Max O. Köhler

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.

Improved Volumetric MR-HIFU Ablation by Robust Binary Feedback Control

Volumetric high-intensity focused ultrasound (HIFU) guided by multiplane magnetic resonance (MR) thermometry has been shown to be a safe and efficient method to thermally ablate large tissue volumes. However, the induced temperature rise and thermal lesions show significant variability, depending on exposure parameters, such as power and timing, as well as unknown tissue parameters. In this study, a simple and robust feedback-control method that relies on rapid MR thermometry to control the HIFU exposure during heating is introduced. The binary feedback algorithm adjusts the durations of the concentric ablation circles within the target volume to reach an optimal temperature. The efficacy of the binary feedback control was evaluated by performing 90 ablations in vivo and comparing the results with simulations. Feedback control of the sonications improved the reproducibility of the induced lesion size. The standard deviation of the diameter was reduced by factors of 1.9, 7.2, 5.0, and 3.4 for 4-, 8-, 12-, and 16-mm lesions, respectively. Energy efficiency was also improved, as the binary feedback method required less energy to create the desired lesion. These results show that binary feedback improves the quality of volumetric ablation by consistently producing thermal lesions of expected size while reducing the required energy as well.

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.

Quantification of near‐field heating during volumetric MR‐HIFU ablation

PURPOSE High-intensity focused ultrasound guided by magnetic resonance imaging has been extensively evaluated during the past decade as a clinical alternative for thermal ablation of tumor tissue. However, the maximal ablation volume is limited by the extensive treatment duration resulting from the small size of the focal point as compared to the average tumor size. Volumetric sonication has been shown to efficiently enlarge the ablated volume per sonication, but remains limited by the temperature increase induced in the skin and fat layers. In this study, multiplane MR thermometry is proposed for monitoring the near-field temperature rise in order to prevent related unintended thermal damage. METHODS The method was evaluated by performing sonications in the thigh muscle of 11 pigs maintained under general anesthesia. Volumetric ablations were performed by steering the focal point along trajectories consisting of multiple outward-moving concentric circles. Near-field heating was characterized with MR temperature maps and thermal dose maps. The results from the MR measurements were compared to simulations. RESULTS In this study, the measured maximum temperature rise was found to correlate linearly with the surface energy density within the near field of the beam path with a slope of 4.2 K mm2/J. This simple linear model appears to be almost independent of the trajectory pattern and the sonication depth. The safety limit to avoid lethal damage of the subcutaneous tissues of the porcine thigh was identified to be an absolute temperature of 50 degrees C, corresponding to a surface energy density of 2.5 J/mm2 at 1.2 MHz. CONCLUSIONS A linear relationship can be established to estimate the temperature increase based on the chosen power prior to ablation, thereby providing an a priori safety check for possible excessive near-field heating using a known surface energy density threshold. This method would also give the clinician the possibility to abort the sonication should excessive near-field temperature rise be seen before fat layer damage or skin burns are inflicted.

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 (Ktrans, 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. Ktrans (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 Ktrans value at baseline DCE-MRI suggested a poor ablation efficacy of MR-HIFU therapy for symptomatic uterine fibroids.

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 T2‐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.

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

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.

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.

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. Magn Reson Med, 2011.