Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve.

INTRODUCTION: Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH). MATERIAL AND METHODS: Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24-48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied. RESULTS: The median AMH level before the HIFU treatment was 1.20 (range: 0.1-7.75 ug/L) and after the treatment 1.23 (range: 0.1-8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment. CONCLUSIONS: MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels.

Histological findings in resected leiomyomas following MR-HIFU treatment, single-institution data from seven patients with unfavorable focal therapy.

PURPOSE: Magnetic resonance - high-intensity focused ultrasound (MR-HIFU) is a noninvasive treatment option for symptomatic uterine leiomyomas. Currently, pretreatment MRI is used to assess tissue characteristics and predict the most likely therapeutic response for individual patients. However, these predictions still entail significant uncertainties. The impact of tissue properties on therapeutic outcomes remains poorly understood and detailed knowledge of the histological effects of ultrasound ablation is lacking. Investigating these aspects could aid in optimizing patient selection, enhancing treatment effects and improving treatment outcomes. METHODS AND MATERIALS: We present seven patients who underwent MR-HIFU treatment for leiomyoma followed by second-line surgical treatment. Tissue samples obtained during the surgery were stained with hematoxylin and eosin, Masson's trichrome and Herovici to evaluate general morphology, fibrosis and collagen deposition of leiomyomas. Immunohistochemical CD31, Ki-67 and MMP-2 stainings were performed to study vascularization, proliferation and matrix metalloproteinase-2 protein expression in leiomyomas, respectively. RESULTS: The clinical characteristics and radiological findings of the leiomyomas prior to treatment as well as qualitative histological findings after the treatment are presented and discussed in the context of current literature. A tentative model for volume reduction is presented. CONCLUSION: These findings provide insights into potential factors contributing to suboptimal therapeutic outcomes and the variability in histological changes following treatment.

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives.

OBJECTIVES: The aim of this review was to analyze and summarize the most common adverse events (AEs) and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids (UFs) and to establish the risk factors of their occurrence. METHODS: We searched for original research studies evaluating MRgFUS therapy in UFs with outcomes containing AEs and/or complications in different databases (PubMed/MEDLINE, SCOPUS, COCHRANE) until March 2022. Reviews, editorials, opinions or letters, case studies, conference papers and abstracts were excluded from the analysis. The systematic literature search identified 446 articles, 43 of which were analyzed. RESULTS: According to available evidence, the overall incidence of serious complications in MRgFUS therapy is relatively low. No AEs/complications were reported in 11 out of 43 analyzed studies. The mean occurrence of all AEs in the analyzed material was 24.67%. The most commonly described AEs included pain, skin burns, urinary tract infections and sciatic neuropraxia. Major AEs, such as skin ulcerations or deep vein thrombosis, occurred in 0.41% of cases in the analyzed material. CONCLUSION: MRgFUS seems to be safe in UF therapy. The occurrence of AEs, especially major ones, is relatively low in comparison with other methods. The new devices and more experience of their users seem to reduce AE rate. The lack of unification in AE reporting and missing data are the main issues in this area. More prospective, randomized studies with unified reporting and long follow-up are needed to determine the safety in a long-term perspective.

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery.

BACKGROUND: Trans-cranial MR guided focused ultrasound (tcMRgFUS) ablation targets are <5mm from critical neurological structures, creating a need for improved MR imaging and thermometry. The purpose of this study was to evaluate the performance of a dual-channel radiofrequency receive-only head coil designed specifically for integrated use in tcMRgFUS. METHODS: Imaging used a 3 T MRI and the ExAblate Neuro System (INSIGHTEC Inc., Israel). Sensitivity maps determined receive-only coil uniformity. The head coil was compared to the volume body coil at the level of the thalamus using 1) T2-weighted imaging and 2) multi-echo MR thermometry of volunteers in the transducer helmet. Thermal sonications (40 W, 24s) were acquired in a heating phantom. Thermal maps in were constructed to evaluate temperature uncertainty, focal heating, and temperature evolution. RESULTS: The normalized signal intensity showed up to a 35% variation. On T2wFSE images the SNR with the head coil is improved by 4x in the axial plane, and 3x in sagittal and coronal planes. The head coil provided better visualization of the thalamus and globus pallidus (axial), and of the anterior/posterior commissure, and brain stem/cerebellum (sagittal) compared to the body coil. MR thermometry showed a 4x gain in SNR in the thalamus. Thermometry showed a preserved focal spot with 20 °C temperature rise. The average temperature uncertainty (mean ± std) was reduced from σ T = 0.96 °C ± 0.55 °C for the body coil to σ T = 0.41 °C ± 0.24 °C for the head coil. CONCLUSIONS: Greater SNR from the dual-channel head coil provides access to better treatment day visualization for treatment planning and higher precision intra-operative thermometry.

Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation.

INTRODUCTION: Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique. MATERIALS AND METHODS: 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401. RESULTS: Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin (p ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups (p = 0.04). CONCLUSION: Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.

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

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

Feasibility of targeting canine soft tissue sarcoma with MR-guided high-intensity focused ultrasound.

PURPOSE: Magnetic resonance imaging-guided high-intensity-focused ultrasound (MR-HIFU) is a non-invasive treatment modality that precisely focuses ultrasound energy within a tumour and can be customised to result in a wide range of local bioeffects. The purpose of this study was to determine the feasibility of using MR-HIFU to treat soft tissue sarcoma (STS) in dogs. MATERIALS AND METHODS: Medical records of dogs admitted to the Virginia-Maryland College of Veterinary Medicine from 1 January 2012 to 31 December 2016 were searched for a diagnosis of sarcoma with available cross-sectional imaging of the tumour (MRI or CT). Fifty-three (53) dogs were eligible for inclusion. Tumor tissue (in bone as well as in soft tissue) was considered targetable unless: (1) the ultrasound path was completely obstructed by bone or gas and (2) the MR-HIFU target was within the spinal cord or less than 1 cm from the margin of the spinal cord. Tumors were categorised as <50% targetable, ≥50% targetable or non-targetable. RESULTS: Eighty-one percent of STS (81.1%, 43/53) were targetable. The head/spine tumour sites had the highest proportion of non-targetable tumours (36%, 9/25). The majority of truncal and axillary tumours were ≥50% targetable (88.9%, 16/18) ,and all extremity tumours were considered ≥50% targetable (100%, 5/5). CONCLUSIONS: The majority of STS were targetable. This is the first study to evaluate MR-HIFU targetability of canine STS. HIFU has potential as a therapeutic modality for treating STS in dogs, and this veterinary application is a possible model for treatment of naturally occurring STS in humans.

Mid-term results of MR-guided high-intensity focused ultrasound treatment for relapsing superficial desmoids.

PURPOSE: Desmoids are locally infiltrative, nonmalignant soft tissue tumors. Surgery, radiation therapy, and chemotherapy have been the mainstay of treatment, but relapse is common and side effects can result in significant morbidity. MR-HIFU is increasingly recognized as an alternative treatment modality. We assessed the success rate of MR-HIFU for the treatment of extra-abdominal desmoids at our institute. MATERIALS AND METHODS: Five patients with relapsing desmoid tumors (three males, two females; age range 40-79 years) were treated using the Sonalleve system in an outpatient setting without general anesthesia. Changes in total tumor volumes were measured with a tumor tracking software. Adverse events were documented. RESULTS: MR-HIFU was successful in all patients without severe side effects. Follow up ranged from 13 to 60 months. Three patients required more than one treatment session. In 3 patients with small lesions (mean = 9.7 mL), complete ablation was achieved with no evidence of viable tumor on follow up MRI at an average of 35.7 months, while in two patients with larger lesions (mean = 46 mL) the targeted tumor volumes decreased by 73% at 14 months. Skin injuries comprised first- and second-degree burns and were observed with short distance to skin (mean = 0.9 cm) and proximity to bone (i.e. ribs). Skin burns healed within weeks with topical treatment. CONCLUSION: MR-HIFU shows good mid-term result for extra-abdominal desmoids with complete response for small lesions and stabilization of larger lesions. MR-HIFU for desmoids can be performed under regional anesthesia/sedation as outpatients.

Breath-hold MR-HIFU hyperthermia: phantom and in vivo feasibility.

