A 3D high resolution MRI method for the visualization of cardiac fibro-fatty infiltrations.

Modifications of the myocardial architecture can cause abnormal electrical activity of the heart. Fibro-fatty infiltrations have been implicated in various cardiac pathologies associated with arrhythmias and sudden cardiac death, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Here, we report the development of an MRI protocol to observe these modifications at 9.4 T. Two fixed ex vivo human hearts, one healthy and one ARVC, were imaged with an Iterative decomposition with echo asymmetry and least-square estimations (IDEAL) and a magnetization transfer (MT) 3D sequences. The resulting fat fraction and MT ratio (MTR) were analyzed and compared to histological analysis of the three regions ("ARVC triangle") primarily involved in ARVC structural remodeling. In the ARVC heart, high fat content was observed in the "ARVC triangle" and the superimposition of the MTR and fat fraction allowed the identification of fibrotic regions in areas without the presence of fat. The healthy heart exhibited twice less fat than the ARVC heart (31.9%, 28.7% and 1.3% of fat in the same regions, respectively). Localization of fat and fibrosis were confirmed by means of histology. This non-destructive approach allows the investigation of structural remodeling in human pathologies where fibrosis and/or fatty tissue infiltrations are expected to occur.

Quantitative imaging of coronary flows using 3D ultrafast Doppler coronary angiography.

Coronary flow rate remains complex to assess in clinical practice using non-invasive, non-ionizing imaging tools. In this study, we introduce 3D ultrafast Doppler coronary angiography (3D UDCA), an ultrasound-based method to assess coronary blood flows in three-dimensions at high volume-rate and in one single heartbeat. We demonstrate that 3D UDCA can visualize the coronary vasculature with high temporal and spatial resolution and quantify the absolute flow. The feasibility of the technique was demonstrated in an open-chest swine model. The flow rate of the left-anterior descending artery (LAD) assessed by 3D UDCA was reconstructed successfully at the early diastolic and late diastolic phases and was in good agreement with an invasive gold-standard flowmeter during baseline, reactive hyperemia and coronary stenosis (r2 = 0.84). Finally, we demonstrate that a coronary stenosis on the LAD can be visualized as well as its associated flow acceleration.

4D simultaneous tissue and blood flow Doppler imaging: revisiting cardiac Doppler index with single heart beat 4D ultrafast echocardiography.

The goal of this study was to demonstrate the feasibility of semi-automatic evaluation of cardiac Doppler indices in a single heartbeat in human hearts by performing 4D ultrafast echocardiography with a dedicated sequence of 4D simultaneous tissue and blood flow Doppler imaging. 4D echocardiography has the potential to improve the quantification of major cardiac indices by providing more reproducible and less user dependent measurements such as the quantification of left ventricle (LV) volume. The evaluation of Doppler indices, however, did not benefit yet from 4D echocardiography because of limited volume rates achieved in conventional volumetric color Doppler imaging but also because spectral Doppler estimation is still restricted to a single location. High volume rate (5200 volume s-1) transthoracic simultaneous tissue and blood flow Doppler acquisitions of three human LV were performed using a 4D ultrafast echocardiography scanner prototype during a single heartbeat. 4D color flow, 4D tissue Doppler cineloops and spectral Doppler at each voxel were computed. LV outflow tract, mitral inflow and basal inferoseptal locations were automatically detected. Doppler indices were derived at these locations and were compared against clinical 2D echocardiography. Blood flow Doppler indices E (early filling), A (atrial filling), E/A ratio, S (systolic ejection) and cardiac output were assessed on the three volunteers. Simultaneous tissue Doppler indices e' (mitral annular velocity peak), a' (late velocity peak), e'/a' ratio, s' (systolic annular velocity peak), E/e' ratio were also estimated. Standard deviations on three independent acquisitions were averaged over the indices and was found to be inferior to 4% and 8.5% for Doppler flow and tissue Doppler indices, respectively. Comparison against clinical 2D echocardiography gave a p  value larger than 0.05 in average indicating no significant differences. 4D ultrafast echocardiography can quantify the major cardiac Doppler indices in a single heart beat acquisition.

A large aperture row column addressed probe for in vivo 4D ultrafast doppler ultrasound imaging.

