Charles Mougenot

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.

Real‐time adaptive methods for treatment of mobile organs by MRI‐controlled high‐intensity focused ultrasound

Focused ultrasound (US) is a unique and noninvasive technique for local deposition of thermal energy deep inside the body. MRI guidance offers the additional benefits of excellent target visualization and continuous temperature mapping. However, treating a moving target poses severe problems because 1) motion‐related thermometry artifacts must be corrected, 2) the US focal point must be relocated according to the target displacement. In this paper a complete MRI‐compatible, high‐intensity focused US (HIFU) system is described together with adaptive methods that allow continuous MR thermometry and therapeutic US with real‐time tracking of a moving target, online motion correction of the thermometry maps, and regional temperature control based on the proportional, integral, and derivative method. The hardware is based on a 256‐element phased‐array transducer with rapid electronic displacement of the focal point. The exact location of the target during US firing is anticipated using automatic analysis of periodic motions. The methods were tested with moving phantoms undergoing either rigid body or elastic periodical motions. The results show accurate tracking of the focal point. Focal and regional temperature control is demonstrated with a performance similar to that obtained with stationary phantoms. Magn Reson Med 57:319–330, 2007.

Three-dimensional spatial and temporal temperature control with MR thermometry-guided focused ultrasound (MRgHIFU)

High‐intensity focused ultrasound (HIFU) is an efficient noninvasive technique for local heating. Using MRI thermal maps, a proportional, integral, and derivative (PID) automatic temperature control was previously applied at the focal point, or at several points within a plane perpendicular to the beam axis using a multispiral focal point trajectory. This study presents a flexible and rapid method to extend the spatial PID temperature control to three dimensions during each MR dynamic. The temperature in the complete volume is regulated by taking into account the overlap effect of nearby sonication points, which tends to enlarge the heated area along the beam axis. Volumetric temperature control in vitro in gel and in vivo in rabbit leg muscle was shown to provide temperature control with a precision close to that of the temperature MRI measurements. The proposed temperature control ensures heating throughout the volume of interest of up to 1 ml composed of 287 voxels with 95% of the energy deposited within its boundaries and reducing the typical average temperature overshoot to 1°C. Magn Reson Med, 2009.

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 thermometry for monitoring tumor ablation

Local thermal therapies are increasingly used in the clinic for tissue ablation. During energy deposition, the actual tissue temperature is difficult to estimate since physiological processes may modify local heat conduction and energy absorption. Blood flow may increase during temperature increase and thus change heat conduction. In order to improve the therapeutic efficiency and the safety of the intervention, mapping of temperature and thermal dose appear to offer the best strategy to optimize such interventions and to provide therapy endpoints. MRI can be used to monitor local temperature changes during thermal therapies. On-line availability of dynamic temperature mapping allows prediction of tissue death during the intervention based on semi-empirical thermal dose calculations. Much progress has been made recently in MR thermometry research, and some applications are appearing in the clinic. In this paper, the principles of MRI temperature mapping are described with special emphasis on methods employing the temperature dependency of the water proton resonance frequency. Then, the prospects and requirements for widespread applications of MR thermometry in the clinic are evaluated.

Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney.

MR thermometry offers the possibility to precisely guide high‐intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion‐compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR‐guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR‐compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi‐slice, single‐shot, echo‐planar imaging sequence with an update frequency of 2.5 Hz. Motion‐related suceptibility artefacts were compensated for using multi‐baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1°C in kidney and liver, and 2.5°C near the skin. The maximum temperature rise was 30°C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240CEM43) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real‐time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion. Copyright

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.

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.

Non-invasive determination of tissue thermal parameters from high intensity focused ultrasound treatment monitored by volumetric MRI thermometry.

A method is proposed for estimating the perfusion rate, thermal diffusivity, and the absorption coefficient that influence the local temperature during high intensity focused ultrasound (HIFU) thermotherapy procedures. For this purpose, HIFU heating experiments (N = 100) were performed ex vivo on perfused porcine kidney (N = 5) under different flow conditions. The resulting spatio‐temporal temperature variations were measured non‐invasively by rapid volumetric MR‐temperature imaging. The bio‐heat transfer (BHT) model was adapted to describe the spatio‐temporal evolution of tissue temperature in the cortex. Absorption and perfusion coefficients were determined by fitting the integrated thermal load (spatial integration of the thermal maps) curves in time with an analytical solution of the BHT equation proposed for single point HIFU heating. Thermal diffusivity was determined independently by analyzing the spatial spread of the temperature in time during the cooling period. Absorption coefficient and thermal diffusivity were found to be independent of flow, with mean and average values of 11.0 ± 1.85 mm3 · K · J−1 and 0.172 ± 0.003 mm2 · s−1, respectively. A linear dependence of the calculated perfusion rate with flow was observed with a slope of 9.20 ± 0.75 mm−3. The perfusion was found to act as a scaling term with respect to temperature but with no effect on the spatial spread of temperature which only depends on the thermal diffusivity. All results were in excellent agreement with the BHT model, indicating that this model is suitable to predict the evolution of temperature in perfused organs. This quantitative approach allows for determination of tissue thermal parameters with excellent precision (within 10%) and may thus help in quantifying the influence of perfusion during MR guided high intensity focused ultrasound (MRgHIFU). Copyright

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.