An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

BACKGROUND: Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. METHODS: The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. RESULTS: At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. CONCLUSIONS: Experimental validation of this new ballistic marker method was performed for liver MRgHIFU ablation, free of any side effects (e.g. no edema around the marker, no infection, no bleeding). The study suggests that the absolute reference marker had ultrasound conspicuity below the detection threshold, was irreversible, MR-compatible and MR-detectable, while also being a well-established histology staining technique.

ARFI-prepared MRgHIFU in liver: simultaneous mapping of ARFI-displacement and temperature elevation, using a fast GRE-EPI sequence.

MR acoustic radiation force imaging (ARFI) is an elegant adjunct to MR-guided high intensity focused ultrasound for treatment planning and optimization, permitting in situ assessment of the focusing and targeting quality. The thermal effect of high intensity focused ultrasound pulses associated with ARFI measurements is recommended to be monitored on line, in particular when the beam crosses highly absorbent structures or interfaces (e.g., bones or air-filled cavities). A dedicated MR sequence is proposed here, derived from a segmented gradient echo-echo planar imaging kernel by adding a bipolar motion encoding gradient with interleaved alternating polarities. Temporal resolution was reduced to 2.1 s, with in-plane spatial resolution of 1 mm. MR-ARFI measurements were executed during controlled animal breathing, with trans-costal successively steered foci, to investigate the spatial modulation of the focus intensity and the targeting offset. ARFI-induced tissue displacement measurements enabled the accurate localization, in vivo, of the high intensity focused ultrasound focal point in sheep liver, with simultaneous monitoring of the temperature elevation. ARFI-based precalibration of the focal point position was immediately followed by trans-costal MR-guided high intensity focused ultrasound ablation, monitored with a conventional proton resonance frequency shift MR thermometry sequence. The latter MR thermometry sequence had spatial resolution and geometrical distortion identical with the ARFI maps, hence no coregistration was required.

A nonparametric temperature controller with nonlinear negative reaction for multi-point rapid MR-guided HIFU ablation.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a noninvasive method for thermal ablation, which exploits the capabilities of magnetic resonance imaging (MRI) for excellent visualization of the target and for near real-time thermometry. Oncological quality of ablation may be obtained by volumetric sonication under automatic feedback control of the temperature. For this purpose, a new nonparametric (i.e., model independent) temperature controller, using nonlinear negative reaction, was designed and evaluated for the iterated sonication of a prescribed pattern of foci. The main objective was to achieve the same thermal history at each sonication point during volumetric MRgHIFU. Differently sized linear and circular trajectories were investigated ex vivo and in vivo using a phased-array HIFU transducer. A clinical 3T MRI scanner was used and the temperature elevation was measured in five slices simultaneously with a voxel size of 1 ×1 ×5 mm(3) and temporal resolution of 4 s. In vivo results indicated a similar thermal history of each sonicated focus along the prescribed pattern, that was 17.3 ± 0.5 °C as compared to 16 °C prescribed temperature elevation. The spatio-temporal control of the temperature also enabled meaningful comparison of various sonication patterns in terms of dosimetry and near-field safety. The thermal build-up tended to drift downwards in the HIFU transducer with a circular scan.

Experimental methods for improved spatial control of thermal lesions in magnetic resonance-guided focused ultrasound ablation.

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU, or MRgFUS) is a hybrid technology that was developed to provide efficient and tolerable thermal ablation of targeted tumors or other pathologic tissues, while preserving the normal surrounding structures. Fast 3-D ablation strategies are feasible with the newly available phased-array HIFU transducers. However, unlike fixed heating sources for interstitial ablation (radiofrequency electrode, microwave applicator, infra-red laser applicator), HIFU uses propagating waves. Therefore, the main challenge is to avoid thermo-acoustical adverse effects, such as energy deposition at reflecting interfaces and thermal drift of the focal lesion toward the near field. We report here our investigations on some novel experimental solutions to solve, or at least to alleviate, these generally known tolerability problems in HIFU-based therapy. Online multiplanar MR thermometry was the main investigational tool extensively used in this study to identify the problems and to assess the efficacy of the tested solutions. We present an improved method to cancel the beam reflection at the exit window (i.e., tissue-to-air interface) by creating a multilayer protection, to dissipate the residual HIFU beam by bulk scattering. This study evaluates selective de-activation of transducer elements to reduce the collateral heating at bone surfaces in the far field, mainly during automatically controlled volumetric ablation. We also explore, using hybrid US/MR simultaneous imaging, the feasibility of using disruptive boiling at the focus, both as a far-field self-shielding technique and as an enhanced ablation strategy (i.e., boiling core controlled HIFU ablation).

Magnetic resonance-guided shielding of prefocal acoustic obstacles in focused ultrasound therapy: application to intercostal ablation in liver.

