Temperature measurement in human fat with T2 imaging.

PURPOSE: To develop a method for noninvasive T2 -based thermometry that enables estimation of the in vivo temperature in adipose tissues at both 1.5T and 3T field strengths. MATERIALS AND METHODS: A total of 27 apparent T2 -temperature measurement sets were performed on 13 human abdominal adipose tissue samples using an inversion prepared dual-echo single-slice sequence for apparent T2 estimation. The measurements were performed on Ingenia 1.5T and 3.0T scanners and Achieva 1.5T and 3.0T scanners. The apparent T2 -values were measured at 4°C temperature intervals during heating from 21 to 45°C and cooling to 21°C. A two-parameter exponential fit was used to estimate the apparent T2 to temperature dependency on a scanner-to-scanner basis. RESULTS: In the temperature range evaluated (21-45°C), the apparent T2 relaxation times increased from an average of ∼100 msec to 190 msec at 1.5T and an average of ∼130 msec to 220 msec at 3T. The measured T2 -relaxation times followed the calibration curve with a median absolute error of 0.37°C and maximum error of 1.7°C in 12 of the 13 samples, with the outlier having a notably different appearance upon visual inspection prior to measurement. CONCLUSION: Changes in apparent T2 relaxation time has the potential to be used for accurately estimating local temperature within in vivo subcutaneous fat.

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.

Uterine fibroids: postsonication temperature decay rate enables prediction of therapeutic responses to MR imaging-guided high-intensity focused ultrasound ablation.

PURPOSE: To determine whether intraprocedural thermal parameters as measured with magnetic resonance (MR) thermometry can be used to predict immediate or delayed therapeutic response after MR-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. MATERIALS AND METHODS: Institutional review board approval and subject informed consent were obtained. A total of 105 symptomatic uterine fibroids (mean diameter, 8.0 cm; mean volume, 251.8 mL) in 71 women (mean age, 43.3 years; age range, 25-52 years) who underwent volumetric MR HIFU ablation were analyzed. Correlations between tumor-averaged intraprocedural thermal parameters (peak temperature, thermal dose efficiency [estimated volume of 240 equivalent minutes at 43°C divided by volume of treatment cells], and temperature decay rate after sonication) and the immediate ablation efficiency (ratio of nonperfused volume [NPV] at immediate follow-up to treatment cell volume) or ablation sustainability (ratio of NPV at 3-month follow-up to NPV at immediate follow-up) were assessed with linear regression analysis. RESULTS: A total of 2818 therapeutic sonications were analyzed. At immediate follow-up with MR imaging (n = 105), mean NPV-to-fibroid volume ratio and ablation efficiency were 0.68 ± 0.26 (standard deviation) and 1.35 ± 0.75, respectively. A greater thermal dose efficiency (B = 1.894, P < .001) and slower temperature decay rate (B = -1.589, P = .044) were independently significant factors that indicated better immediate ablation efficiency. At 3-month follow-up (n = 81), NPV had decreased to 43.1% ± 21.0 of the original volume, and only slower temperature decay rate was significantly associated with better ablation sustainability (B = -0.826, P = .041). CONCLUSION: The postsonication temperature decay rate enables prediction of both immediate and delayed therapeutic responses, whereas thermal dose efficiency enables prediction of immediate therapeutic response to MR HIFU ablation of uterine fibroids.

In vivo T2 -based MR thermometry in adipose tissue layers for high-intensity focused ultrasound near-field monitoring.