Background: The use of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) to deliver mild hyperthermia requires stable temperature mapping for long durations. This study evaluates the effects of respiratory motion on MR thermometry precision in pediatric subjects and determines the in vivo feasibility of circumventing breathing-related motion artifacts by delivering MR thermometry-controlled HIFU mild hyperthermia during repeated forced breath holds.Materials and methods: Clinical and preclinical studies were conducted. Clinical studies were conducted without breath-holds. In phantoms, breathing motion was simulated by moving an aluminum block towards the phantom along a sinusoidal trajectory using an MR-compatible motion platform. In vivo experiments were performed in ventilated pigs. MR thermometry accuracy and stability were evaluated.Results: Clinical data confirmed acceptable MR thermometry accuracy (0.12-0.44 °C) in extremity tumors, but not in the tumors in the chest/spine and pelvis. In phantom studies, MR thermometry accuracy and stability improved to 0.37 ± 0.08 and 0.55 ± 0.18 °C during simulated breath-holds. In vivo MR thermometry accuracy and stability in porcine back muscle improved to 0.64 ± 0.22 and 0.71 ± 0.25 °C during breath-holds. MR-HIFU hyperthermia delivered during intermittent forced breath holds over 10 min duration heated an 18-mm diameter target region above 41 °C for 10.0 ± 1.0 min, without significant overheating. For a 10-min mild hyperthermia treatment, an optimal treatment effect (TIR > 9 min) could be achieved when combining 36-60 s periods of forced apnea with 60-155.5 s free-breathing.Conclusion: MR-HIFU delivery during forced breath holds enables stable control of mild hyperthermia in targets adjacent to moving anatomical structures.

The effect of high-intensity focused ultrasound guided by magnetic resonance therapy on obstetrical outcomes in patients with uterine fibroids - experiences from the main Polish center and a review of current data.

Introduction: Uterine fibroids (UFs) are benign tumors of female genital tract. Clinically symptomatic UFs may be a cause of serious health problems for many women worldwide. The optimal choice of a treatment method should fit a patient's specific life situation or expectancies (especially fertility) as much as possible. In line with the general current trend in medicine and surgery, great importance is attached to the development of minimally invasive radiological procedures e.g., magnetic resonance guided focused ultrasound (MRgFUS). Materials and methods: Single-center retrospective cohort study conducted at the Department of Obstetrics and Gynecology of Pro-Familia Hospital in Rzeszów, Poland. The study group consisted of 276 patients suffering from UFs and treated with MR-HIFU over the period from April 2015 to May 2018. Results: In our group 20 out of 276 patients conceived after the MR-HIFU therapy (7.25%). A general improvement and alleviation of symptoms of the disease after MRgFUS/MR-HIFU procedure were observed in 80% (n = 16) of study participants that conceived. 15% (n = 3) did not report any changes in disease severity. Out of 11 patients who already gave birth - 63.64% (n = 7) underwent cesarean section. Conclusions: MRgFUS/MR-HIFU seems to be an interesting minimally invasive alternative for women with UFs who wish to conceive and deliver after the procedure. This method does not increase the rate of spontaneous abortions or pregnancy complications. In our opinion, it is important to take off an unjustified badge stating that MRgFUS/MR-HIFU method is contraindicated in women with UFs who wish to conceive.

The outcome of magnetic resonance-guided high-intensity ultrasound for clinically symptomatic submucosal uterine fibroid performed accidentally in very early pregnancy: a case report.

This is a report of an unintended application of MR-HIFU therapy of uterine fibroids (UFs) in a woman in early pregnancy and should be treated as the first description of such an event. A 37-year-old nullipara with confirmed UFs, who suffered from excessive uterine bleeding and dysmenorrhea, was qualified for MR-HIFU therapy to reduce UF-related symptoms. The procedure took place 2 months later. No complications occurred and the patient was discharged home in good overall condition. About 5 weeks after the procedure the patient was diagnosed with viable intrauterine pregnancy. Basing on early pregnancy ultrasound it was calculated that at the time of MR-HIFU procedure the patient was about 10 (+/- 3 days) days after the conception. Later, the pregnancy was uncomplicated and she gave birth to a healthy neonate. Physical examinations did not reveal any abnormalities in her child. Symptoms associated with UFs significantly decreased after the therapy and pregnancy. Despite the fact that the pregnancy being subjected to MR-HIFU treatment had further uncomplicated course, the presented case indicates that counseling/management in women at reproductive age should be standardized to avoid unknown consequences of such unrecommended procedures for the fetus. According to current standards MR-HIFU procedures to treat UFs should never be performed without a negative pregnancy test.

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study.

PURPOSE: Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. METHODS: A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. RESULTS: Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. CONCLUSIONS: Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.

Mechanical fractionation of tissues using microsecond-long HIFU pulses on a clinical MR-HIFU system.

