest.