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IntroductionCardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms.MethodsWe evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing.ResultsDuring ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group.DiscussionIn conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50′ LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up.

Objective. Ultrafast power Doppler (UPD) is an ultrasound method that can image blood flow at several thousands of frames per second. In particular, the high number of data provided by UPD enables the use of singular value decomposition (SVD) as a clutter filter for suppressing tissue signal. Notably, is has been demonstrated in various applications that SVD filtering increases significantly the sensitivity of UPD to microvascular flows. However, UPD is subjected to significant depth-dependent electronic noise and an optimal denoising approach is still being sought. Approach. In this study, we propose a new denoising method for UPD imaging: the Coherence Factor Mask (CFM). This filter is first based on filtering the ultrasound time-delayed data using SVD in the channel domain to remove clutter signal. Then, a spatiotemporal coherence mask that exploits coherence information between channels for identifying noisy pixels is computed. The mask is finally applied to beamformed images to decrease electronic noise before forming the power Doppler image. We describe theoretically how to filter channel data using a single SVD. Then, we evaluate the efficiency of the CFM filter for denoising in vitro and in vivo images and compare its performances with standard UPD and with three existing denoising approaches. Main results. The CFM filter gives gains in signal-to-noise ratio and contrast-to-noise ratio of up to 22 dB and 20 dB, respectively, compared to standard UPD and globally outperforms existing methods for reducing electronic noise. Furthermore, the CFM filter has the advantage over existing approaches of being adaptive and highly efficient while not requiring a cut-off for discriminating noise and blood signals nor for determining an optimal coherence lag. Significance. The CFM filter has the potential to help establish UPD as a powerful modality for imaging microvascular flows.

In the last decade, a large number of clinical trials have been deployed using Cardiac Magnetic Resonance (CMR) to evaluate cardioprotective strategies aiming at reducing the irreversible myocardial damage at the time of reperfusion. In these studies, segmentation and quantification of myocardial infarct lesion are often performed with a commercial software or an in-house closed-source code development thus creating a barrier for reproducible research. This paper introduces CMRSegTools: an open-source application software designed for the segmentation and quantification of myocardial infarct lesion enabling full access to state-of-the-art segmentation methods and parameters, easy integration of new algorithms and standardised results sharing. This post-processing tool has been implemented as a plug-in for the OsiriX/Horos DICOM viewer leveraging its database management functionalities and user interaction features to provide a bespoke tool for the analysis of cardiac MR images on large clinical cohorts. CMRSegTools includes, among others, user-assisted segmentation of the left-ventricle, semi- and automatic lesion segmentation methods, advanced statistical analysis and visualisation based on the American Heart Association 17-segment model. New segmentation methods can be integrated into the plug-in by developing components based on image processing and visualisation libraries such as ITK and VTK in C++ programming language. CMRSegTools allows the creation of training and testing data sets (labeled features such as lesion, microvascular obstruction and remote ROI) for supervised Machine Learning methods, and enables the comparative assessment of lesion segmentation methods via a single and integrated platform. The plug-in has been successfully used by several CMR imaging studies.

The arrangement of cardiac fibers determines mechanical and electrical properties of the heart and can be altered due to pathology. Hence, the non-invasive assessment of fiber characteristics is of interest from both a pathophysiologic and a diagnostic point of view. Recently, we proposed and validated, by computer simulations, a theoretical framework to have more insight on 3D ultrasound Backscatter Tensor Imaging. The theory showed that spatial coherence (SC) maps of echo signals, across the probe aperture, not only carry information on fiber direction, but also on fiber size and pitch. The aim of this study was to experimentally validate these findings and conduct preliminary in vivo tests. Experiments were conducted on a purposely designed and built phantom consisting of several sets of parallel nylon wires, having different diameter (S) and pitch (P). Finally, preliminary tests were conducted on the biceps of healthy volunteers. Experiments confirmed the simulation results: averaged over all acquisitions, the main-to-secondary lobe distance linearly correlated with P (R2=94%), while the value of the SC at lag 1 (an estimate of the main lobe width) linearly correlated with S (R2=48.6%). In vivo results demonstrated the feasibility of extracting microstructural information of the tissue by the analysis of SC maps.

International audience; 3D fast/ultrasound imaging has emerged in the last years in research but still suffers from its poor image quality. Indeed, using plane/diverge waves does not permit to insonify the medium with sufficient energy at each point to get a good signal-to-noise ratio, contrast-to-noise-ratio or even resolution. On the other hand, coded excitation is currently used to increase signal-to-noise ratio and penetration depth. In this work, the objective is to combine 3D fast/ultrafast imaging with coded excitation to achieve better image quality at a high acquisition rate. Promising experimental results are obtained from both wire and cyst phantoms using a chirp excitation signal. The contrast-to-noise ratio and signal-to-noise ratio were improved by 4 dB and 2 dB respectively by the proposed method in comparison to the conventional way to do 3D imaging using a standard transmit. The improvement of the axial resolution of about 17% is the third important result obtained by the developed method still in comparison with the classical method. Experimental results show that an effective implementation on a research scanner of 3D coded excitation using plane wave imaging is possible.

Sparse arrays represent an alternative to full-gridded arrays in 2-D probes realization. Sparse arrays have been used in B-mode imaging tests, but not in spectral Doppler measurements yet. In this paper, we have investigated, by mean of simulations and experiments, how the use of a sparse array instead of a full-gridded 2-D array impacts on spectral Doppler measurements. A 3 MHz, 1024-element gridded array and a sparse array obtained by properly selecting 256 elements from the full array, have been used to interrogate a parabolic flow. Simulations and experiments highlight that the mean Doppler frequency does not change by using the sparse array instead of the full one. Significant differences appear for the bandwidth (17.2% average bandwidth reduction for the sparse array), and for the signal power (22 dB). Possible explanations of this behavior are discussed. Furthermore, it is shown that the empty lines in the 2-D array impact on the Doppler spectra, leading to sidelobes when steering in the direction perpendicular to such lines.

In the context of acute myocardial infarction, we propose that Low Energy Ultrasound (LEUS) exposures might attenuate the detrimental effects of ischemia and reperfusion injury. Specifically, our goal is to quantify and monitor the effects of ultrasound using an in vitro cardiac cell model of ischemia-reperfusion. The study was conducted using a mono-layer cell model (H9C2 cardiomyoblasts) exposed to a prolonged hypoxia-reoxygenation (HR) challenge. Two groups were formed: i). HR: cells submitted to hypoxia followed by reoxygenation period, and ii). HR+PostCond-LEUS: LEUS applied repeatedly for 20 min starting at the onset of reoxygenation. Cell death was evaluated by flow cytometry for each group at the end of US exposure. Cell viability was clearly improved in the HR+PostCond-LEUS group, at all time points during reoxygenation. This study suggests a potential protective effect of LEUS on cardiomyoblasts exposed to a prolonged hypoxia-reoxygenation insult. More complex in vitro models exploring potential protective mechanisms (SAFE and RISK signaling pathways and in vivo models will be required for a better comprehension of the underlying mechanisms.

The necessity of frame rate enhancement is particularly important in 3D echocardiography since full-volume acquisitions at a quality comparable to 2D imaging require increasing the number of transmissions. Despite the potential of Multi Line Transmission (MLT) in providing high frame rates while preserving the image quality, this method has a non-negligible limitation: the presence of cross-talks artefacts. The objective of this study was to investigate experimentally if cross-talk reduction can be achieved by replacing the typical alignment of the transmissions parallel to the element lines or columns by an alignment along the transverse diagonal of the transducer. The results showed that the diagonal transmission provides a better axial resolution than the linear one. Additionally, as the principal cause of cross-talk artefacts is the interference between the main lobe and the side lobes of parallel transmissions, we measured the values of these lobes in the two cases. The main lobe was up to 5% higher than the side lobe for the linear transmission and up to 25 % higher for the diagonal one. However, the cross talk reduction was achieved with the cost of Contrast to Noise Ratio (CNR), which was three times lower for the diagonal transmission compared to the linear one.

The aim of this paper is to quantitatively investigate the thermal effects generated by the pre-focal interactions of a HIFU beam with a rib cage, in the context of minimally invasive transcostal therapy of liver malignancies.HIFU sonications were produced by a phased-array MR-compatible transducer on Turkey muscle placed on a sheep thoracic cage specimen. The thoracic wall was positioned in the pre-focal zone 3.5 to 6.5 cm below the focus. Thermal monitoring was simultaneously performed using fluoroptic sensors inserted into the medullar cavity of the ribs and high resolution MR-thermometry (voxel: 1 × 1 × 5 mm3, four multi-planar slices).MR-thermometry data indicated nearly isotropic distribution of the thermal energy at the ribs' surface. The temperature elevation at the focus was comparable with the pericostal temperature elevation around unprotected ribs, while being systematically inferior, by more than a factor of four on average, to the intra-medullar values. The spatial profiles of the pericostal and intra-medullar thermal build-up measurements could be smoothly connected using a Gaussian function. The dynamics of the post-sonication thermal relaxation as determined by fluoroptic measurements was demonstrated to be theoretically coherent with the experimental observations.The experimental findings motivate further efforts for the transfer towards clinical routine of effective rib-sparing strategies for hepatic HIFU.

International audience; Background, Motivation and ObjectiveThe emergence of ultrafast imaging allowed new insights into cardiac deformation/motion analysis that enabled new advancements in clinical diagnosis. Several studies showed that a good compromise between the temporal and the spatial resolution can be obtained by transmitting multiple focused beams (MLT) simultaneously. However, the currentimplementation of MLT in 3D cannot be used in dynamic conditions as it was obtained synthetically, by summing the Single Line Transmit (SLT) events before beamforming [Ortega et al., TUFFC, 2016]. The objective of this study is to evaluate for the first time the performance of MLT in 3D ultrasound under dynamic conditions. Statement of Contribution/MethodsThe 3D images were acquired by using four Verasonics research scanners, each of them controlling 8-by-32 elements of a 32-by-32, 3 MHz, Vermon ultrasound transducer. The scan volume was created by stitching 30 triangular sectors (each of angular width = 40°) along the azimuth angular direction. For each triangular sector, 9 transmission events were used for insonifying a full sector by sending simultaneously three focused beams. Thus, the total number of transmissions was 270 corresponding to 27 (elevational) x 30 (azimuthal) focal beams. The Pulse Repetition Frequency (PRF) was set to 2250. Our in vitro model was a tissue mimicking spinning disc having a diameter of 11 cm whose speed could be controlled by a step motor. The disk was placed at approximately 3 cm away from transducer and the image depth was 6.8 cm. Doppler velocities were estimated from the IQ signals using a 2D auto-correlator and a packet length of 7.Results/DiscussionThis study demonstrates the feasibility of Doppler velocity estimation for 3D MLT images. The estimated values presented in the image were in agreement with the expected velocities since the relative mean error was 3.5%. We obtained a three-fold increase in volume rate compared with focus imaging. Analyzing further different MLT/MLA configurations would allow increasing the frequency of volumes and obtaining the optimal compromise between high volume rate and quality color Doppler.

Echocardiography is the most used modality for the evaluation of cardiac function. To obtain a time-resolved volumetric quantification of cardiac motion, ultrafast 3-D imaging is required. Ultrafast ultrasound imaging with diverging waves has demonstrated its potential for clinical 2-D echocardiography. It has been shown that MoCo (motion compensation) strategies based on a triangle transmit arrangement could produce high-contrast cardiac B-mode images at 500 fps [1]. With the purpose of developing high-volume-rate 3-D echocardiography, we introduced a transmit sequence enabling volumetric MoCo for spherical diverging wave imaging.

This work shows the feasibility of performing ultrafast 3D ultrasound imaging by producing diverging waves (DW) with 2D sparse arrays. The 3D volumes were experimentally acquired by individually driving the 1024 elements of a full 32×32 matrix array. The volumes obtained with different sparse configurations were compared to those obtained with two references arrays: the full 32×32 array and a dense array of 716 elements where obtained by de-activating the corner elements of the full array. The comparison criteria were the lateral resolution using the full width at half maximum (FWHM) and the contrast to noise ratio (CNR), measured on the images obtained by scanning a grayscale phantom. The results show that ultrafast 3D ultrasound imaging can be performed with a reduced number of channels using 2D sparse arrays. However, there is still space to find the optimal 2D sparse array configurations to best transmit 3D DWs and potential improvements on image quality may be achieved with dedicated optimization e.g. cost function to homogenize DW wave front.