PURPOSE: During MR-guided high-intensity focused ultrasound (HIFU) therapy, ultrasound absorption in the near field represents a safety risk and limits efficient energy deposition at the target. In this study, we investigated the feasibility of using T2 mapping to monitor the temperature change in subcutaneous adipose tissue layers. METHODS: The T2 temperature dependence and reversibility was determined for fresh adipose porcine samples. The accuracy was evaluated by comparing T2 -based temperature measurements with probe readings in an ex vivo HIFU experiment. The in vivo feasibility of T2 -based thermometry was studied during HIFU ablations in the liver in pigs and of uterine fibroids in human patients. RESULTS: T2 changed linearly and reversibly with temperature with an average coefficient of 5.2 ± 0.1 ms/°C. For the ex vivo HIFU experiment, the difference between the T2 -based temperature change and the probe temperature was <0.9°C. All in vivo experiments showed temperature-related T2 changes in the near field directly after sonications. As expected, considerable intersubject variations in the cooling times were measured in the in vivo porcine experiments. CONCLUSIONS: The reversibility and linearity of the T2 -temperature dependence of adipose tissue allows for the monitoring of the temperature in the subcutaneous adipose tissue layers.

In vivo optimisation study for multi-baseline MR-based thermometry in the context of hyperthermia using MR-guided high intensity focused ultrasound for head and neck applications.

PURPOSE: In this in vivo study, the feasibility to perform hyperthermia treatments in the head and neck using magnetic resonance image-guided high intensity focused ultrasound (MRgHIFU) was established using a porcine acute model. MATERIALS AND METHODS: Porcine specimens with a weight between 17 and 18 kg were treated in the omohyoid muscle in the neck. Hyperthermia was applied with a target temperature of 41 °C for 30 min using a Sonalleve MRgHIFU system. MR-based thermometry was calculated using water-proton resonance frequency shift and multi-baseline look-up tables indexed by peak-to-peak displacement (Dpp) measurements using a pencil-beam navigator. Three hyperthermia experiments were conducted at different Dpp values of 0.2, 1.0 and 3.0 mm. An optimisation study was carried out to establish the optimal parameters controlling the multi-baseline method that ensured a minimisation of spatial-average peak-to-peak temperature (TSA-pp) and temperature direct current bias (TSA-DC). RESULTS: The multi-baseline technique reduced considerably the noise on both TSA-pp and TSA-DC. The reduction of noise was more important when Dpp was higher. For Dpp = 3 mm the average (±standard deviation (SD)) of TSA-pp and TSA-DC was reduced from 4.5 (± 2.5) and 2.5 (±0.6) °C, respectively, to 0.8 (± 0.7) and 0.09 (± 0.2) °C. CONCLUSIONS: This in vivo study showed the level of noise in PRFS-based thermometry introduced by respiratory motion in the context of MRgHIFU hyperthermia treatment for head and neck and the feasibility of reducing this noise using a multi-baseline technique.

MR thermometry in the human prostate gland at 3.0T for transurethral ultrasound therapy.

PURPOSE: To investigate the spatial, temporal, and temperature resolution of a segmented gradient echo echo-planar imaging (EPI) technique as applied to proton resonance frequency (PRF) shift thermometry at 3 T in the human prostate gland, and to determine appropriate sequence parameters for magnetic resonance imaging (MRI)-controlled transurethral ultrasound thermal therapy. MATERIALS AND METHODS: Eleven healthy volunteers (age range 23-58) were scanned at 3 T with a 16-channel torso coil to study the behavior of a gradient echo EPI thermometry sequence. The temperature stability and geometric distortion were assessed for 11 different parameter sets. In a further five volunteers, the prostate T2* was measured. RESULTS: For all scan parameters investigated, the temperature standard deviation within the prostate was less than 1°C, while the distortion was less than 1 mm. Temperature stability was best with higher TE values (up to 25 msec), larger voxel sizes and lower EPI factors, but this had to be balanced against requirements for good spatial and temporal resolution. Prostate T2* values ranged from 30-50 msec. CONCLUSION: A good balance between temperature stability and temporal/spatial resolution is obtained with TE = 15 msec, voxel size = 1.14 mm, and EPI factor = 9, resulting in a dynamic scan time of 7.2 seconds for the nine slices.

MR thermometry analysis of sonication accuracy and safety margin of volumetric MR imaging-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids.

