MR-guided Focused Ultrasound Treatment Research Articles

CTNI-76. A PHASE 1/2 DOSE ESCALATION AND EXPANSION STUDY OF SONODYNAMIC THERAPY WITH SONALA-001 IN COMBINATION WITH NON-ABLATIVE MR-GUIDED FOCUSED ULTRASOUND IN SUBJECTS WITH PROGRESSIVE OR RECURRENT GLIOBLASTOMA

Abstract Recurrent glioblastoma (rGBM) is a lethal brain tumor with no effective standard of care option and an extremely poor prognosis (median survival 6 to 8 months after first recurrence). Sonodynamic therapy (SDT) is a non-invasive combination therapy that utilizes a drug, aminolevulinic acid HCL (SONALA-001, ALA), and a device, the Exablate 4000 Type 2.0 to deliver MR-guided focused ultrasound (MRgFUS). Preclinical studies have shown that SDT activates protoporphyrin IX (PpIX) to generate reactive oxygen species that lead to tumor cell death and improved survival in animal glioma models. A first-in-human Phase 0 trial (NCT04559685) indicated that ALA SDT was well-tolerated and not associated with off-target cellular or radiographic effects and provided direct evidence of reactive oxygen species formation and targeted tumor cell death in recurrent high-grade glioma (rHGG). SDT-202 is a Phase 1/2 multicenter, open-label, dose escalation and expansion study (NCT05370508) of iv SONALA-001 (ALA) in combination with MRgFUS for SDT in patients with progressive or recurrent GBM. Dose escalation will include an initial drug and energy dose escalation of ALA SDT utilizing an accelerated titration design with single subject cohorts for dose level cohorts 1 and 2, followed by cohort 3 with 3 + 3 design for additional dose escalation. SONALA-001 is administered 6 to 9 hours prior to MRgFUS treatment. Once the RP2D is determined, Phase 2 dose expansion will enroll approximately 36 additional subjects to assess safety and efficacy of repeated cycles of ALA SDT at the optimized RP2D. Endpoints of this study are safety evaluation, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and determination of pharmacokinetic (PK) parameters. The Phase 2 portion will further characterize safety of RP2D along with evaluation of efficacy with PFS6 (mRANO), ORR, CBR, DOR, DOCR, TTR, and OS. Preliminary PK and safety results will be presented.

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up

Background MR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined. Objective To assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET. Methods 14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24-month data. Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores. Results The mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p < 0.001) whilst BFS-NTA worsened by 8.8% (p < 0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p < 0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p < 0.001) reduction from post anterior-VIM/VOP to post-PSA ablation. Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p < 0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p = 0.001) and non-treated arm (UETTS-NTA) 30.5% (p = 0.003). At 24 months residual adverse effects were slight unsteadiness (n = 1) and mild hemi-chorea (n = 1). Conclusion Unilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile.

Learning Multiparametric Biomarkers for Assessing MR-Guided Focused Ultrasound Treatment of Malignant Tumors.

Noninvasive MR-guided focused ultrasound (MRgFUS) treatments are promising alternatives to the surgical removal of malignant tumors. A significant challenge is assessing the viability of treated tissue during and immediately after MRgFUS procedures. Current clinical assessment uses the nonperfused volume (NPV) biomarker immediately after treatment from contrast-enhanced MRI. The NPV has variable accuracy, and the use of contrast agent prevents continuing MRgFUS treatment if tumor coverage is inadequate. This work presents a novel, noncontrast, learned multiparametric MR biomarker that can be used during treatment for intratreatment assessment, validated in a VX2 rabbit tumor model. A deep convolutional neural network was trained on noncontrast multiparametric MR images using the NPV biomarker from follow-up MR imaging (3-5 days after MRgFUS treatment) as the accurate label of nonviable tissue. A novel volume-conserving registration algorithm yielded a voxel-wise correlation between treatment and follow-up NPV, providing a rigorous validation of the biomarker. The learned noncontrast multiparametric MR biomarker predicted the follow-up NPV with an average DICE coefficient of 0.71, substantially outperforming the current clinical standard (DICE coefficient = 0.53). Noncontrast multiparametric MR imaging integrated with a deep convolutional neural network provides a more accurate prediction of MRgFUS treatment outcome than current contrast-based techniques.