Ultrafast imaging based on diverging wave (DW) is an active area of research in ultrasound sectorial acquisition because of its capacity of reaching high frame rate. Recently, we have introduced a 3D Fourier-based formalism for the reconstruction of 3D sectorial images with DW insonifications and validated with numerical simulations [Zhang et al. IUS 2016]. The proposed method can provide comparable image quality as DAS but with a much lower computational complexity. This study aims to experimentally verify these theoretical conclusions in vitro.

Echocardiography is one of the most widely spread modality for non-invasive 2-D imaging of the heart. However, to fully observe and quantify left ventricular function and morphology, 3-D imaging is required. The observation of the whole left ventricle remains limited by the temporal resolution of conventional 3-D echocardiography. Indeed, the only way to get wide-angle volumetric images is to merge small scan volumes during inspiratory breath hold. This limitation makes difficult 3D speckle tracking echocardiography. Increasing the temporal resolution with ultrafast 3-D echocardiography could enable imaging of the whole myocardium in a single heartbeat. It has recently been shown that 3-D ultrafast ultrasound imaging is possible with spherical diverging waves emitted by a matrix-array probe. As ultrafast ultrasound requires backscattered signals to be combined coherently, this approach is sensitive to high-velocity tissue motion, especially when the heart is investigated. Ultrafast ultrasound imaging with diverging waves has demonstrated its potential for clinical 2-D-echocardiography only when motion compensation (MoCo) is integrating during the compounding process. It has been demonstrated that MoCo strategies based on a triangle transmit arrangement could produce high-contrast 2-D cardiac B-mode images at 500 fps. In this study, we proposed a feasibility study of high-frame-rate 3-D echocardiography based on an innovative MoCo approach using steered spherical diverging waves. The method was validated in vitro with a rotating disk. The sequences were generated with four Verasonics scanners combined to get 1024 channels and a 3-MHz matrix phased array of 32×32 elements.

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 $1 \times 1 \times 5 \, {\hbox {mm}}^3$ 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 $\pm$ 0.5 $^\circ$ C as compared to 16 $^\circ$ 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.

With the availability of new and more accurate tumour treatment modalities such as high-intensity focused ultrasound or proton therapy, accurate target location prediction has become a key issue. Various approaches for diverse application scenarios have been proposed over the last decade. Whereas external surrogate markers such as a breathing belt work to some extent, knowledge about the internal motion of the organs inherently provides more accurate results. In this paper, we combine a population-based statistical motion model and information from 2d ultrasound sequences in order to predict the respiratory motion of the right liver lobe. For this, the motion model is fitted to a 3d exhalation breath-hold scan of the liver acquired before prediction. Anatomical landmarks tracked in the ultrasound images together with the model are then used to reconstruct the complete organ position over time. The prediction is both spatial and temporal, can be computed in real-time and is evaluated on ground truth over long time scales (5.5 min). The method is quantitatively validated on eight volunteers where the ultrasound images are synchronously acquired with 4D-MRI, which provides ground-truth motion. With an average spatial prediction accuracy of 2.4 mm, we can predict tumour locations within clinically acceptable margins.

