MR-Guided Focused Ultrasound Thalamotomy in the Setting of Aneurysm Clip.

We report on a 75-year-old woman with a history of right MCA aneurysm clipping and medically refractive right-hand tremor. We successfully performed focused ultrasound thalamotomy of the left ventral intermediate nucleus under MR imaging-guidance at 3T. A thorough pretreatment evaluation of MR thermometry was critical to ensure that adequate precision could be achieved at the intended target. The tremor showed a 75% decrease at 24 hours postprocedure and a 50% decrease at a 3-month follow-up. There were no immediate adverse events.

Non-invasive central nervous system assessment of a porcine model of neuropathic pain demonstrates increased latency of somatosensory-evoked potentials.

BACKGROUND: The study of chronic pain and its treatments requires a robust animal model with objective and quantifiable metrics. Porcine neuropathic pain models have been assessed with peripheral pain recordings and behavioral responses, but thus far central nervous system electrophysiology has not been investigated. This work aimed to record non-invasive, somatosensory-evoked potentials (SEPs) via electroencephalography in order to quantitatively assess chronic neuropathic pain induced in a porcine model. NEW METHOD: Peripheral neuritis trauma (PNT) was induced unilaterally in the common peroneal nerve of domestic farm pigs, with the contralateral leg serving as the control for each animal. SEPs were generated by stimulation of the peripheral nerves distal to the PNT and were recorded non-invasively using transcranial electroencephalography (EEG). The P30 wave of the SEP was analyzed for latency changes. RESULTS: P30 SEPs were successfully recorded with non-invasive EEG. PNT resulted in significantly longer P30 SEP latencies (p < 0.01 [n = 8]) with a median latency increase of 14.3 [IQR 5.0 - 17.5] ms. Histological results confirmed perineural inflammatory response and nerve damage around the PNT nerves. COMPARISON WITH EXISTING METHOD(S): Control P30 SEPs were similar in latency and amplitude to those previously recorded invasively in healthy pigs. Non-invasive recordings have numerous advantages over invasive measures. CONCLUSIONS: P30 SEP latency can serve as a quantifiable neurological measure that reflects central nervous system processing in a porcine model of chronic pain. Advancing the development of a porcine chronic pain model will facilitate the translation of experimental therapies into human clinical trials.

Influence of cerebrospinal fluid on power absorption during transcranial magnetic resonance-guided focused ultrasound treatment.

BACKGROUND: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy. PURPOSE: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments. METHODS: Simulations were conducted with imaging data from 20 patients previously treated with focused ultrasound for disabling tremor. The Hybrid Angular Spectrum (HAS) method was used to test the effect of including cerebral spinal fluid (CSF) and brain anatomy in determining the element phases used for aberration correction and beam focusing. Computer tomography (CT) and magnetic resonance imaging (MRI) images from patient treatments were used to construct a segmented model of each patient's head. The segmented model for treatment simulation consisted of water, skin, fat, brain, CSF, diploë, and cortical bone. Transducer element phases used for treatment simulation were determined using time reversal from the desired focus, generating a set of phases assuming a homogeneous brain in the intracranial volume, and a second set of phases assigning CSF acoustic properties to regions of CSF. In addition, for three patients, the relative effect of separately including CSF speed of sound values compared to CSF attenuation values was found. RESULTS: We found that including CSF acoustic properties (speed of sound and attenuation) during phase planning compared to phase correction without considering CSF increased the absorbed ultrasound power density ratios at the focus over a range of 1.06 to 1.29 (mean of 17% ± 6%) for 20 patients. Separately considering the CSF speed of sound and CSF attenuation showed that the increase was due almost entirely to including the CSF speed of sound; considering only the CSF attenuation had a negligible effect. CONCLUSIONS: Based on HAS simulations, treatment planning phase determination using morphologically realistic CSF and brain anatomy yielded an increase of up to 29% in the ultrasound focal absorbed power density. Future work will be required to validate the CSF simulations.

The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods.