PURPOSE: High intensity focussed ultrasound (HIFU) can non-invasively treat tumours with minimal or no damage to intervening tissues. While continuous-wave HIFU thermally ablates target tissue, the effect of hundreds of microsecond-long pulsed sonications is examined in this work. The objective of this study was to characterise sonication parameter-dependent thermomechanical bioeffects to provide the foundation for future preclinical studies and facilitate clinical translation. METHODS AND MATERIALS: Acoustic power, number of cycles/pulse, sonication time and pulse repetition frequency (PRF) were varied on a clinical magnetic resonance imaging (MRI)-guided HIFU (MR-HIFU) system. Ex vivo porcine liver, kidney and cardiac muscle tissue samples were sonicated (3 × 3 grid pattern, 1 mm spacing). Temperature, thermal dose and T2 relaxation times were quantified using MRI. Lesions were histologically analysed using H&E and vimentin stains for lesion structure and viability. RESULTS: Thermomechanical HIFU bioeffects produced distinct types of fractionated tissue lesions: solid/thermal, paste-like and vacuolated. Sonications at 20 or 60 Hz PRF generated substantial tissue damage beyond the focal region, with reduced viability on vimentin staining, whereas H&E staining indicated intact tissue. Same sonication parameters produced dissimilar lesions in different tissue types, while significant differences in temperature, thermal dose and T2 were observed between the parameter sets. CONCLUSION: Clinical MR-HIFU system was utilised to generate distinct types of lesions and to produce targeted thermomechanical bioeffects in ex vivo tissues. The results guide HIFU research on thermomechanical tissue bioeffects, inform future studies and advice sonication parameter selection for direct tumour ablation or immunomodulation using a clinical MR-HIFU system.

Comparison of Noninvasive High-Intensity Focused Ultrasound with Radiofrequency Ablation of Osteoid Osteoma.

OBJECTIVE: To evaluate clinical feasibility and safety of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) treatment of symptomatic osteoid osteoma and to compare clinical response with standard of care treatment. STUDY DESIGN: Nine subjects with radiologically confirmed, symptomatic osteoid osteoma were treated with MR-HIFU in an institutional review board-approved clinical trial. Treatment feasibility and safety were assessed. Clinical response was evaluated in terms of analgesic requirement, visual analog scale pain score, and sleep quality. Anesthesia, procedure, and recovery times were recorded. This MR-HIFU group was compared with a historical control group of 9 consecutive patients treated with radiofrequency ablation. RESULTS: Nine subjects (7 male, 2 female; 16 ± 6 years) were treated with MR-HIFU without technical difficulties or any serious adverse events. There was significant decrease in their median pain scores 4 weeks within treatment (6 vs 0, P < .01). Total pain resolution and cessation of analgesics were achieved in 8 of 9 patients after 4 weeks. In the radiofrequency ablation group, 9 patients (8 male, 1 female; 10 ± 6 years) were treated in routine clinical practice. All 9 demonstrated complete pain resolution and cessation of medications by 4 weeks with a significant decrease in median pain scores (9 vs 0, P < .001). One developed a second-degree skin burn, but there were no other adverse events. Procedure times and treatment charges were comparable between the 2 groups. CONCLUSION: This pilot study shows that MR-HIFU treatment of osteoid osteoma refractory to medical therapy is feasible and can be performed safely in pediatric patients. Clinical response is comparable with standard of care treatment but without any incisions or exposure to ionizing radiation. TRIAL REGISTRATION: ClinicalTrials.govNCT02349971.

Initial investigation of a novel noninvasive weight loss therapy using MRI-Guided high intensity focused ultrasound (MR-HIFU) of visceral fat.

PURPOSE: MRI-guided high intensity focused ultrasound (MR-HIFU) allows noninvasive heating of deep tissues. Specifically targeting visceral fat deposits with MR-HIFU could offer an effective therapy for reversing the development of obesity, diabetes, and metabolic syndrome. METHODS: Overweight rats received either MR-HIFU of visceral fat, sham treatment, no treatment, or ex vivo temperature calibration. Conventional MR thermometry methods are not effective in fat tissue. Therefore, the T2 of fat was used to estimate heating in adipose tissue. RESULTS: HIFU treated rats lost 7.5% of their body weight 10 days after HIFU, compared with 1.9% weight loss in sham animals (P = 0.008) and 1.3% weight increase in untreated animals (P = 0.004). Additionally, the abdominal fat volume in treated animals decreased by 8.2 mL 7 days after treatment (P = 0.002). The T2 of fat at 1.5 Tesla increased by 3.3 ms per °C. The fat T2 was 103.3 ms before HIFU, but increased to 128.7 ms (P = 0.0005) after HIFU at 70 watts for 16 s and to 131.9 ms (P = 0.0005) after HIFU at 100 watts for 16 s. CONCLUSION: These experiments demonstrate that MR-HIFU of visceral fat could provide a safe, effective, and noninvasive weight loss therapy for combating obesity and the subsequent medical complications. Magn Reson Med 76:282-289, 2016. © 2015 Wiley Periodicals, Inc.