2149 Long Term Outcome of Mr Guided Focused Ultrasound Treatment and Laparoscopic Myomectomy for Symptomatic Uterine Fibroids

Study Objective To compare the long-term outcome of laparoscopic myomectomy with MR-guided focused ultrasound (MRgFUS) for symptomatic uterine fibroids. Design A cohort study, from January 2012 to January 2017. Setting Single tertiary care center. Patients or Participants All patients with symptomatic uterine fibroids treated operatively with laparoscopic myomectomy or treated conservatively with MR-guided focused ultrasound. Interventions A telephone interview was performed to assess further interventions and sustained fibroid associated symptoms using the Uterine Fibroid Symptom and Quality of Life symptom severity score (UFS-QOL-SSS). Measurements and Main Results One-hundred fifty-four women met the inclusion criteria. Complete follow-up was achieved for 64 women underwent laparoscopic myomectomy and 68 were treated by MRgFUS. Follow up time was similar for both groups (median, IQR: 31 month, (17-51) vs 36 month (24 - 41); P=0.95, respectively). The rate of additional interventions was 5 (7.8%) and 9 (13.2%), respectively (p=0.312). Similarly, the uterine fibroid symptom-quality of life-symptom severity score (QOL-SSS) questionnaire at follow up interview revealed comparable score 17(12-21) vs 17 (13-22) for laparoscopic myomectomy and MRgFUS, respectively (p=0.439). Analyzing each of the symptoms separately (bleeding, changes in menstruation, abdominal pain, bladder activity, nocturia, fatigue), did not change these findings. Conclusion Long term outcome and surgical intervention following MRgFUS treatment for uterine fibroids seems comparable with that laparoscopic myomectomy. Further larger randomized trials are needed to confirm these findings.

The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound.

Transcranial MR-guided focused ultrasound (MRgFUS) is a minimally invasive treatment for movement disorders. Considerable interpatient variability in skull transmission efficiency exists with the current clinical devices, which is thought to be dependent on each patient's specific skull morphology. Lower skull density ratio (SDR) values are thought to impede acoustic energy transmission across the skull, attenuating or preventing the therapeutic benefits of MRgFUS. Patients with SDR values below 0.4 have traditionally been deemed poor candidates for MRgFUS. Although considerable anecdotal evidence has suggested that SDR is a reliable determinant of procedural and clinical success, relationships between SDR and clinical outcomes have yet to be formally investigated. Moreover, as transcranial MRgFUS is becoming an increasingly widespread procedure, knowledge of SDR distribution in the general population may enable improved preoperative counseling and preparedness. A total of 98 patients who underwent MRgFUS thalamotomy at the authors' institutions between 2012 and 2018 were analyzed (cohort 1). The authors retrospectively assessed the relationships between SDR and various clinical outcomes, including tremor improvement and adverse effects, as well as procedural factors such as sonication parameters. An SDR was also prospectively obtained in 163 random emergency department patients who required a head CT scan for various clinical indications (cohort 2). Patients' age and sex were used to explore relationships with SDR. In the MRgFUS treatment group, 17 patients with a thalamotomy lesion had an SDR below 0.4. Patients with lower SDRs required more sonication energy; however, their low SDR did not influence their clinical outcomes. In the emergency department patient group, about one-third of the patients had a low SDR (< 0.4). SDR did not correlate with age or sex. Although lower SDR values correlated with higher energy requirements during MRgFUS thalamotomy, within the range of this study population, the SDR did not appreciably impact or provide the ability to predict the resulting clinical outcomes. Sampling of the general population suggests that age and sex have no relationship with SDR. Other variables, such as local variances in bone density, should also be carefully reviewed to build a comprehensive appraisal of a patient's suitability for MRgFUS treatment.