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Feasibility of non-invasive recording of somatosensory evoked potential in pigs.

BACKGROUND: Non-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality. RESULTS: Pigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21-47] mcg/kg of dexmedetomidine, 0.3 [0.2-0.3] mg/kg of midazolam, and 0.3 [0.3-0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11-12]; median score at 30 min: 11.5 [10.5-12]). Heart rate (median [range]) (55 [49-71] beats per minute), respiratory rate (24 [21-30] breaths per minute), and hemoglobin oxygen saturation (99 [98-100]%) and body temperature (37.7 [37.4-37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents. CONCLUSIONS: In this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.

Anatomic thermochromic tissue-mimicking phantom of the lumbar spine for pre-clinical evaluation of MR-guided focused ultrasound (MRgFUS) ablation of the facet joint.

OBJECTIVE: To develop a thermochromic tissue-mimicking phantom (TTMP) with an embedded 3D-printed bone mimic of the lumbar spine to evaluate MRgFUS ablation of the facet joint and medial branch nerve. MATERIALS AND METHODS: Multiple 3D-printed materials were selected and characterized by measurements of speed of sound and linear acoustic attenuation coefficient using a through-transmission technique. A 3D model of the lumbar spine was segmented from a de-identified CT scan, and 3D printed. The 3D-printed spine was embedded within a TTMP with thermochromic ink color change setpoint at 60 °C. Multiple high energy sonications were targeted to the facet joints and medial branch nerve anatomical location using an ExAblate MRgFUS system connected to a 3T MR scanner. The phantom was dissected to assess sonication targets and the surrounding structures for color change as compared to the expected region of ablation on MR-thermometry. RESULTS: The measured sound attenuation coefficient and speed of sound of gypsum was 240 Np/m-MHz and 2471 m/s, which is the closest to published values for cortical bone. Following sonication, dissection of the TTMP revealed good concordance between the regions of color change within the phantom and expected areas of ablation on MR-thermometry. No heat deposition was observed in critical areas, including the spinal canal and nerve roots from either color change or MRI. CONCLUSION: Ablated regions in the TTMP correlated well with expected ablations based on MR-thermometry. These findings demonstrate the utility of an anatomic spine phantom in evaluating MRgFUS sonication for facet joint and medial branch nerve ablations.

T2 mapping as a predictor of nonperfused volume in MRgFUS treatment of desmoid tumors.

Objective: The objective of this study was to develop an alternative method of non-contrast monitoring of tissue ablation during focused ultrasound treatment. Desmoid tumors are benign but locally aggressive soft tissue tumors that arise from fibroblast cells. Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as an alternative to conventional therapies, showing promising results in reduction of tumor volume without significant side effects. The gold-standard assessment of the reduction of viable tumor volume post-treatment is non-perfused volume (NPV) and evaluation of NPV is typically performed with post-treatment gadolinium enhanced MR imaging. However, as gadolinium cannot be repeatedly administered during treatments, there is a need for alternative non-contrast monitoring of the tissue to prevent over and under treatment. Methods: Double-echo and multi-echo images were acquired before, during and after the MRgFUS treatment. T2 maps were generated with an exponential fit and T2 maps were compared to post-treatment post-contrast images.Results: In all five MRgFUS treatment sessions, T2 mapping showed excellent qualitative agreement with the post-contrast NPV.Conclusions: T2 mapping may be used to visualize the extent of ablation with focused ultrasound and can be used as a predictor of NPV prior to the administration of contrast during the post-treatment assessment.

The impact of technical parameters on ablation volume during MR-guided focused ultrasound of desmoid tumors.