PURPOSE: To evaluate the accuracy of the size and location of the ablation zone produced by volumetric magnetic resonance (MR) imaging-guided high-intensity focused ultrasound ablation of uterine fibroids on the basis of MR thermometric analysis and to assess the effects of a feedback control technique. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and written informed consent was obtained. Thirty-three women with 38 uterine fibroids were treated with an MR imaging-guided high-intensity focused ultrasound system capable of volumetric feedback ablation. Size (diameter times length) and location (three-dimensional displacements) of each ablation zone induced by 527 sonications (with [n=471] and without [n=56] feedback) were analyzed according to the thermal dose obtained with MR thermometry. Prospectively defined acceptance ranges of targeting accuracy were ±5 mm in left-right (LR) and craniocaudal (CC) directions and ±12 mm in anteroposterior (AP) direction. Effects of feedback control in 8- and 12-mm treatment cells were evaluated by using a mixed model with repeated observations within patients. RESULTS: Overall mean sizes of ablation zones produced by 4-, 8-, 12-, and 16-mm treatment cells (with and without feedback) were 4.6 mm±1.4 (standard deviation)×4.4 mm±4.8 (n=13), 8.9 mm±1.9×20.2 mm±6.5 (n=248), 13.0 mm±1.2×29.1 mm±5.6 (n=234), and 18.1 mm±1.4×38.2 mm±7.6 (n=32), respectively. Targeting accuracy values (displacements in absolute values) were 0.9 mm±0.7, 1.2 mm±0.9, and 2.8 mm±2.2 in LR, CC, and AP directions, respectively. Of 527 sonications, 99.8% (526 of 527) were within acceptance ranges. Feedback control had no statistically significant effect on targeting accuracy or ablation zone size. However, variations in ablation zone size were smaller in the feedback control group. CONCLUSION: Sonication accuracy of volumetric MR imaging-guided high-intensity focused ultrasound ablation of uterine fibroids appears clinically acceptable and may be further improved by feedback control to produce more consistent ablation zones.

High intensity focused ultrasound with large aperture transducers: a MRI based focal point correction for tissue heterogeneity.

PURPOSE: The risk of undesired tissue damage to thoracic cage, heart, and lung during MR guided HIFU ablations of breast cancer can be greatly reduced if a phased array transducer design with a lateral beam direction is used in combination with a large aperture. The disadvantage is an increased sensitivity to focus aberrations due to tissue heterogeneity. Here, the authors propose to restore the focal coherence by using a matched aperture phase correction, which is based on a noninvasively obtained tissue model. METHODS: The method combines high resolution MRI with ultrasound wave measurements of different tissue types to determine a phase correction, which compensates focal point aberrations caused by tissue heterogeneity. 3D segmentation of tissue is used to quantify the relative proportion of each tissue type along a line running from the center of each element of the phased array to the target focal point. RESULTS: For tissue types with a celerity difference of 3%, the proposed method allows to quantify the phase aberration with an accuracy of 6° ± 20° and a correlation factor R(2) = 0.95. Using the refocusing method for a complex heterogeneous phantom resulted in 95% of the maximal pressure, whereas only 70% of the maximal pressure is obtained in absence of any phase correction. CONCLUSIONS: Since the proposed refocusing algorithm is compatible with a standard interventional preplanning and requires only a minimal amount of processing, it presents a promising approach to compensate for aberration in heterogeneous tissues such as the human breast.

Tumour hyperthermia and ablation in rats using a clinical MR-HIFU system equipped with a dedicated small animal set-up.