OBJECTIVES: The treatment of liver cancer is a major public health issue because the liver is a frequent site for both primary and secondary tumors. Rib heating represents a major obstacle for the application of extracorporeal focused ultrasound to liver ablation. Magnetic resonance (MR)-guided external shielding of acoustic obstacles (eg, the ribs) was investigated here to avoid unwanted prefocal energy deposition in the pathway of the focused ultrasound beam. MATERIALS AND METHODS: Ex vivo and in vivo (7 female sheep) experiments were performed in this study. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) was performed using a randomized 256-element phased-array transducer (f∼1 MHz) and a 3-T whole-body clinical MR scanner. A physical mask was inserted in the prefocal beam pathway, external to the body, to block the energy normally targeted on the ribs. The effectiveness of the reflecting material was investigated by characterizing the efficacy of high-intensity focused ultrasound beam reflection and scattering on its surface using Schlieren interferometry. Before high-intensity focused ultrasound sonication, the alignment of the protectors with the conical projections of the ribs was required and achieved in multiple steps using the embedded graphical tools of the MR scanner. Multiplanar near real-time MR thermometry (proton resonance frequency shift method) enabled the simultaneous visualization of the local temperature increase at the focal point and around the exposed ribs. The beam defocusing due to the shielding was evaluated from the MR acoustic radiation force impulse imaging data. RESULTS: Both MR thermometry (performed with hard absorber positioned behind a full-aperture blocking shield) and Schlieren interferometry indicated a very good energy barrier of the shielding material. The specific temperature contrast between rib surface (spatial average) and focus, calculated at the end point of the MRgHIFU sonication, with protectors vs no protectors, indicated an important reduction of the temperature elevation at the ribs' surface, typically by 3.3 ± 0.4 in vivo. This was translated into an exponential reduction in thermal dose by several orders of magnitude. The external shielding covering the full conical shadow of the ribs was more effective when the protectors could be placed close to the ribs' surface and had a tendency to lose its efficiency when placed further from the ribs. Hepatic parenchyma was safely ablated in vivo using this rib-sparing strategy and single-focus independent sonications. CONCLUSIONS: A readily available, MR-compatible, effective, and cost-competitive method for rib protection in transcostal MRgHIFU was validated in this study, using specific reflective strips. The current approach permitted safe intercostal ablation of small volumes (0.7 mL) of liver parenchyma.

Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility study ex vivo.

Magnetic resonance imaging (MRI) and ultrasonography have been used simultaneously in this ex vivo study for the image-guidance of high intensity focused ultrasound (HIFU) treatment in moving tissue. A ventilator-driven balloon produced periodic and non-rigid (i.e. breathing-like) motion patterns in phantoms. MR-compatible ultrasound (US) imaging enabled near real-time 2D motion tracking based on optical flow detection, while near-harmonic reference-free proton resonance frequency shift (PRFS) MR thermometry (MRT) was used to monitor the thermal buildup on line. Reference-free MRT was applied to gradient-echo echo-planar imaging phase maps acquired at the frame rate of 250 to 300 ms/slice with voxel size 1.25×1.25×5 mm(3). The MR-US simultaneous imaging was completely free of mutual interferences while minor RF interferences from the HIFU device were detected in the far field of the US images. The effective duty-cycle of the HIFU sonication was close to 100 % and no off-interval was required to temporally decouple it from the ultrasonography. The motion compensation of the HIFU sonication was achieved with an 8 Hz frame rate and sub-millimeter spatial accuracy, both for single-focus mode and for an iterated multi-foci line scan. Near harmonic reference-less PRFS MRT delivered motion-robust thermal maps perpendicular or parallel to the HIFU beam (0.7 °C precision, 0.5 °C absolute accuracy). Out-of-plane motion compensation was not addressed in this study.

Reference-free PRFS MR-thermometry using near-harmonic 2-D reconstruction of the background phase.

Proton resonance frequency shift (PRFS) MR thermometry (MRT) is the generally preferred method for monitoring thermal ablation, typically implemented with gradient-echo (GRE) sequences. Standard PRFS MRT is based on the subtraction of a temporal reference phase map and is, therefore, intrinsically sensitive to tissue motion (including deformation) and to external perturbation of the magnetic field. Reference-free (or reference-less) PRFS MRT has been previously described by Rieke and was based on a 2-D polynomial fit performed on phase data from outside the heated region, to estimate the background phase inside the region of interest. While their approach was undeniably a fundamental progress in terms of robustness against tissue motion and magnetic perturbations, the underlying mathematical formalism requires a thick unheated border and may be subject to numerical instabilities with high order polynomials. A novel method of reference-free PRFS MRT is described here, using a physically consistent formalism, which exploits mathematical properties of the magnetic field in a homogeneous or near-homogeneous medium. The present implementation requires as input the MR GRE phase values along a thin, nearly-closed and unheated border. This is a 2-D restriction of a classic Dirichlet problem, working on a slice per slice basis. The method has been validated experimentally by comparison with the "ground truth" data, considered to be the standard PRFS method for static ex vivo tissue. "Zero measurement" of the gradient-echo phase baseline was performed in healthy volunteer liver with rapid acquisition (300 ms/image). In vivo data acquired in sheep liver during MR-guided high intensity focused ultrasound (MRgHIFU) sonication were post-processed as proof of applicability in a therapeutic scenario. Bland and Altman mean absolute difference between the novel method and the "ground truth" thermometry in ex vivo static tissue ranged between 0.069 °C and 0.968 °C, compared to the inherent "white" noise SD of 0.23 °C. The accuracy and precision of the novel method in volunteer liver were found to be on average 0.13 °C and respectively 0.65 °C while the inherent "white" noise SD was on average 0.51 °C. The method was successfully applied to large ROIs, up to 6.2 cm inner diameter, and the computing time per slice was systematically less than 100 ms using C++. The current limitations of reference-free PRFS thermometry originate mainly from the need to provide a nearly-closed border, where the MR phase is artifact-free and the tissue is unheated, plus the potential need to reposition that border during breathing to track the motion of the anatomic zone being monitored.A reference-free PRFS thermometry method based on the theoretical framework of harmonic functions is described and evaluated here. The computing time is compatible with online monitoring during local thermotherapy. The current reference-free MRT approach expands the workflow flexibility, eliminates the need for respiratory triggers, enables higher temporal resolution, and is insensitive to unique-event motion of tissue.