Influence of water and fat heterogeneity on fat-referenced MR thermometry.

PURPOSE: To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. METHODS: Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. RESULTS: The sphere experiment showed susceptibility-related errors of 8.4 °C and 0.2 °C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37 °C was 47.2 ± 21.6 °C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7 °C) yielded a maximum temperature error of 6.6 °C compared with 2.5 °C without fat referencing. CONCLUSION: Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors.

Histopathology of breast cancer after magnetic resonance-guided high-intensity focused ultrasound and radiofrequency ablation.

AIMS: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation and radiofrequency ablation (RFA) are being researched as possible substitutes for surgery in breast cancer patients. The histopathological appearance of ablated tissue has not been studied in great detail. This study aimed to compare histopathological features of breast cancer after MR-HIFU ablation and RFA. METHODS AND RESULTS: MR-HIFU ablation and RFA were performed in- and ex-vivo. Tumours in six mastectomy specimens were partially ablated with RFA or MR-HIFU. In-vivo MR-HIFU ablation was performed 3-6 days before excision; RFA was performed in the operation room. Tissue was fixed in formalin and processed to haematoxylin and eosin (H&E) and cytokeratin-8 (CK-8)-stained slides. Morphology and cell viability were assessed. Ex-vivo ablation resulted in clear morphological changes after RFA versus subtle differences after MR-HIFU. CK-8 staining was decreased or absent. H&E tended to underestimate the size of thermal damage. In-vivo MR-HIFU resulted in necrotic-like changes. Surprisingly, some ablated lesions were CK-8-positive. Histopathology after in-vivo RFA resembled ex-vivo RFA, with hyper-eosinophilic stroma and elongated nuclei. Lesion borders were sharp after MR-HIFU and indistinct after RFA. CONCLUSION: Histopathological differences between MR-HIFU-ablated tissue and RF-ablated tissue were demonstrated. CK-8 was more reliable for cell viability assessment than H&E when used directly after ablation, while H&E was more reliable in ablated tissue left in situ for a few days. Our results contribute to improved understanding of histopathological features in breast cancer lesions treated with minimally invasive ablative techniques.

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

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

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

BACKGROUND: Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. PROCEDURE: Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. RESULTS: Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. CONCLUSIONS: Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors.

Drift correction for accurate PRF-shift MR thermometry during mild hyperthermia treatments with MR-HIFU.

UNLABELLED: There is growing interest in performing hyperthermia treatments with clinical magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) therapy systems designed for tissue ablation. During hyperthermia treatment, however, due to the narrow therapeutic window (41-45 °C), careful evaluation of the accuracy of proton resonant frequency (PRF) shift MR thermometry for these types of exposures is required. PURPOSE: The purpose of this study was to evaluate the accuracy of MR thermometry using a clinical MR-HIFU system equipped with a hyperthermia treatment algorithm. METHODS: Mild heating was performed in a tissue-mimicking phantom with implanted temperature sensors using the clinical MR-HIFU system. The influence of image-acquisition settings and post-acquisition correction algorithms on the accuracy of temperature measurements was investigated. The ability to achieve uniform heating for up to 40 min was evaluated in rabbit experiments. RESULTS: Automatic centre-frequency adjustments prior to image-acquisition corrected the image-shifts in the order of 0.1 mm/min. Zero- and first-order phase variations were observed over time, supporting the use of a combined drift correction algorithm. The temperature accuracy achieved using both centre-frequency adjustment and the combined drift correction algorithm was 0.57° ± 0.58 °C in the heated region and 0.54° ± 0.42 °C in the unheated region. CONCLUSION: Accurate temperature monitoring of hyperthermia exposures using PRF shift MR thermometry is possible through careful implementation of image-acquisition settings and drift correction algorithms. For the evaluated clinical MR-HIFU system, centre-frequency adjustment eliminated image shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.