PURPOSE: We report on the design, performance, and specifications of a dedicated set-up for the treatment of rats on a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system. MATERIALS AND METHODS: The small animal HIFU-compatible 4-channel MR receiver volume coil and animal support were designed as add-on to a clinical 3T Philips Sonalleve MR-HIFU system. Prolonged hyperthermia (T ≈ 42°C, 15 min) and thermal ablation (T = 65°C) was performed in vivo on subcutaneous rat tumours using 1.44 MHz acoustic frequency. The direct treatment effect was assessed with T(2)-weighted imaging and dynamic contrast enhanced (DCE-) MRI as well as histology. RESULTS: The developed HIFU-compatible coil provided an image quality that was comparable to conventional small animal volume coils (i.e. without acoustic window), and a SNR increase by a factor of 10 as compared to the coil set-up used for clinical MR-HIFU therapy. The use of an animal support minimised far field heating and allowed precise regulation of the animal body core temperature, which varied <1°C during treatment. CONCLUSIONS: The results demonstrated that, by using a designated set-up, both controlled hyperthermia and thermal ablation treatment of malignant tumours in rodents can be performed on a clinical MR-HIFU system. This approach provides all the advantages of clinical MR-HIFU, such as volumetric heating, temperature feedback control and a clinical software interface for use in rodent treatment. The use of a clinical system moreover facilitates a rapid translation of the developed protocols into the clinic.

Spectrally selective pencil-beam navigator for motion compensation of MR-guided high-intensity focused ultrasound therapy of abdominal organs.

MR-guided high-intensity focused ultrasound (MR-HIFU) is a noninvasive technique for depositing thermal energy in a controlled manner deep within the body. However, the MR-HIFU treatment of mobile abdominal organs is problematic as motion-related thermometry artifacts need to be corrected and the focal point position must be updated in order to follow the moving organ to avoid damaging healthy tissue. In this article, a fat-selective pencil-beam navigator is proposed for real-time monitoring and compensation of through-plane motion. As opposed to the conventional spectrally nonselective navigator, the fat-selective navigator does not perturb the water-proton magnetization used for proton resonance frequency shift thermometry. This allows the proposed navigator to be placed directly on the target organ for improved motion estimation accuracy. The spectral and spatial selectivity of the proposed navigator pulse is evaluated through simulations and experiments, and the improved slice tracking performance is demonstrated in vivo by tracking experiments on a human kidney and on a human liver. The direct motion estimation provided by the fat-selective navigator is also shown to enable accurate motion compensated MR-HIFU therapy of in vivo porcine kidney, including motion compensation of thermometry and beam steering based on the observed three-dimensional kidney motion.

A method for MRI guidance of intercostal high intensity focused ultrasound ablation in the liver.

PURPOSE: High intensity focused ultrasound (HIFU) is a promising method for the noninvasive treatment of liver tumors. However, the presence of ribs in the HIFU beam path remains problematic since it may lead to adverse effects (skin burns) by absorption and reflection of the incident beam at or near the bone surface. This article presents a method based on magnetic resonance (MR) imaging for identification of the ribs in the HIFU beam, and for selection of the transducer elements to deactivate. METHODS: The ribs are visualized on anatomical images acquired prior to heating and manually segmented. The resulting regions of interest surrounding the ribs are projected onto the transducer surface by ray tracing from the focal point. The transducer elements in the "shadow" of the ribs are then deactivated. The method was validated ex vivo and in vivo in pig liver during breathing under multislice real-time MR thermometry, using the proton resonance frequency shift method. RESULTS: Ex vivo and in vivo temperature data showed that the temperature increase near the ribs was substantial when HIFU sonications were performed with all elements active, whereas the temperature was reduced with deactivation of the transducer elements located in front of the ribs. The temperature at the focal point was similar with and without deactivation of the transducer elements, indicative of no loss of heat efficiency with the proposed technique. CONCLUSIONS: This method is simple, rapid, and reliable, and enables intercostal HIFU ablation while sparing ribs and their surrounding tissues.

Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry.