Four-dimensional (4D) Ultrafast ultrasound imaging was recently proposed to image and quantify blood flow with high sensitivity in 3D as well as anatomical, mechanical or functional information. In 4D Ultrafast imaging, coherent compounding of tilted planes waves emitted by a 2D matrix array were used to image the medium at high volume rate. 4D ultrafast imaging, however, requires a high channel count (>1000) to drive those probes. Alternative approaches have been proposed and investigated to efficiently reduce the density of elements, such as sparse or under-sampled arrays while maintaining a decent image quality and high volume rate. The row-columns configuration presents the advantage of keeping a large active surface with a low amount of elements and a simple geometry. In this study, we investigate the row and column addressed (RCA) approach with the orthogonal plane wave (OPW) compounding strategy using real hardware limitations. We designed and built a large 7 MHz 128 + 128 probe dedicated to vascular imaging and connected to a 256-channel scanner to implement the OPW imaging scheme. Using this strategy, we demonstrate that 4D ultrafast Power Doppler imaging of a large volume of [Formula: see text] up to [Formula: see text] depth, both in vitro on flow phantoms and in vivo on the carotid artery of a healthy volunteer at a volume rate of 834 Hz.

Self-adaptive ultrasonic beam amplifiers: application to transcostal shock wave therapy.

Ultrasound shock wave therapy is increasingly used for non-invasive surgery. It requires the focusing of very high pressure amplitude in precisely controlled focal spots. In transcostal therapy of the heart or the liver, the high impedance mismatch between the bones and surrounding tissues gives rise to strong aberrations and attenuation of the therapeutic wavefront, with potential risks of injury at the tissue-bone interface. An adaptive propagation of the ultrasonic beam through the intercostal spaces would be required. Several solutions have been developed so far, but they require a prior knowledge of the patient's anatomy or an invasive calibration process, not applicable in clinic. Here, we develop a non-invasive adaptive focusing method for ultrasound therapy through the ribcage using a time reversal cavity (TRC) acting as an ultrasonic beam amplifier. This method is based on ribcage imaging through the TRC and a projection orthogonally to the strongest identified reflectors. The focal pressure of our device was improved by up to 30% using such self-adaptive processing, without degrading the focal spots size and shape. This improvement allowed lesion formation in an Ultracal® phantom through a ribcage without invasive calibration of the device. This adaptive method could be particularly interesting to improve the efficiency and the safety of pulsed cavitational therapy of the heart or the liver.

3D elastic tensor imaging in weakly transversely isotropic soft tissues.

We present herein 3D elastic tensor imaging (3D ETI), an ultrasound-based volumetric imaging technique to provide quantitative volumetric mapping of tissue elastic properties in weakly elastic anistropic media. The technique relies on (1) 4D ultrafast shear wave elastography (SWE) at very high volume rate (e.g. > 8000 Hz, depending only on the imaging depth), (2) a volumetric estimation of shear wave velocity using the eikonal equation and (3) a generalized 3D elastic tensor-based approach. 3D ETI was first evaluated using numerical simulations in homogeneous isotropic and transverse isotropic media. Results showed that 3D ETI can accurately assess tissue stiffness and tissue anisotropy in weakly transversely isotropic media (elastic fractional anisotropy coefficient < 0.34). Experimental feasibility was shown in vitro in a transverse isotropic phantom. Quantification of the elastic properties by 3D ETI was in good agreement with 2D SWE results performed at different orientations using a clinical ultrafast ultrasound scanner. 3D ETI has the potential to provide a volumetric quantitative map of tissue elastic properties in weakly transversely isotropic soft tissues within less than 20 ms of acquisition for the entire imaged volume.

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis. To reproduce venous thrombosis conditions, human whole blood was allowed to clot by stasis in silicone tubes (6 mm internal diameter) at a 30 cm H2O pressure, maintained during the whole experiment. We engineered an ultrasound device composed of dual 2.25 MHz transducers centered around a 6 MHz imaging probe. A therapeutic focus was generated at a 3.2 cm depth from the probe. Thrombotripsy was performed by longitudinally scanning the thrombus at three different speeds: 1 mm s-1 (n = 6); 2 mm s-1 (n = 6); 3 mm s-1 (n = 12). Restored outflow was measured every three passages. Filters were placed to evaluate the debris size. Twenty-four occlusive thrombi, of 2.5 cm mean length and 4.4 kPa mean stiffness, were studied. Flow restoration was systematically obtained by nine subsequent passages (4.5 min maximum). By varying the device's speed, we found an optimal speed of 1 mm s-1 to be efficient for effective recanalization with 90 s (three passages). Within 90 s, flow restoration was of 80, 62 and 74% at respectively 1, 2 and 3 mm s-1. For all groups, cavitation cloud drilled a 1.7 mm mean diameter channel throughout the clot. Debris analysis showed 92% of debris <10 µm, with no fragment > 200 µm.

A semi-analytical model of a time reversal cavity for high-amplitude focused ultrasound applications.

Time reversal cavities (TRC) have been proposed as an efficient approach for 3D ultrasound therapy. They allow the precise spatio-temporal focusing of high-power ultrasound pulses within a large region of interest with a low number of transducers. Leaky TRCs are usually built by placing a multiple scattering medium, such as a random rod forest, in a reverberating cavity, and the final peak pressure gain of the device only depends on the temporal length of its impulse response. Such multiple scattering in a reverberating cavity is a complex phenomenon, and optimisation of the device's gain is usually a cumbersome process, mostly empirical, and requiring numerical simulations with extremely long computation times. In this paper, we present a semi-analytical model for the fast optimisation of a TRC. This model decouples ultrasound propagation in an empty cavity and multiple scattering in a multiple scattering medium. It was validated numerically and experimentally using a 2D-TRC and numerically using a 3D-TRC. Finally, the model was used to determine rapidly the optimal parameters of the 3D-TRC which had been confirmed by numerical simulations.

A finite element model to study the effect of tissue anisotropy on ex vivo arterial shear wave elastography measurements.

Shear wave elastography (SWE) is an ultrasound (US) diagnostic method for measuring the stiffness of soft tissues based on generated shear waves (SWs). SWE has been applied to bulk tissues, but in arteries it is still under investigation. Previously performed studies in arteries or arterial phantoms demonstrated the potential of SWE to measure arterial wall stiffness-a relevant marker in prediction of cardiovascular diseases. This study is focused on numerical modelling of SWs in ex vivo equine aortic tissue, yet based on experimental SWE measurements with the tissue dynamically loaded while rotating the US probe to investigate the sensitivity of SWE to the anisotropic structure. A good match with experimental shear wave group speed results was obtained. SWs were sensitive to the orthotropy and nonlinearity of the material. The model also allowed to study the nature of the SWs by performing 2D FFT-based and analytical phase analyses. A good match between numerical group velocities derived using the time-of-flight algorithm and derived from the dispersion curves was found in the cross-sectional and axial arterial views. The complexity of solving analytical equations for nonlinear orthotropic stressed plates was discussed.

4D in vivo ultrafast ultrasound imaging using a row-column addressed matrix and coherently-compounded orthogonal plane waves.

4D ultrafast ultrasound imaging was recently shown using a 2D matrix (i.e. fully populated) connected to a 1024-channel ultrafast ultrasound scanner. In this study, we investigate the row-column addressing (RCA) matrix approach, which allows a reduction of independent channels from N × N to N + N, with a dedicated beamforming strategy for ultrafast ultrasound imaging based on the coherent compounding of orthogonal plane wave (OPW). OPW is based on coherent compounding of plane wave transmissions in one direction with receive beamforming along the orthogonal direction and its orthogonal companion sequence. Such coherent recombination of complementary orthogonal sequences leads to the virtual transmit focusing in both directions which results into a final isotropic point spread function (PSF). In this study, a 32 × 32 2D matrix array probe (1024 channels), centered at 5 MHz was considered. An RCA array, of same footprint with 32 + 32 elements (64 channels), was emulated by summing the elements either along a line or a column in software prior to beamforming. This approach allowed for the direct comparison of the 32 + 32 RCA scheme to the optimal fully sampled 32 × 32 2D matrix configuration, which served as the gold standard. This approach was first studied through PSF simulations and then validated experimentally on a phantom consisting of anechoic cysts and echogenic wires. The contrast-to-noise ratio and the lateral resolution of the RCA approach were found to be approximately equal to half (in decibel) and twice the values, respectively, obtained when using the 2D matrix approach. Results in a Doppler phantom and the human humeral artery in vivo confirmed that ultrafast Doppler imaging can be achieved with reduced performances when compared against the equivalent 2D matrix. Volumetric anatomic Doppler rendering and voxel-based pulsed Doppler quantification are presented as well. OPW compound imaging using emulated RCA matrix can achieve a power Doppler with sufficient contrast to recover the vein shape and provides an accurate Doppler spectrum.

A 3D time reversal cavity for the focusing of high-intensity ultrasound pulses over a large volume.