Purpose Magnetic resonance-guided high-intensity focused ultrasound is considered to be a promising treatment for localized cancer in abdominal organs such as liver, pancreas, or kidney. Abdominal motion, anatomical arrangement, and required sustained sonication are the main challenges. Methods MR acquisition consisted of thermometry performed with segmented gradient-recalled echo echo-planar imaging, and a segment-based one-dimensional MR navigator parallel to the main axis of motion to track the organ motion. This tracking information was used in real-time for: (i) prospective motion correction of MR thermometry and (ii) HIFU focal point position lock-on target. Ex vivo experiments were performed on a sheep liver and a turkey pectoral muscle using a motion demonstrator, while in vivo experiments were conducted on two sheep liver. Results Prospective motion correction of MR thermometry yielded good signal-to-noise ratio (range, 25 to 35) and low geometric distortion due to the use of segmented EPI. HIFU focal point lock-on target yielded isotropic in-plane thermal build-up. The feasibility of in vivo intercostal liver treatment was demonstrated in sheep. Conclusion The presented method demonstrated in moving phantoms and breathing sheep accurate motion-compensated MR thermometry and precise HIFU focal point lock-on target using only real-time pencil-beam navigator tracking information, making it applicable without any pretreatment data acquisition or organ motion modeling. Magn Reson Med 72:1087–1095, 2014. © 2013 Wiley Periodicals, Inc.

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).

Extracorporeal high-intensity focused ultrasound (HIFU) is a minimally invasive therapy considered with increased interest for the ablation of small tumors in deeply located organs while sparing surrounding critical tissues. A multitude of preclinical and clinical studies have showed the feasibility of the method; however, concurrently they showed several obstacles, among which the management of respiratory motion of abdominal organs is at the forefront. The aim of this review is to describe the different methods that have been proposed for managing respiratory motion and to identify their advantages and weaknesses. First, we specify the characteristics of respiratory motion for the liver, kidneys, and pancreas and the problems it causes during HIFU planning, treatment, and monitoring. Second, we make an inventory of the preclinical and clinical approaches used to overcome the problem of organ motion. Third, we analyze their respective benefits and drawbacks to identify the remaining physical, technological, and clinical challenges. We thereby consider the outlook of motion compensation techniques and those that would be the most suitable for clinical use, particularly under magnetic resonance thermometry monitoring.

Objectives: The combination of ultrasound (US) and magnetic resonance imaging (MRI) may provide a complementary description of the investigated anatomy, together with improved guidance and assessment of image-guided therapies. The aim of the present study was to integrate a clinical setup for simultaneous US and magnetic resonance (MR) acquisition to obtain synchronized monitoring of liver motion. The feasibility of this hybrid imaging and the precision of image fusion were evaluated. Materials and Methods: Ultrasound imaging was achieved using a clinical US scanner modified to be MR compatible, whereas MRI was achieved on 1.5- and 3-T clinical scanners. Multimodal registration was performed between a high-resolution T1 3-dimensional (3D) gradient echo (volume interpolated gradient echo) during breath-hold and a simultaneously acquired 2D US image, or equivalent, retrospective registration of US imaging probe in the coordinate frame of MRI. A preliminary phantom study was followed by 4 healthy volunteer acquisitions, performing simultaneous 4D MRI and 2D US harmonic imaging (Fo = 2.2 MHz) under free breathing. Results: No characterized radiofrequency mutual interferences were detected under the tested conditions with commonly used MR sequences in clinical routine, during simultaneous US/MRI acquisition. Accurate spatial matching between the 2D US and the corresponding MRI plane was obtained during breath-hold. In situ fused images were delivered. Our 4D MRI sequence permitted the dynamic reconstruction of the intra-abdominal motion and the calculation of high temporal resolution motion field vectors. Conclusions: This study demonstrates that, truly, simultaneous US/MR dynamic acquisition in the abdomen is achievable using clinical instruments. A potential application is the US/MR hybrid guidance of high-intensity focused US therapy in the liver.

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.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.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.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.