PURPOSE: Desmoid tumors are benign, locally aggressive soft tissue tumors derived from fibroblasts. Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective treatment for desmoid tumors. The purpose of this study was to retrospectively review the MRgFUS treatments of desmoid tumors at our institution to determine which technical treatment parameters contributed most significantly to the accumulation of thermal dose. MATERIALS AND METHODS: The study protocol was approved by the local IRB. We retrospectively reviewed data from MRgFUS treatments performed in histologically-confirmed desmoid tumors, over a period of 18 months. Sonication parameter means were compared with ANOVA. Mixed effects and linear regression models were used to evaluate the relative contribution of different parameters to thermal dose volume. RESULTS: Nine-hundred thirty-six sonications were reviewed in 13 treatments. Accumulated dose per sonication was greatest for elongated sonications (0.96 cc ± 0.90) compared to short (0.88 ± 0.93 cc) and nominal (0.55 ± 0.70 cc) sonications, p < .001. 65.2% of short sonications resulted in high percentage ablations, compared to 46.0% of nominal and 35.1% of elongated sonications. Standardized beta coefficients (anticipated increased volume in cc per unit) for power, duration, energy and average temperature were 0.006, 0.057, 0.00035 and 0.03, p < .001. Regarding dose efficacy, dose area contributed the greatest to this variability - 50.7% (45.5-54.8%), followed by distance - 16.6% (12.9-20.0%). CONCLUSIONS: A variety of sonication parameters significantly contributed to thermal ablation volume following MRgFUS of desmoid tumors, in reproducible patterns. This work can serve as the basis for future models working toward improved planning for MRgFUS treatments.

MR thermometry-guided ultrasound hyperthermia of user-defined regions using the ExAblate prostate ablation array.

BACKGROUND: Hyperthermia therapy (HT) has shown to be an effective adjuvant to radiation, chemotherapy, and immunotherapy. In order to be safe and effective, delivery of HT requires maintenance of target tissue temperature within a narrow range (40-44 °C) for 30-60 min, which necessitates conformal heat delivery and accurate temperature monitoring. The goal of this project was to develop an MR thermometry-guided hyperthermia delivery platform based upon the ExAblate prostate array that would achieve uniform stable heating over large volumes within the prostate, while allowing the user to precisely control the power deposition patterns and shape of the region of treatment (ROT). METHODS: The HT platform incorporates an accelerated multi-slice real time MR thermometry pulse sequence and reconstruction pipeline. Temperature uniformity over a large contiguous area was achieved by multi-point temperature sampling with multi-focal feedback power control. The hyperthermia delivery system was based on an InSightec ExAblate 2100 prostate focused ultrasound ablation system, and HeartVista's RTHawk real-time MRI system integrated with a 3 T MRI scanner. The integrated system was evaluated in experiments with a tissue-mimicking phantom for prolonged exposures with a target temperature increase of 7 °C from baseline. RESULTS: Five various shapes of the region of treatment, defined on a 5 × 5 grid (35 × 35 mm, 11-25 focal spots per shape), were implemented to evaluate the performance of the system. MR temperature images, acquired after steady state was reached, showed different patterns of heating that closely matched the prescribed regions. Temperature uncertainty of the thermometry acquisition was 0.5 °C. The time to reach the target temperature (2:58-7:44 min) depended on the chosen ROT shape and on the distance from transducer to focal plane. Pre-cooling with circulating water helped to reduce near-field heating. CONCLUSIONS: We have implemented a real-time MR thermometry-guided system for hyperthermia delivery within user-defined regions with the ExAblate prostate array and evaluated it in phantom experiments for different shapes and focal depths. Our results demonstrate the feasibility of using a commercially available endorectal FUS transducer to perform spatially-conformal hyperthermia therapy and could lead to a new set of exciting applications for these devices.

Thermal diffusivity and perfusion constants from in vivo MR-guided focussed ultrasound treatments: a feasibility study.