A volumetric sonication method is proposed that produces volume ablations by steering the focal point along a predetermined trajectory consisting of multiple concentric outward-moving circles. This method was tested in vivo on pig thigh muscle (32 ablations in nine animals). Trajectory diameters were 4, 12, and 16 mm with sonication duration depending on the trajectory size and ranging from 20 to 73 s. Despite the larger trajectories requiring more energy to reach necrosis within the desired volume, the ablated volume per unit applied energy increased with trajectory size, indicating improved treatment efficiency for larger trajectories. The higher amounts of energy required for the larger trajectories also increased the risk of off-focus heating, especially along the beam axis in the near field. To avoid related adverse effects, rapid volumetric multiplane MR thermometry was introduced for simultaneous monitoring of the temperature and thermal dose evolution along the beam axis and in the near field, as well as in the target region with a total coverage of six slices acquired every 3 s. An excellent correlation was observed between the thermal dose and both the nonperfused (R=0.929 for the diameter and R=0.964 for the length) and oedematous (R=0.913 for the diameter and R=0.939 for the length) volumes as seen in contrast-enhanced T1-weighted difference images and T2-weighted postsonication images, respectively. Histology confirmed the presence of a homogeneous necrosis inside the heated volumes. These results show that volumetric high-intensity focused ultrasound (HIFU) sonication allows for efficiently creating large thermal lesions while reducing treatment duration and also that the rapid multiplane MR thermometry improves the safety of the therapeutic procedure by monitoring temperature evolution both inside as well as outside the targeted volume.

High intensity focused ultrasound induced in vivo large volume hyperthermia under 3D MRI temperature control.

PURPOSE: Mild hyperthermia can be used as an adjuvant therapy to enhance radiation therapy or chemotherapy of cancer. However, administering mild hyperthermia is technically challenging due to the high accuracy required of the temperature control. MR guided high-intensity focused ultrasound (MR-HIFU) is a technology that can address this challenge. In this work, accurate and spatially uniform mild hyperthermia is demonstrated for deep-seated clinically relevant heating volumes using a HIFU system under MR guidance. METHODS: Mild hyperthermia heating was evaluated for temperature accuracy and spatial uniformity in 11 in vivo porcine leg experiments. Hyperthermia was induced with a commercial Philips Sonalleve MR-HIFU system embedded in a 1.5T Ingenia MR scanner. The operating software was modified to allow extended duration mild hyperthermia. Heating time varied from 10 min up to 60 min and the assigned target temperature was 42.5 °C. Electronic focal point steering, mechanical transducer movement, and dynamic transducer element switch-off were exploited to enlarge the heated volume and obtain uniform heating throughout the acoustic beam path. Multiple temperature mapping images were used to control and monitor the heating. The magnetic field drift and transducer susceptibility artifacts were compensated to enable accurate volumetric MR thermometry. RESULTS: The obtained mean temperature for the target area (the cross sectional area of the heated volume at focal depth primarily used to control the heating) was on average 42.0 ± 0.6 °C. Temperature uniformity in the target area was evaluated using T10 and T90, which were 43.1 ± 0.6 and 40.9 ± 0.6 °C, respectively. For the near field, the corresponding temperatures were 39.3 ± 0.8 °C (average), 40.6 ± 1.0 °C (T10), and 38.0 ± 0.9 °C (T90). The sonications resulted in a concise heating volume, typically in the shape of a truncated cone. The average depth reached from the skin was 86.9 mm. The results show that the heating algorithm was able to induce deep heating while keeping the near-field temperature uniform and at a safe level. CONCLUSIONS: The capability of MR-HIFU to induce accurate, spatially uniform, and robust mild hyperthermia in large deep-seated volumes was successfully demonstrated through a series of in vivo animal experiments.

Magnetic Resonance-Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation.

PURPOSE: To evaluate the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. METHODS AND MATERIALS: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. RESULTS: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. CONCLUSIONS: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

Magnetic resonance imaging for the exploitation of bubble-enhanced heating by high-intensity focused ultrasound: a feasibility study in ex vivo liver.