MRI predictors of clinical success in MR-guided focused ultrasound (MRgFUS) treatments of uterine fibroids: results from a single center

To assess the technical and clinical results of MRgFUS treatment and factors affecting clinical treatment success.

MRI predictors of clinical success in MR-guided focused ultrasound (MRgFUS) treatments of uterine fibroids: results from a single centre.

To assess the technical and clinical results of MRgFUS treatment and factors affecting clinical treatment success. A total of 252 women (mean age, 42.1 ± 6.9 years) with uterine fibroids underwent MRgFUS. All patients underwent MRI before treatment. Results were evaluated with respect to post-treatment nonperfused volume (NPV), symptom severity score (SSS), reintervention rate, pregnancy and safety data. NPV ratio was significantly higher in fibroids characterized by low signal intensity in contrast-enhanced T1-weighted fat saturated MR images and in fibroids distant from the spine (>3 cm). NPV ratio was lower in fibroids with septations, with subserosal component and in skin-distant fibroids (p < 0.001). NPV ratio was highly correlated with clinical success: NPV of more than 80 % resulted in clinical success in more than 80 % of patients. Reintervention rate was 12.7 % (mean follow-up time, 19.4 ± 8 months; range, 3-38). Expulsion of fibroids (21 %) was significantly correlated with a high clinical success rate. No severe adverse events were reported. Adequate patient selection and correct treatment techniques, based on the learning curve of this technology, combined with technical advances of the system, lead to higher clinical success rates with low complications rate, comparable to other uterine-sparing treatment options. • MRgFUS appears to be a valid alternative to other uterus-preserving therapies • Patient selection is a significant factor in achieving high NPV ratios • MRI screening parameters correlate with the amount of fibroid ablation in MRgFUS • NPV results of more than 80 % correlate with higher clinical success rates.

SU‐E‐J‐162: Quality Assurance Procedures for MR Guided Focused Ultrasound Treatment of Bone Metastasis

Purpose:The purpose of this work is to develop and verify our quality assurance (QA) procedures to ensure the safety and efficacy of MR‐guided focused ultrasound (MRgFUS) treatment of bone metastases.Methods:A practical QA program was developed. Monthly and daily QA (DQA) procedures were performed. The major QA items included the checks of the machine hardware, software and patient safety features. Briefly, these checks/tests include: 1) the cooling system reservoir and treatment table; 2) power to the treatment table; 3) the MR coil; 4) the transducer position with MRI; 5) image display on the treatment work station; 6) the effective focal spot in 3 directions using MR thermometry; and 7) all the safety devices including a sonication lamp, and the emergency stop‐sonication switches. In order to avoid patient skin burn, it is important to remove gas bubbles in the interfaces between the treatment table and the gel pad, and the gel pad and patients skin during the patient setup. Our QA procedures have been verified and evaluated through patient treatments. Seven patients with scapula, humeral head, sacrum, ilium, pubic ramus and acetabular bone metastases were treated using MRgFUS.Results:Our study showed that all seven patients tolerated the MRgFUS treatment well. No skin toxicity or other complications were observed. The pain score (0–10) using the visual analog scale (VAS) was significantly reduced from 8.0 ± 1.1 before treatment to 4.7 ± 3.0, 3.0 ± 1.5, 3.2 ± 2.8 and 3.4 ± 1.5 at one day, one month, two months and three months after the MRgFUS treatment, respectively.Conclusion:We demonstrated that with the appropriate QA procedures, MRgFUS is a safe, effective and noninvasive treatment modality for palliation of bone metastases.

MR-guided focused ultrasound (MRgFUS) is effective for the distinct pattern of uterine fibroids seen in African-American women: data from phase III/IV, non-randomized, multicenter clinical trials.