High intensity focused ultrasound (HIFU) under MRI guidance may provide minimally invasive treatment for localized prostate cancer. In this study, ex vivo and in vivo experiments were performed using a prostate-dedicated endorectal phased array (16 circular elements arranged on a truncated spherical cap of radius 60 mm) and a translation-rotation mechanical actuator in order to evaluate the lesion formation and the potential interest of dual-modality (electronic and mechanical) interleaved displacement of the focus for volumetric sonication paradigms. Different sonication sequences, including elementary lesions, line scan, slice sweeping and volume sonications, were investigated with a clinical 1.5 T MR scanner. Two orthogonal planes (axial and sagittal) were simultaneously monitored using rapid MR thermometry (PRFS method) and the temperature and thermal dose maps were displayed in real time. No RF interferences were detected in MR acquisition during sonications. The shape of the thermal lesions in vivo was examined at day 5 post-treatment by MRI follow-up (T2w sequence and Gd-T1w-TFE) and postmortem histological analysis. This study suggests that electronic displacement of the focus (along the ultrasound propagation axis) interleaved with mechanical X-Z translations and rotation around B(0) can be a suitable modality to treat patient-specific sizes and shapes of a pathologic tissue. The electronic displacement of focus (achieved in less than 0.1 s) is an order of magnitude faster than the mechanical motion of the HIFU device (1 s latency). As an example, for an in vivo volumetric sonication with foci between 32 and 47 mm (7 successive line scans, 11 lines/slice, 4 foci/line) with applied powers between 17.4 and 39.1 Wac, a total duration of sonication of 408.1 s was required to ablate a volume of approximately 5.7 cm(3) (semi-chronic lesion measured at day 5), while the maximum temperature elevation reached was 30 °C. While electronic focusing is necessary to speed up the procedure, one should consider as a potential drawback the non-negligible risk for generating secondary lobes with full steering in 3D. Reference-free PRFS thermometry accurately removed the effects of B(o) dynamic perturbation in the vicinity of the moving transducer. Therefore, the dual-modality volumetric sonication paradigm represents a cost-effective technological compromise to induce the desired shape of the lesion in the prostate through the limited endorectal space, in a reasonable period of time and without side effects.

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.

Purpose: Endocavitary high intensity contact ultrasound (HICU) may offer interesting therapeutic potential for fighting localized cancer in esophageal or rectal wall. On-line MR guidance of the thermotherapy permits both excellent targeting of the pathological volume and accurate preoperatory monitoring of the temperature elevation. In this article, the authors address the issue of the automatic temperature control for endocavitary phased-array HICU and propose a tailor-made thermal model for this specific application. The convergence and stability of the feedback loop were investigated against tuning errors in the controller’s parameters and against input noise, throughex vivo experimental studies and through numerical simulations in which nonlinear response of tissue was considered as expected in vivo. Methods: An MR-compatible, 64-element, cooled-tip, endorectal cylindrical phased-array applicator of contact ultrasound was integrated with fast MR thermometry to provide automatic feedback control of the temperature evolution. An appropriate phase law was applied per set of eight adjacent transducers to generate a quasiplanar wave, or a slightly convergent one (over the circular dimension). A 2D physical model, compatible with on-line numerical implementation, took into account (1) the ultrasound-mediated energy deposition, (2) the heat diffusion in tissue, and (3) the heat sink effect in the tissue adjacent to the tip-cooling balloon. This linear model was coupled to a PID compensation algorithm to obtain a multi-input single-output static-tuning temperature controller. Either the temperature at one static point in space (situated on the symmetry axis of the beam) or the maximum temperature in a user-defined ROI was tracked according to a predefined target curve. The convergence domain in the space of controller’s parameters was experimentally exploredex vivo. The behavior of the static-tuning PID controller was numerically simulated based on a discrete-time iterative solution of the bioheat transfer equation in 3D and considering temperature-dependent ultrasound absorption and blood perfusion. Results: The intrinsic accuracy of the implemented controller was approximately 1% inex vivo trials when providing correct estimates for energy deposition and heat diffusivity. Moreover, the feedback loop demonstrated excellent convergence and stability over a wide range of the controller’s parameters, deliberately set to erroneous values. In the extreme case of strong underestimation of the ultrasound energy deposition in tissue, the temperature tracking curve alone, at the initial stage of the MR-controlled HICU treatment, was not a sufficient indicator for a globally stable behavior of the feedback loop. Our simulations predicted that the controller would be able to compensate for tissue perfusion and for temperature-dependent ultrasound absorption, although these effects were not included in the controller’s equation. The explicit pattern of acoustic field was not required as input information for the controller, avoiding time-consuming numerical operations. Conclusions: The study demonstrated the potential advantages of PID-based automatic temperature control adapted to phased-array MR-guided HICU therapy. Further studies will address the integration of this ultrasound device with a miniature RF coil for high resolution MRI and, subsequently, the experimental behavior of the controllerin vivo.