Bubble-enhanced heating (BEH) may be exploited to improve the heating efficiency of high-intensity focused ultrasound in liver and to protect tissues located beyond the focal point. The objectives of this study, performed in ex vivo pig liver, were (i) to develop a method to determine the acoustic power threshold for induction of BEH from displacement images measured by magnetic resonance acoustic radiation force imaging (MR-ARFI), and (ii) to compare temperature distribution with MR thermometry for HIFU protocols with and without BEH. The acoustic threshold for generation of BEH was determined in ex vivo pig liver from MR-ARFI calibration curves of local tissue displacement resulting from sonication at different powers. Temperature distributions (MR thermometry) resulting from "conventional" sonications (20 W, 30 s) were compared with those from "composite" sonications performed at identical parameters, but after a HIFU burst pulse (0.5 s, acoustic power over the threshold for induction of BEH). Displacement images (MR-ARFI) were acquired between sonications to measure potential modifications of local tissue displacement associated with modifications of tissue acoustic characteristics induced by the burst HIFU pulse. The acoustic threshold for induction of BEH corresponded to a displacement amplitude of approximately 50 µm in ex vivo liver. The displacement and temperature images of the composite group exhibited a nearly spherical pattern, shifted approximately 4 mm toward the transducer, in contrast to elliptical shapes centered on the natural focal position for the conventional group. The gains in maximum temperature and displacement values were 1.5 and 2, and the full widths at half-maximum of the displacement data were 1.7 and 2.2 times larger than in the conventional group in directions perpendicular to ultrasound propagation axes. Combination of MR-ARFI and MR thermometry for calibration and exploitation of BEH appears to increase the efficiency and safety of HIFU treatment.

Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR-guided high-intensity focused ultrasound mediated mild hyperthermia.

PURPOSE: Ablative hyperthermia (>55 °C) has been used as a definitive treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45 °C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is spatially accurate, with precise and homogeneous heating limited to the target region while also limiting the likelihood of unwanted thermal or mechanical bioeffects (tissue damage, vascular shutoff). Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) can noninvasively heat solid tumors under image-guidance. In a mild hyperthermia setting, a sonication approach utilizing multiple concurrent foci may provide the benefit of reducing acoustic pressure in the focal region (leading to reduced or no mechanical effects), while providing better control over the heating. The objective of this study was to design, implement, and characterize a multifoci sonication approach in combination with a mild hyperthermia heating algorithm, and compare it to the more conventional method of electronically sweeping a single focus. METHODS: Simulations (acoustic and thermal) and measurements (acoustic, with needle hydrophone) were performed. In addition, heating performance of multifoci and single focus sonications was compared using a clinical MR-HIFU platform in a phantom (target = 4-16 mm), in normal rabbit thigh muscle (target = 8 mm), and in a Vx2 tumor (target = 8 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target range = 40.5-41 °C). Data were analyzed for peak acoustic pressure and intensity, heating energy efficiency, temperature accuracy (mean), homogeneity of heating (standard deviation [SD], T10 and T90), diameter and length of the heated region, and thermal dose (CEM(43)). RESULTS: Compared to the single focus approach, multifoci sonications showed significantly lower (67% reduction) peak acoustic pressures in simulations and hydrophone measurements. In a rabbit Vx2 tumor, both single focus and multifoci heating approaches were accurate (mean = 40.82±0.12 °C [single] and 40.70±0.09 °C [multi]) and precise (standard deviation = 0.65±0.05 °C [single] and 0.64±0.04 °C [multi]), producing homogeneous heating (T(10-90) = 1.62 °C [single] and 1.41 °C [multi]). Heated regions were significantly shorter in the beam path direction (35% reduction, p < 0.05, Tukey) for multifoci sonications, i.e., resulting in an aspect ratio closer to one. Energy efficiency was lower for the multifoci approach. Similar results were achieved in phantom and rabbit muscle heating experiments. CONCLUSIONS: A multifoci sonication approach was combined with a mild hyperthermia heating algorithm, and implemented on a clinical MR-HIFU platform. This approach resulted in accurate and precise heating within the targeted region with significantly lower acoustic pressures and spatially more confined heating in the beam path direction compared to the single focus sonication method.The reduction in acoustic pressure and improvement in spatial control suggest that multifoci heating is a useful tool in mild hyperthermia applications for clinical oncology.

MR-guided high-intensity focused ultrasound ablation of breast cancer with a dedicated breast platform.