BackgroundUterine fibroids are common among women at the reproductive age. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel and a conservative treatment for symptomatic cases. The aim of the study was to evaluate the efficacy of MRgFUS in African-American (AA) women compared with that in non-African-Americans (non-AA).MethodsA single-armed phase IV study was conducted to establish the efficacy of treatment in AA women. Comparison of patient, fibroid, and treatment characteristics from this trial was compared with that of the previously published phase III trial. Both studies were approved by the IRB of each medical center.ResultsSixty-three AA and 59 non-AA women were treated with MRgFUS. Although AA women had a different pattern of disease, outcomes were similar in both groups. AA patients had a significant higher total number of fibroids compared with non-AA (median 6.0, interquartile range (IQR) 3.0–10.0 vs. 2.0, IQR 1.0–4.0, respectively, p < 0.001), although their total fibroid volume was significantly smaller (median 196.9 cm3, IQR 112.8–415.3 cm3 vs. 394.8 cm3, IQR 189.8–674.4 cm3, respectively, p < 0.001). AA women were younger compared with non-AA (mean ± SD 43.4 ± 5.1 vs. 46.3 ± 4.1 years of age, respectively, p = 0.001) when they presented for treatment. The rate of alternative treatments as well as fibroid-associated symptoms at follow-up time points (3, 6, 12, 24, and 36 months, period following MRgFUS treatment) did not differ according to race (p ≥ 0.62).ConclusionDespite differences in the pattern of fibroid disease, MRgFUS for uterine fibroids has a similar efficacy for AA women compared with non-AA women.

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

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).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.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.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.

MR-guided focused ultrasound for the novel and innovative management of osteoarthritic knee pain

BackgroundSevere knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy.MethodsEight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment.ResultsSix patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p?<?0.0001). There were no adverse side effects or complications during and after treatment.ConclusionsThese initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA.Trial registrationTrial Registration: UMIN000010193

Safety and quality assurance of MR-guided focused ultrasound (MRgFUS) in palliation of painful bone metastases.

9565 Background: Palliation of bone metastases is typically performed with radiation therapy (RT). However, a significant minority of patients cannot obtain durable relief from RT. MRgFUS combines non-invasive focused ultrasound with MR guidance. Preliminary phase III results comparing MRgFUS to sham treatment have demonstrated efficacy. This study examines the safety of this procedure in a large prospective, multi-center study. Methods: Patients with a painful bone metastasis were randomized (3:1) to either MRgFUS or sham treatment for the single most painful lesion. Sham patients were given the opportunity to cross over after 2 weeks. Each adverse event (AE) was recorded prospectively and scored for severity and relation to treatment. Results: Thirty-seven patients were enrolled to receive sham treatment and 115 to receive MRgFUS. Sites of treatment were: 102 pelvis, 28 thorax, 7 lower extremity and 2 upper extremity. Seventy-seven target lesions were osteolytic, 29 were osteoblastic and 33 were mixed. Treatment was discontinued prior to completion in 8 treatments. Of these, 7 were pelvic targets and 6 lesions were osteolytic. The most common reasons for discontinuation were pain (4) and patient movement (2). Forty-seven percent of treatment patients and 2.7% of sham patients reported at least one AE. Of 76 AEs, 67 were considered non-significant and anticipated, 57 being intra-procedure pain. Four significant events included 2 possibly related fractures at treated lytic lesion sites, 1 grade 3 skin burn and 1 patient with neuropathy. Four patients experienced events unrelated to study treatment and 1 patient experienced temporary apnea from anesthesia described as incidental. Conclusions: MRgFUS is a safe treatment for palliation of painful bone metastases. Ninety-three percent of MRgFUS treatments were carried out to completion. Three percent of patients experienced significant AEs, including 2 fractures of treated lytic tumors. These safety data reinforce and confirm previous experience with this technology and encourage its use for patients not suitable for RT. Clinical trial information: NCT00656305.