Shock wave ultrasound therapy techniques, increasingly used for non-invasive surgery, require extremely high pressure amplitudes in precise focal spots, and large high-power transducers arranged on a spherical shell are usually used to achieve that. This solution allows limited steering of the beam around the geometrical focus of the device at the cost of a large number of transducer elements, and the treatment of large and moving organs like the heart is challenging or impossible. This paper validates numerically and experimentally the possibility of using a time reversal cavity (TRC) for the same purpose. A 128-element, 1 MHz power transducer combined with different multiple scattering media in a TRC was used. We were able to focus high-power ultrasound pulses over a large volume in a controlled manner, with a limited number of transducer elements. We reached sufficiently high pressure amplitudes to erode an Ultracal® target over a 10 cm2 area.

In vivo real-time cavitation imaging in moving organs.

The stochastic nature of cavitation implies visualization of the cavitation cloud in real-time and in a discriminative manner for the safe use of focused ultrasound therapy. This visualization is sometimes possible with standard echography, but it strongly depends on the quality of the scanner, and is hindered by difficulty in discriminating from highly reflecting tissue signals in different organs. A specific approach would then permit clear validation of the cavitation position and activity. Detecting signals from a specific source with high sensitivity is a major problem in ultrasound imaging. Based on plane or diverging wave sonications, ultrafast ultrasonic imaging dramatically increases temporal resolution, and the larger amount of acquired data permits increased sensitivity in Doppler imaging. Here, we investigate a spatiotemporal singular value decomposition of ultrafast radiofrequency data to discriminate bubble clouds from tissue based on their different spatiotemporal motion and echogenicity during histotripsy. We introduce an automation to determine the parameters of this filtering. This method clearly outperforms standard temporal filtering techniques with a bubble to tissue contrast of at least 20 dB in vitro in a moving phantom and in vivo in porcine liver.

Real time shear waves elastography monitoring of thermal ablation: in vivo evaluation in pig livers.

BACKGROUND: Thermal ablation is a widely used minimally invasive treatment modality for different cancers. However, lack of a real-time imaging system for accurate evaluation of the procedure is one of the reasons of local recurrences. Shear waves elastography (SWE) is a new ultrasound (US) imaging modality to quantify tissue stiffness. The aim of the study was to assess the feasibility and accuracy of US elastography for quantitative monitoring of thermal ablation and to determine the elasticity threshold predictive of coagulation necrosis. METHODS: A total of 29 in vivo thermal lesions were performed in pig livers with radiofrequency system. SWE and B-mode images were acquired simultaneously. Liver elasticity was quantified by using SWE data and expressed in kilopascal. After the procedure, pathologic analysis of treated tissues was compared with US images. The sensitivity and positive predictive value of the SWE maps of tissue elasticity were calculated and compared with the boundaries of the pale coagulation necrosis areas found at pathology. RESULTS: The liver mean elasticity values before and after thermal therapy were 6.4 ± 0.3 and 38.1 ± 2.5 kPa, respectively (P < 0.0001). For a threshold of 20 kPa, sensitivity (i.e., the rate of pixels correctly detected as necrosed tissue) was 0.8, and the positive predictive value (i.e., the rate of pixels in the elastographic map >20 kPa that actually developed coagulation necrosis) was 0.83. CONCLUSIONS: Tissue areas with coagulation necrosis are significantly stiffer than the surrounding tissue. SWE permits the real-time detection of coagulation necrosis produced by radiofrequency and could potentially be used to monitor US-guided thermal ablation.

Global approach for transient shear wave inversion based on the adjoint method: a comprehensive 2D simulation study.

Shear wave imaging (SWI) maps soft tissue elasticity by measuring shear wave propagation with ultrafast ultrasound acquisitions (10 000 frames s(-1)). This spatiotemporal data can be used as an input for an inverse problem that determines a shear modulus map. Common inversion methods are local: the shear modulus at each point is calculated based on the values of its neighbour (e.g. time-of-flight, wave equation inversion). However, these approaches are sensitive to the information loss such as noise or the lack of the backscattered signal. In this paper, we evaluate the benefits of a global approach for elasticity inversion using a least-squares formulation, which is derived from full waveform inversion in geophysics known as the adjoint method. We simulate an acoustic waveform in a medium with a soft and a hard lesion. For this initial application, full elastic propagation and viscosity are ignored. We demonstrate that the reconstruction of the shear modulus map is robust with a non-uniform background or in the presence of noise with regularization. Compared to regular local inversions, the global approach leads to an increase of contrast (∼+3 dB) and a decrease of the quantification error (∼+2%). We demonstrate that the inversion is reliable in the case when there is no signal measured within the inclusions like hypoechoic lesions which could have an impact on medical diagnosis.

Arterial wall elasticity: state of the art and future prospects.