PURPOSE: This study investigates the feasibility of non-invasively determining thermal diffusivity (α) and the Pennes perfusion parameter (w) from pre-clinical and clinical magnetic resonance-guided focussed ultrasound (MRgFUS) temperature data. MATERIALS AND METHODS: Pre-clinical MRgFUS experiments were performed in rabbit muscle (N = 3, 28 sonications) using three-dimensional MR thermometry. Eight sonications were made in a clinical QA phantom with two-dimensional thermometry. Retrospective property determination was performed on clinical uterine fibroid (N = 8, 9 sonications) and desmoid tumour (N = 4, 7 sonications) data. The property determination method fits an analytical solution to MRgFUS temperatures in the coronal MR plane, including all temperatures acquired during heating and one cooling image. When possible, additional cooling data were acquired for property determination. RESULTS: Rabbit α and w from Heating Data (α = 0.164 mm2s-1, w = 7.9 kg m-3 s-1) and Heating and Cooling Data (α = 0.146 mm2s-1, w = 3.3 kg m-3 s-1) were within the range of gold-standard invasive measurements, with >50% reduction in variability by including cooling data. QA phantom property determination with cooling data yielded properties within 3% of expected values (α = 0.144 mm2s-1, w = 0.0 kg m-3 s-1), a difference that was not statistically significant (p = 0.053). Uterine fibroid (Heating Data: α = 0.212 mm2s-1, w = 11.0 kg m-3 s-1) and desmoid tumour (Heating & Cooling Data: α = 0.245 mm2s-1, w = 4.7 kg m-3 s-1) properties are feasible but lack independent verification. CONCLUSIONS: Thermal diffusivity and the Pennes perfusion parameter can be obtained from in vivo data and with clinical MRgFUS protocols. Property values are consistently improved by including cooling data. The utility of this property determination method will increase as clinical protocols implement improved temperature imaging.

Effect of Sonication Duration and Power on Ablation Depth During MR-Guided Focused Ultrasound of Bone.

PURPOSE: To evaluate the effect of differences in sonication duration and power on the size of postcontrast ablation zone following magnetic resonance-guided focused ultrasound (MRgFUS) of bone in a swine femoral bone model. MATERIALS AND METHODS: Experimental procedures received approval from the Institutional Committee on Animal Research. MRgFUS was used to create two thermal lesions in the left femur of six pigs. Each target was subjected to six sonications. 400J of energy was used for each sonication. However, the distal target received the standard sonication duration of 20 seconds (20W), while the proximal target received a longer sonication duration of 40 seconds (10W). MRgFUS lesions were imaged with fat-saturated spoiled gradient echo sequence at 3.0T MRI 10 minutes following the administration of contrast. Maximum three-plane dimensions of the hypoenhanced ablation area were measured. RESULTS: Postcontrast MR images demonstrated ovoid regions of hypoenhancement at each target. The average depth of ablation was significantly greater for the shorter high-power sonications (7.3 mm), compared to the longer lower-power sonications (4.5 mm), P = 0.026. The craniocaudal dimension was also greater for the shorter ablations 26.7 mm compared to the longer sonications 21.0 mm, P = 0.006. CONCLUSION: Contrary to anecdotal clinical experience, this preclinical model suggests that during MRgFUS of bone, standard duration, higher-power sonications resulted in deeper ablation volumes compared to long duration, lower-power sonications. These results suggest that to achieve deeper ablations, if longer sonications are used, then the power should be relatively maintained, for a net energy increase. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1418-1422.

MRgFUS for desmoid tumors within the thigh: early clinical experiences.