TH-E-BRA-03: Clinical Experience at Fox Chase Cancer Center for Treatment of Bone Metastases Using ExAblate 2000 with MR Guidance

Purpose: To evaluate the safety and efficacy of MR guided focused ultrasound (MRgFUS) treatment for bone metastases. Methods: Six patients with scapula (2), humeral head, sacrum, ilium and pubic ramus bone metastases were treated using ExAblate 2000 under MR guidance. In addition to the monthly and annual quality assurance (QA), pre-treatment machine calibration was performed before each treatment including the functionality of the treatment software and the mechanical motion control systems. The effective ultrasound focal spot was verified with an acoustic phantom using MR thermometry. The patient was positioned on a gel pad. The interface between the treatment table, the gel pad and the patient was immersed in degassed water for acoustic coupling. Caution was taken to remove all gas bubbles between the interfaces. Treatment was performed under conscious sedation. Six to eighteen sonications were delivered for each patient treatment depending on each lesion's size. Patients were treated with a frequency of 1 MHz; 32 ± 4.0 to 96 ±11W acoustic power and 628 ± 78 to1859 ± 338J energy for 20–30s for each sonication. MR phase images were used to monitor the temperature changes in real-time. Based on the temperature feedback, the acoustic power was adjusted to reach designed temperatures (=60 °C) for individual sonications. Pain was assessed using the visual analog scale (VAS). Results: All patients tolerated the MRgFUS treatment well. No skin toxicity or other complications were observed. The VAS pain rating was significantly reduced for all 6 patients from 8.2 ± 0.8 before treatment to 4.7 ± 3, 2.7 ± 1.5 and 1.8 ± 1.1 at one day, one month and three months respectively. Conclusions: A comprehensive QA program has been developed for the MRgFUS system. Our data suggest that MRgFUS is a safe, effective and noninvasive treatment modality for palliation of bone metastases.

MRgFUS treatment of uterine fibroid in a nulliparous woman with acute retention of urine

Uterine fibroids are the most common tumors of the female reproductive tract. Although most fibroids are asymptomatic, about 25% are associated with symptoms that can have a significant impact on patient's quality of life, including prolonged or excessive menstrual bleeding, pelvic pain or bulkiness, dyspareunia, increased urinary frequency, and infertility. Various treatment options available for symptomatic uterine fibroids include hysterectomy, myomectomy (abdominal or laparoscopic), uterine artery embolization, MR-guided Focused Ultrasound (MRgFUS), and hormonal therapy, which also is sometimes used as adjuvant to other therapies. MRgFUS is a non-invasive treatment approach for symptomatic uterine fibroids. The following case report demonstrates successful treatment of a fibroid that is hyper-intense on T2WIs by MRgFUS with immediate alleviation of pressure symptoms on the urinary bladder.

TH‐C‐204B‐06: MR Guided High‐Intensity Focused Ultrasound for Cancer Therapy: A Feasibility Study Using an Animal Model

Purpose: Ultrasound is a non‐invasive agent that has high precision and deep penetration in tissues enabling increased doses to the tumor while sparing nearby normal tissues. MR guided focused ultrasound (MRgFUS) thermal ablation has been applied for cancer surgery and bone palliation clinically. The aim of this work is to explore the feasibility of MRgFUS for prostate cancer therapy. Method and Materials: An InSightec ExAblate 2000 with a 1.5T GE MR scanner was used in this study. Suitable ultrasound parameters were investigated to perform non‐thermal sonications keeping the temperature below 42°C as measured in real time by MR thermometry. LNCaP cells (106) were injected into the prostate of male mice (n=8). When tumors reached the volume of 49±3mm3 on MRI the tumor‐bearing mice were treated with MRgFUS once a week for two consecutive weeks. Animals were treated with pulsed ultrasound (1MHz; 5W acoustic power; 5Hz frequency; 0.5duty cycle: 0.1sec power on 0.1sec power off) for 60sec in each sonication. A total of 4–6 sonications were used to cover the entire tumor volume. The animals were allowed to survive for 4 weeks after the last treatment. The tumor growth was monitored on MRI and compared with the control group. Results: Significant tumor growth delay was observed in the mice treated with MRgFUS. The mean tumor volume for the MRgFUS treated mice was about 30% smaller than that of the control mice 1 week after the MRgFUS treatment and it was about 50% smaller 4 weeks after the MRgFUS treatment. Conclusions: Our results demonstrated that non‐thermal MRgFUS has a great potential for cancer therapy. Further experiments are needed to derive optimal ultrasound parameters and fractionation schemes to maximize the therapeutic effect. This work is supported by Focused Ultrasound Surgery Foundation DOD PC073127 and Varian Medical Systems. Technical support from InSightec is acknowledged.

