Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

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.

Objective. To demonstrate the technical feasibility and the potential interest of using a digital optical camera inside the MR magnet bore for monitoring the breathing cycle and subsequently gating the PRFS MR thermometry, MR-ARFI measurement, and MRgHIFU sonication in the upper abdomen. Materials and Methods. A digital camera was reengineered to remove its magnetic parts and was further equipped with a 7 m long USB cable. The system was electromagnetically shielded and operated inside the bore of a closed 3T clinical scanner. Suitable triggers were generated based on real-time motion analysis of the images produced by the camera (resolution 640×480 pixels, 30 fps). Respiratory-gated MR-ARFI prepared MRgHIFU ablation was performed in the kidney and liver of two sheep in vivo, under general anaesthesia and ventilator-driven forced breathing. Results. The optical device demonstrated very good MR compatibility. The current setup permitted the acquisition of motion artefact-free and high resolution MR 2D ARFI and multiplanar interleaved PRFS thermometry (average SNR 30 in liver and 56 in kidney). Microscopic histology indicated precise focal lesions with sharply delineated margins following the respiratory-gated HIFU sonications. Conclusion. The proof-of-concept for respiratory motion management in MRgHIFU using an in-bore digital camera has been validated in vivo.

A novel architecture for a phased-array high intensity focused ultrasound (HIFU) device was investigated, aiming to increase the capabilities of electronic steering without reducing the size of the elementary emitters. The principal medical application expected to benefit from these developments is the time-effective sonication of large tumours in moving organs. The underlying principle consists of dividing the full array of transducers into multiple sub-arrays of different resonance frequencies, with the reorientation of these individual emitters, such that each sub-array can focus within a given spatial zone. To enable magnetic resonance (MR) compatibility of the device and the number of output channels from the RF generator to be halved, a passive spectral multiplexing technique was used, consisting of parallel wiring of frequency-shifted paired piezoceramic emitters with intrinsic narrow-band response. Two families of 64 emitters (circular, 5 mm diameter) were mounted, with optimum efficiency at 0.96 and 1.03 MHz, respectively. Two different prototypes of the HIFU device were built and tested, each incorporating the same two families of emitters, but differing in the shape of the rapid prototyping plastic support that accommodated the transducers (spherical cap with radius of curvature/aperture of 130 mm/150 mm and, respectively, 80 mm/110 mm). Acoustic measurements, MR-acoustic radiation force imaging (ex vivo) and MR-thermometry (ex vivo and in vivo) were used for the characterization of the prototypes. Experimental results demonstrated an augmentation of the steering range by 80% along one preferentially chosen axis, compared to a classic spherical array of the same total number of elements. The electric power density provided to the piezoceramic transducers exceeded 50 W cm(-2) CW, without circulation of coolant water. Another important advantage of the current approach is the versatility of reshaping the array at low cost.

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.