BACKGROUND: Desmoid tumors are benign but locally aggressive non-malignant tumors derived from fibroblasts. Surgery, chemotherapy, and radiation therapy have been the mainstay of treatment, but recurrence is common and side effects can result in significant morbidity. In this case series, we highlight our experiences performing treatments in the thigh, including strategies for optimizing ablation size and safety. CASE PRESENTATION: Since December 2014, 14 magnetic resonance-guided focused ultrasound (MRgFUS) treatments for desmoid tumors were performed at our institution in seven patients. Nine of these treatments were completed in three patients with large tumors within the posterior thigh. The first was a 7-year-old boy who had previously been treated with surgical resection, intra-operative radiation, along with courses of vinblastine/methotrexate and sorafenib. Pretreatment tumor volume was 770 cm3 with 75% non-enhancing volume following the initial treatment. The first treatment was complicated by a third-degree far-field skin burn. Enhanced safety measures were developed to protect the far-field skin. The patient had four subsequent treatments over 14 months, without complication, with non-perfused volume of 85% on current imaging. The second patient was a 21-year-old woman who had previously taken sulindac and celecoxib but had no other therapy. Pretreatment tumor volume was 740 cm3. The lateral decubitus position was used to minimize the amount of energy through the sciatic nerve. The first treatment resulted in a relatively low non-perfused volume of 30%. A follow-up treatment resulted in 75-80% ablation of the target. The third patient was a 14-year-old girl with no prior treatment. Pretreatment tumor volume was approximately 440 cm3. The sciatic nerve was encased by the anteromedial portion of the mass. A lateral decubitus position and enhanced safety measures were again used. The first treatment resulted in a relatively low non-perfused volume of 30%, likely related to low energies. The second treatment resulted in 70-80% ablation. CONCLUSIONS: MRgFUS is an effective treatment for desmoid tumors of the thigh with a favorable side effect profile, allowing for repeated treatments if necessary. Ablation size and safety can be improved with far-field coupling devices, careful patient positioning, and optimized sonication planning.

T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound.

BACKGROUND: Current clinical protocols for MR-guided focused ultrasound (MRgFUS) treatment of osseous lesions, including painful bone metastases and osteoid osteomas, rely on measurement of the temperature change in adjacent muscle to estimate the temperature of the bone. The goal of this study was to determine if T2-based thermometry could be used to monitor the temperature change in bone marrow during focused ultrasound ablation of bone lesions. METHODS: We investigated the dependence of T2 on temperature in ex vivo bovine yellow bone marrow at 3T and studied the influence of acquisition parameters on the T2 measurements. We examined if T2 changes in red bone marrow caused by the ablation of ex vivo trabecular bone were reversible and measured the patterns of heating and tissue damage. The technique was validated during the ablation of intact ex vivo bone samples and an in vivo animal model. RESULTS: Results of the calibration experiment showed a linear relationship (7 ms/°C) between T2 change and temperature and could be used to quantify the temperature during heating of up to 60 °C. During trabecular bone ablation, we observed a linear relationship (5.7 ms per °C) between T2 and temperature during the heating stage of the experiment. After cool down, there was residual T2 elevation (~35 ms) in the ablated area suggesting irreversible tissue changes. In ex vivo and in vivo cortical bone ablation experiments, we observed an increase in T2 values in the marrow adjacent to the intersection of the cortical bone and the beam path. The in vivo experiment showed excellent correspondence between the area of T2 elevation in marrow during the ablation and the resulting non-enhancing area in the post-contrast images. CONCLUSIONS: In this study, we have demonstrated that T2-based thermometry can be used in vivo to measure the heating in the marrow during bone ablation. The ability to monitor the temperature within the bone marrow allowed more complete visualization of the heat distribution into the bone, which is important for local lesion control.

Evaluation of MRI protocols for the assessment of lumbar facet joints after MR-guided focused ultrasound treatment.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) might be a very safe and effective minimally invasive technique to treat facet joint pain caused by arthritis and other degenerative changes. However, there are still safety concerns for this treatment and challenges regarding MR imaging and temperature mapping due to susceptibility effects between the bone and soft tissue near the joint, which has resulted in poor MR image quality. The goal of this research was to evaluate multiple magnetic resonance imaging (MRI) pulse sequences for characterizing ablated lumbar facet joint lesions created by high-intensity focused ultrasound (FUS) and compare the findings to histological tissue assessment. In particular, we investigated the use of T2-weighted MRI to assess treatment effects without contrast administration. METHODS: An IACUC approved study (n = 6 pigs) was performed using a 3T widebore MRI system equipped with an MRgFUS system. Facet joints of the lumbar vertebra were ablated using 1-MHz frequency and multiple sonication energies (300-800 J). In addition to T2-weighted MRI for treatment planning, T1-, T2-, and T2*-weighted and perfusion MRI sequences were applied. Signal intensity ratios of the lesions were determined. Histopathology was used to characterize cellular changes. RESULTS: Ablation of the facet joint, using MRgFUS, was successful in all animals. T2-weighted images showed high signal intensity in the edematous facet joint and adjacent muscle, while delayed contrast-enhanced T1-weighted images showed an enhanced ring surrounding the target volume. T2*-weighted GRE images revealed inconsistent lesion visualization. Histopathology confirmed the presence of cellular coagulation (shrinkage), extracellular expansion (edema), and hemorrhage in the bone marrow. CONCLUSIONS: MRgFUS provided sufficient precision and image quality for visualization and characterization of ablated facet joints directly after ablation. MRI may help in monitoring the efficacy of FUS ablation without contrast after treating patients with back pain.

PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids.

OBJECTIVE: To evaluate the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids (MRgFUS) and obtain estimates of safety and efficacy. DESIGN: Pilot, randomized, placebo-controlled trial. SETTING: University medical center. PATIENT(S): Premenopausal women with symptomatic uterine fibroids. INTERVENTION(S): Participants randomized in a 2:1 ratio to receive MRgFUS or placebo procedure. PRIMARY OUTCOME: change in fibroid symptoms from baseline to 4 and 12 weeks after treatment assessed by the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL); secondary outcome: incidence of surgery or procedures for recurrent symptoms at 12 and 24 months. RESULT(S): Twenty women with a mean age of 44 years (±standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and 7 to placebo. Four weeks after treatment, all participants reported improvement in the UFS-QOL: a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks. Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure. CONCLUSION(S): Women with fibroids were willing to enroll in a randomized, placebo-controlled trial of MRgFUS. A placebo effect may explain some of the improvement in fibroid-related symptoms observed in the first 12 weeks after MRgFUS. CLINICAL TRIAL REGISTRATION NUMBER: NCT01377519.

T2-based temperature monitoring in abdominal fat during MR-guided focused ultrasound treatment of patients with uterine fibroids.

BACKGROUND: Near-field heating is a potential problem in focused ultrasound treatments, as it can result in thermal injury to skin, subcutaneous fat, and other tissues. Our goals were to determine if T2-based temperature mapping could be used reliably to measure near-field heating in adipose tissue and whether it is practical to perform such mapping during focused ultrasound treatments. METHODS: We investigated the dependence of T2 on temperature in ex vivo adipose tissue at 3T using a double-echo fast spin echo (FSE) sequence. We implemented and evaluated the T2-based temperature mapping technique in the adipose tissue of two healthy volunteers. Finally, we applied the technique during magnetic resonance-guided focused ultrasound (MRgFUS) treatments to measure near-field heating in eight patients with uterine fibroids. RESULTS: Calibration experiments in porcine adipose tissue determined a temperature coefficient of 6.16 ms/°C during heating and 5.37 ms/°C during cooling. The volunteer experiments demonstrated a strong correlation between the skin temperature and T2-based temperature measurements in the fat layer. During the treatments of patients with uterine fibroids, we observed a measurable change in the T2 of fat tissue within the path of the ultrasound beam and a temperature increase of up to 15 °C with sustained heating of more than 10 °C. CONCLUSIONS: Our results demonstrate the feasibility and importance of monitoring near-field heating in fatty tissues. The implementation of near-field monitoring between sonications can shorten treatments by reducing the cooling time. It can help improve safety by avoiding excessive heating in the near field.

Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI.

PURPOSE: To demonstrate the feasibility of using ultrashort echo-time MRI to quantify T1 changes in cortical bone due to heating. METHODS: Variable flip-angle T1 mapping combined with 3D ultrashort echo-time imaging was used to measure T1 in cortical bone. A calibration experiment was performed to detect T1 changes with temperature in ex vivo cortical bone samples from a bovine femur. Ultrasound heating experiments were performed using an interstitial applicator in ex vivo bovine femur specimens, and heat-induced T1 changes were quantified. RESULTS: The calibration experiment demonstrated that T1 increases with temperature in cortical bone. We observed a linear relationship between temperature and T1 with a linear coefficient between 0.67 and 0.84 ms/°C over a range of 25-70°C. The ultrasound heating experiments showed increased T1 changes in the heated regions, and the relationship between the temperature changes and T1 changes was similar to that of the calibration. CONCLUSION: We demonstrated a temperature dependence of T1 in ex vivo cortical bone using a variable flip-angle ultrashort echo-time T1 mapping method.