SU‐GG‐I‐139: Synergetic Effect of Docetaxel and MR Guided Focused Ultrasound (MRgFUS) for Prostate Cancer

Purpose: Our previous studies showed increased 3H‐docetaxel concentration in prostate tumors in the MRgFUS treated group compared with the control group. The purpose of this study is to determine if MRgFUS increases the efficacy of docetaxel in inhibiting prostate tumor growth. Method and Materials: LNCaP cells (106) were injected into the prostate of male mice. When tumors reached the volume of 47 ± 3 mm3 on MRI, treatment was performed using an InSightec ExAblate 2000 with a 1.5 T GE MR scanner. The animals were randomly divided into 3 groups (n=5/group). For group 1, mice were treated with MRgFUS once a week for two consecutive weeks. Animals were treated with pulsed ultrasound using 1MHz; 5 W acoustic power and the 81 mode setting (5 Hz frequency with 0.1s power on, 01s power off) for 60 seconds for one sonication. Multiple sonications (4–6) were used to cover the whole tumor volume. Immediately after the MRgFUS treatment, docetaxel (10mg/kg) was injected by tail vein. The animal was allowed to survive for 4 weeks after the last treatment. The tumor growth was monitored on MRI. Animals in Group 2 were treated with Docetaxel injection only. Animals in group 3 were used as control. Results: The relative tumor volume in MRgFUS + Docetacel treated group was 0.788 ± 0.07 and 0.75 ±0.11 1 week and 4 weeks after the last MRgFUS treatment, respectively, while for the group received only Docetaxel it was 0.908 ± 0.23 and 1.48 ± 0.54 1 at week and 4 weeks, respectively. Both groups showed smaller tumor volumes compared to the control group. Conclusions: MRgFUS has a potential to increase the efficacy of docetaxel in inhibiting prostate cancer growth. More experiments are under way for optimal ultrasound treatment parameters to improve the synergetic effect.

SU‐FF‐J‐46: Treatment of Bone Metastases Using MR Guided Focused Ultrasound

Purpose: To evaluate the safety and efficacy of MR guided focused ultrasound (MRgFUS) treatment for bone metastases. Method and Materials: A 50‐year‐old patient with painful scapula bone metastases refractory to pain medication was recruited in this study. The treatment was performed under local IRB approval using an MRgFUS system consisting of an Insightec ExAblate 2000 with a GE 1.5T MR scanner. The focal region is approximately 2mm in diameter and 10mm in length. Beside the regular monthly and annual quality assurance (QA) measurements, pre‐treatment machine calibration included the functionality of the treatment software and the mechanical motion control. The focal spot was verified using MR thermometry. The safety system and panic buttons were checked. The patient is positioned on a gel pad on the treatment table in line with the transducer. The gel pad was immersed in degassed water that acts as an interface between the treatment table and the gel pad for acoustic coupling. Caution was taken with all gas bubbles removed between the interfaces. Treatment was performed under conscious sedation. Six sonications were delivered with frequency 1 MHz, acoustic power 32 ±4 W, energy 628±78 J and 20s durations. Phase MR Images were used to monitor the temperature change in real‐time. Based on the treatment feed back, acoustic power was adjusted to reach designed temperatures (⩾60 °C) for individual sonications. Results: The patient tolerated the MRgFUS treatment well. There were no treatment‐related adverse events including skin toxicity. The patient reported rapid pain decrease from 8 out of 10 (0 – 10 scale) pretreatment to 2 within 24 hrs, and has continued to report between 2 – 2.5 up to 2 months following treatment.Conclusions: MRgFUS is a safe, effective and noninvasive treatment modality for bone palliation and pain relief. A comprehensive QA program has been developed for the MRgFUS system.