Real-time image-guided extracorporeal high intensity focused ultrasound (HIFU) has been suggested for minimally invasive treatment of valvular dysfunction in the saphenous vein. Local application of heat on the perimeter of the valve zone was previously reported to induce a partial shrinkage of the collagen, which may correct valvular function. In our study, a novel MR compatible HIFU device has been investigated. This device is based on a non-spherical geometry, with two active elements that create a focusing line which is orthogonal to the beam main axis, aiming to cover the valve longitudinally. The prototype performance was characterized by electro-acoustical measurements of the pressure field and by high-resolution MR thermometry. Pressure and thermal fields were found in good agreement with the theoretical predictions. To investigate the therapeutic potential, fresh samples of excised human veins were filled with an agarose gel, embedded in porcine muscle and exposed to HIFU. The power level applied during a fixed duration of 30 s was varied such that the absolute temperature at focus ranged between 52 degrees C and 83 degrees C. Targeting was achieved under MR guidance using a MR compatible XZ positioning system. A dedicated waterproof miniature loop coil was specifically built to achieve high-resolution MRI image-based targeting (0.25 mm x 0.25 mm x 3 mm voxel) and thermometry (0.4 mm x 0.4 mm x 4 mm voxel). The vein wall was clearly identified on MR images before and after HIFU treatment. The thermal buildup created by the non-spherical transducer could be characterized from MR thermometry data. Shrinkage of the vein wall (above 65 degrees C) was determined by absolute temperature and was not a cumulative thermal dose effect.

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.

Magnetic resonance (MR) imaging and ultrasound (US) imaging are complementary and synergetic noninvasive imaging modalities. US imaging is practically free of geometric distortion and provides high temporal resolution and direct visualization of acoustic obstacles. MR imaging offers excellent tissue contrast and a confirmed method for near-real-time thermometry. Their combination may help increase the intraoperative control and assessment in image-guided therapies. The added value of this dual-modality imaging would consist of a more complete description of the anatomy investigated, more accurate targeting, efficient motion tracking, and reliable immediate assessment of the therapeutic results. This chapter focuses on truly simultaneous US/MR technology integration and early applications. A prototype setup designed to clinical standards is described together with the preliminary evaluation of the hybrid imaging performance in the abdomen. In particular, the precision of image coregistration was assessed in healthy volunteers. Furthermore, a complex study investigated the thermal cavitation effects produced by radio-frequency ablations. Simultaneous US imaging/MR imaging acquisition permitted us to demonstrate that the latter effects induce subsequent magnetic-susceptibility-mediated errors in proton resonance frequency shift thermometry, both in ex vivo models and in patients treated for hepatic malignancies. The foreseen perspectives of the hybrid US imaging/MR imaging technique are included in the final section.