International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions.

Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

Bone remodeling after MR imaging-guided high-intensity focused ultrasound ablation: evaluation with MR imaging, CT, Na(18)F-PET, and histopathologic examination in a swine model.

PURPOSE: To serially monitor bone remodeling in the swine femur after magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) ablation with MR imaging, computed tomography (CT), sodium fluorine 18 (Na(18)F)-positron emission tomography (PET), and histopathologic examination, as a function of sonication energy. MATERIALS AND METHODS: Experimental procedures received approval from the local institutional animal care and use committee. MR imaging-guided HIFU was used to create distal and proximal ablations in the right femurs of eight pigs. The energy used at the distal target was higher (mean, 419 J; range, 390-440 J) than that used at the proximal target (mean, 324 J; range, 300-360 J). Imaging was performed before and after ablation with 3.0-T MR imaging and 64-section CT. Animals were reevaluated at 3 and 6 weeks with MR imaging (n = 8), CT (n = 8), Na(18)F-PET (n = 4), and histopathologic examination (n = 4). Three-dimensional ablation lengths were measured on contrast material-enhanced MR images, and bone remodeling in the cortex was measured on CT images. RESULTS: Ablation sizes at MR imaging 3 and 6 weeks after MR imaging-guided HIFU ablation were similar between proximal (low-energy) and distal (high-energy) lesions (average, 8.7 × 21.9 × 16.4 mm). However, distal ablation lesions (n = 8) demonstrated evidence of subperiosteal new bone formation at CT, with a subtle focus of new ossification at 3 weeks and a larger focus of ossification at 6 weeks. New bone formation was associated with increased uptake at Na(18)F-PET in three of four animals; this was confirmed at histopathologic examination in four of four animals. CONCLUSION: MR imaging-guided HIFU ablation of bone may result in progressive remodeling, with both subcortical necrosis and subperiosteal new bone formation. This may be related to the use of high energies. MR imaging, CT, and PET are suitable noninvasive techniques to monitor bone remodeling after MR imaging-guided HIFU ablation.

MRI-guided high-intensity focused ultrasound ablation of bone: evaluation of acute findings with MR and CT imaging in a swine model.

PURPOSE: To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and computed tomography (CT) imaging following MR-guided high-intensity focused ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and energy. MATERIALS AND METHODS: Experimental procedures received approval from the local Institutional Animal Care and Use Committee. MRgHIFU was used to create distal and proximal ablations in the right femur of eight pigs. Each target was dosed with four or six sonications within similar volumes. The energy dosed to the distal target was higher (419 ± 19 J) than the proximal target (324 ± 17 J). The targeted femur and contralateral control were imaged before and after ablation using MR at 3T. Qualitative changes in signal on T1-weighted, T2-weighted, and T1-weighted postcontrast images were assessed. Ablation dimensions were calculated from postcontrast MRI. The 64-slice CT images were also obtained before and after ablation and qualitative changes were assessed. RESULTS: MRgHIFU bone ablation size measured on average 8.5 × 21.1 × 16.2 mm (transverse × craniocaudal × anteroposterior). Interestingly, within similar prescribed volumes, increasing the number of sonications from 4 to 6 increased the depth of the intramedullary hypoenhanced zone from 2.9 mm to 6.5 mm (P < 0.001). There was no difference in the appearance of low versus high energy ablations. CT imaging did not show structural abnormalities. CONCLUSION: The number of MRgHIFU focal sonications can be used to increase the depth of treatment within the targeted bone. Unlike CT, T2-weighted and contrast-enhanced MR demonstrated the hyperacute structural changes in the femur and surrounding soft tissue.