Initial evaluation of acoustic reflectors for the preservation of sensitive abdominal skin areas during MRgFUS treatment

During MR-guided focused ultrasound (MRgFUS) treatments of uterine fibroids using ExAblate®2000 (InSightec, Haifa, Israel), individual tissue ablations are performed extracorporeally through the patient's abdomen using an annular array FUS transducer embedded within the MR table. Ultrasound intensities in the near field are below therapeutic levels and, under normal conditions, heating of the patient skin is minimal. However, increased absorption of ultrasound energy within sensitive skin areas or areas with differing acoustic properties, such as scars, may lead to skin burns and therefore these areas must be kept outside the near field of the FUS beam. Depending on their location and size the sensitive areas may either obstruct parts of the fibroid from being treated or prevent the entire MRgFUS treatment altogether. The purpose of this work is to evaluate acoustic reflector materials that can be applied to protect skin and the underlying sensitive areas. Reflection coefficients of cork (0.88) and foam (0.91) based materials were evaluated with a hydrophone. An ExAblate 2000 MRgFUS system was used to simulate clinical treatment with discs of reflector materials placed in a near field underneath a gel phantom. MR thermometry was used to monitor temperature elevations as well as the integrity of the focal spot. The phantom measurements showed acoustic shadow zones behind the reflectors with zone depths changing between 7 and 27 mm, for reflector disc diameters increasing from 10 to 30 mm (40 mm diameter discs completely blocked the FUS beam at the depth evaluated). The effects on thermal lesions due to the presence of the reflectors in the FUS beam were found to diminish with decreasing disc diameter and increasing sonication depth. For a 20 mm diameter disc and beyond 50 mm sonication depth, thermal lesions were minimally affected by the presence of the disc. No heating was observed on the skin side of the foam reflectors, as confirmed by measurements performed with adhesive temperature labels. We present these data and discuss possible applications to clinical MRgFUS treatments.

MO-E-AUD C-04: MR Guided Focused Ultrasound (MRgFU) for Treatment of Prostate Cancer: Feasibility Study of Incresing Intratumoral Uptake of Docetaxel in Vivo

Purpose: Docetaxel has been used for the treatment of advanced hormonerefractory prostate cancer and it is also a potent radio‐sensitizer. Our goal is to determine if pulsed MR guided focused ultrasound (MRgFU) will enhance the intratumoral concentration of docetaxel. Method and Materials: This study was performed on an InSightec ExAblate 2000 HIFU system together with a 1.5T GE MR scanner. Human prostate cancer cells LNCaP 105, were grown orthotopically in the prostates of nude mice. A radioactive tritiated Docetaxel ( 3 H ‐ Docetaxel ) was used to determine the uptake enhancement into prostate tumor. Fifteen mice were randomly divided into 3 groups (Group 1, MRgFU + 3 H ‐ Docetaxel ; Group 2, 3 H ‐ Docetaxel only; Group 3, control). The tumors (163 ± 9.0mm3) were treated using pulsed ultrasound with an acoustic power of 4W, pulse width 100msec and 300 pulses in one sonication. The focal peak was set within the target using MR guidance. Eight to ten sonications were used to cover the whole tumor. Immediately after the treatment 3 H ‐ Docetaxe , dissolved in PBS, was given by tail vein injection at doses of 15 mg/kg and a tracer amount of 1.25 uCi/25g. After 0.5 hr, the animals were euthanized and tumors removed. Tumortissues were digested in solubilizing reagent for 2hr at 55°C and decolorized by hydrogen peroxide. The digested samples were added to liquid scintillation cocktail and counted using a liquid scintillator. Results: Our preliminary results showed that the animals tolerated well the MRgFU treatment. The average of radioactive cpm counts in the MRgFU treated group is 2 folds more than that without the HIFU treatment. The variation is large between individual animals and further experiments are being conducted to reduce the experimental uncertainty. Conclusion: MRgFU may have a great potential as a safe, noninvasive treatment modality for the enhancement of docetaxel for prostate cancer therapy.