Endocavitary high intensity contact ultrasound (HICU) may offer interesting therapeutic potential for fighting localized cancer in esophageal or rectal wall. On-line MR guidance of the thermotherapy permits both excellent targeting of the pathological volume and accurate preoperatory monitoring of the temperature elevation. In this article, the authors address the issue of the automatic temperature control for endocavitary phased-array HICU and propose a tailor-made thermal model for this specific application. The convergence and stability of the feedback loop were investigated against tuning errors in the controller's parameters and against input noise, through ex vivo experimental studies and through numerical simulations in which nonlinear response of tissue was considered as expected in vivo.An MR-compatible, 64-element, cooled-tip, endorectal cylindrical phased-array applicator of contact ultrasound was integrated with fast MR thermometry to provide automatic feedback control of the temperature evolution. An appropriate phase law was applied per set of eight adjacent transducers to generate a quasiplanar wave, or a slightly convergent one (over the circular dimension). A 2D physical model, compatible with on-line numerical implementation, took into account (1) the ultrasound-mediated energy deposition, (2) the heat diffusion in tissue, and (3) the heat sink effect in the tissue adjacent to the tip-cooling balloon. This linear model was coupled to a PID compensation algorithm to obtain a multi-input single-output static-tuning temperature controller. Either the temperature at one static point in space (situated on the symmetry axis of the beam) or the maximum temperature in a user-defined ROI was tracked according to a predefined target curve. The convergence domain in the space of controller's parameters was experimentally explored ex vivo. The behavior of the static-tuning PID controller was numerically simulated based on a discrete-time iterative solution of the bioheat transfer equation in 3D and considering temperature-dependent ultrasound absorption and blood perfusion.The intrinsic accuracy of the implemented controller was approximately 1% in ex vivo trials when providing correct estimates for energy deposition and heat diffusivity. Moreover, the feedback loop demonstrated excellent convergence and stability over a wide range of the controller's parameters, deliberately set to erroneous values. In the extreme case of strong underestimation of the ultrasound energy deposition in tissue, the temperature tracking curve alone, at the initial stage of the MR-controlled HICU treatment, was not a sufficient indicator for a globally stable behavior of the feedback loop. Our simulations predicted that the controller would be able to compensate for tissue perfusion and for temperature-dependent ultrasound absorption, although these effects were not included in the controller's equation. The explicit pattern of acoustic field was not required as input information for the controller, avoiding time-consuming numerical operations.The study demonstrated the potential advantages of PID-based automatic temperature control adapted to phased-array MR-guided HICU therapy. Further studies will address the integration of this ultrasound device with a miniature RF coil for high resolution MRI and, subsequently, the experimental behavior of the controller in vivo.

The study investigates a new sonication strategy with high-intensity focused ultrasound (HIFU), aiming for improvement of the original Ablatherm procedure in the prostate cancer treatment. The currently implemented and clinically used method (defined as reference) uses a single-element transducer, operated with 60% duty cycle. To implement the novel strategy, the active surface was split into two sectors, which can be powered either sequentially (for temporal switching) or simultaneously (equivalent to a single-element transducer). Numerical simulations were used to predict the lesion shape and to determine for the novel strategy the best set of treatment parameters among the 99 explored cases. The same pattern for the focal point trajectory was executed irrespectively to the sector activating mode. The theoretical duty cycle reached 100% for the sector switching strategy. The HIFU device was built MRI compatible, and consisted of two mirror symmetrical sectors operating at 3 MHz, shaped as a truncated spherical cap. The two sonication strategies were experimentally tested on fresh samples of degassed porcine liver, using fast MR thermometry (proton resonance frequency shift method with voxel size 0.85 x 0.85 x 4.25 mm (3), 2 s/dynamic, 0.5 ( degrees ) C temperature accuracy, two orthogonal slices). A practical value of 87.5% overall duty cycle could be experimentally implemented. The performance of the two sonication strategies was comparatively assessed based on: cumulated thermal dose derived from MR temperature maps, postoperatory MR morphological images sensitive to tissue contrast changes (inversion-recovery T1-weighted turbo spin-echo, voxel size 0.5 x 0.5 x 4 mm (3)) and postoperatory macroscopic tissue examination. Using a sector-switching sonication strategy for prostate cancer treatment-induced lesions of similar size and shape as for the reference approach. When considering the available reserve of duty cycle and the exact lesion size, we concluded the treatment time was reduced by 20% with the new sector switching strategy at equal performance. Further in vivo studies are considered mandatory for preclinical validation.

A new high intensity focused ultrasound (HIFU) probe has been designed and tested by using MRI. The probe is intended to be used by physicians to correct valvular dysfunction in the saphenous vein, which is known to be the cause of superficial venous insufficiency (SVI) and varicose veins. Treating SVI with HIFU is possible, since venous tissue undergoes localized partial shrinkage when subjected to HIFU. In vitro experiments have demonstrated that diameter shrinkage should be sufficient to restore valvular function, as is done in the more aggressive approach known as external valvuloplasty. Numerical simulations and optimization have led to a probe design with two HIFU elements that focus sound uniformly over a line of length 7 mm, at a depth of 15 mm from the skin. A prototype of the probe has been constructed, with a holder that provides space for an MRI-imaging antenna. The probe has been tested by measuring pressure and temperature fields. Results are in good agreement with those predicted by an analytical approach and numerical simulations.

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.