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Volumetric MR-HIFU ablation of uterine fibroids: role of treatment cell size in the improvement of energy efficiency.

PURPOSE: To evaluate the energy efficiency of differently sized volumetric ablations in MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids. MATERIALS AND METHODS: This study was approved by the institutional review board and informed consent was obtained from all participants. Ten symptomatic uterine fibroids (mean diameter 8.9 cm) in 10 women (mean age 42.2) were treated by volumetric MR-HIFU ablation under binary feedback control. The energy efficiency (mm3/J) of each sonication was calculated as the volume of lethal thermal dose (240 equivalent minutes at 43 °C) per unit acoustic energy applied. Operator-controllable parameters and signal intensity ratio of uterine fibroid to skeletal muscle on T2-weighted MR images were tested with univariate and multivariate analyses to discern which parameters significantly correlated with the ablation energy efficiency. RESULTS: We analyzed a total of 236 sonications. The energy efficiency of the ablations was 0.42±0.25 mm3/J (range 0.004-1.18) with energy efficiency improving with the treatment cell size (4 mm, 0.06±0.06 mm3/J; 8 mm, 0.29±0.12 mm3/J; 12 mm, 0.58±0.18 mm3/J; 16 mm, 0.91±0.17 mm3/J). Treatment cell size (r=0.814, p<0.001), distance of ultrasound propagation (r=-0.151, p=0.020), sonication frequency (1.2 or 1.45 MHz; p<0.001), and signal intensity ratio (r=-0.205, p=0.002) proved to be significant by univariate analysis, while multivariate analysis revealed treatment cell size (B=0.075, p<0.001), US propagation distance (B=-6.928, p<0.001), and signal intensity ratio (B=-0.024, p=0.001) to be independently significant. CONCLUSION: Energy efficiency in volumetric MR-HIFU ablation of uterine fibroids improves with increased treatment cell size, independent of other significant contributors such as distance of ultrasound propagation or signal intensity of the tumor on T2-weighted MR imaging.

Dynamic contrast-enhanced magnetic resonance imaging predicts immediate therapeutic response of magnetic resonance-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids.

OBJECTIVES: : To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in the prediction of the immediate therapeutic response of MR-guided high-intensity focused ultrasound (HIFU) therapy in the treatment of symptomatic uterine fibroids MATERIALS AND METHODS: : Institutional review board approved this study, and informed consent was obtained from all participants. A total of 10 symptomatic uterine fibroids (diameter: mean, 8.9 cm; range, 4.7-12 cm) in 10 female patients (mean age, 42.2 years) were treated with MR-HIFU therapy using the volumetric ablation technique. DCE-MRI and conventional contrast-enhanced MRI were obtained as a baseline and as an immediate follow-up study, respectively. After regions of interest of each treatment cell were properly registered to both MRI studies, DCE-MRI parameters (K, ve, vp) and operator-controllable therapy parameters (power, treatment cell size, sonication depth) were investigated on a cell-by-cell basis to reflect tissue inhomogeneity. Two types of ablation efficacy indices (volume of 240 equivalent minutes at 43°C/treatment-cell volume, nonperfused volume/treatment-cell volume) were then correlated with those parameters using multiple linear regression analysis to determine which factors were significant predictors for ablation efficacy. RESULTS: : We used 293 treatment cells (4 mm, n = 12; 8 mm, n = 115; 12 mm, n = 149; 16 mm, n = 17), and all of them were analyzable. Ablation efficacies were 1.06 ± 0.58 and 0.67 ± 0.39. K (B = -12.035, P < 0.001 and B = -11.516, P < 0.001, respectively) among DCE-MRI parameters and acoustic power (B = 0.008, P < 0.001; B = 0.010, P < 0.001, respectively) among therapy parameters were revealed to be independently significant predictors for both types of ablation efficacy. CONCLUSIONS: : A higher K value at baseline DCE-MRI suggested a poor ablation efficacy of MR-HIFU therapy for symptomatic uterine fibroids.