Peripheral vascular disease is a frequently occurring disease and is most often caused by atherosclerosis and more rarely by anomalies of the collagen or other components of the arterial wall. Arterial stiffness problems form one of the precursor phenomena of peripheral vascular disease, and in the case of atherosclerosis represents an independent risk marker for the occurrence of cardiovascular disease. The first techniques, developed to evaluate arterial stiffness, use indirect measurements such as pulse wave velocity or the analysis of variations in pressure and volume to estimate arterial wall stiffness. Techniques based on the pulse wave lack precision because they assume that arterial stiffness is uniform throughout the path of the pulse wave, and that it is constant throughout the cardiac cycle. Moreover, measuring the velocity of the pulse wave may be less precise in certain pathological situations: metabolic syndrome, obesity, large chest, mega-dolico artery. Techniques based on the analysis of variations in pressure and in volume do not accurately measure blood pressure, which can only be taken externally. In addition, these techniques require dedicated equipment, which is not reimbursed by the French health care system, and which is cumbersome to use (especially for techniques based on variation in pressure) in clinical practice. This explains why these two techniques are not used in clinical practice. Ultrafast echography is a new ultrasound imaging method that can record up to 10,000 images per second. This high temporal resolution makes it possible to measure the velocity of the local pulse wave and arterial wall stiffness thanks to the remote palpation carried out by shear wave. The ease of use and the accuracy of these two techniques suggest that these diagnostic applications will play a significant role in vascular pathology in the future. It is possible in real time, using a traditional vascular ultrasound probe, to make an accurate assessment of local arterial stiffness and of its variation during the cardiac cycle. This technological breakthrough will probably improve phenotype evaluation of patients suffering from vascular diseases, to more effectively evaluate the cardiovascular risk for patients, at primary and secondary prevention level, and to carry out broad epidemiological studies on cardiovascular risks.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head.

PURPOSE: This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. METHODS: Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. RESULTS: The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. CONCLUSIONS: The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.

Optimal transcostal high-intensity focused ultrasound with combined real-time 3D movement tracking and correction.

Recent studies have demonstrated the feasibility of transcostal high intensity focused ultrasound (HIFU) treatment in liver. However, two factors limit thermal necrosis of the liver through the ribs: the energy deposition at focus is decreased by the respiratory movement of the liver and the energy deposition on the skin is increased by the presence of highly absorbing bone structures. Ex vivo ablations were conducted to validate the feasibility of a transcostal real-time 3D movement tracking and correction mode. Experiments were conducted through a chest phantom made of three human ribs immersed in water and were placed in front of a 300 element array working at 1 MHz. A binarized apodization law introduced recently in order to spare the rib cage during treatment has been extended here with real-time electronic steering of the beam. Thermal simulations have been conducted to determine the steering limits. In vivo 3D-movement detection was performed on pigs using an ultrasonic sequence. The maximum error on the transcostal motion detection was measured to be 0.09 ± 0.097 mm on the anterior-posterior axis. Finally, a complete sequence was developed combining real-time 3D transcostal movement correction and spiral trajectory of the HIFU beam, allowing the system to treat larger areas with optimized efficiency. Lesions as large as 1 cm in diameter have been produced at focus in excised liver, whereas no necroses could be obtained with the same emitted power without correcting the movement of the tissue sample.

Temperature dependence of the shear modulus of soft tissues assessed by ultrasound.

Soft tissue stiffness was shown to significantly change after thermal ablation. To better understand this phenomenon, the study aims (1) to quantify and explain the temperature dependence of soft tissue stiffness for different organs, (2) to investigate the potential relationship between stiffness changes and thermal dose and (3) to study the reversibility or irreversibility of stiffness changes. Ex vivo bovine liver and muscle samples (N = 3 and N = 20, respectively) were slowly heated and cooled down into a thermally controlled saline bath. Temperatures were assessed by thermocouples. Sample stiffness (shear modulus) was provided by the quantitative supersonic shear imaging technique. Changes in liver stiffness are observed only after 45 degrees C. In contrast, between 25 degrees C and 65 degrees C, muscle stiffness varies in four successive steps that are consistent with the thermally induced proteins denaturation reported in the literature. After a 6 h long heating and cooling process, the final muscle stiffness can be either smaller or bigger than the initial one, depending on the stiffness at the end of the heating. Another important result is that stiffness changes are linked to thermal dose. Given the high sensitivity of ultrasound to protein denaturation, this study gives promising prospects for the development of ultrasound-guided HIFU systems.

MR-guided transcranial brain HIFU in small animal models.

Recent studies have demonstrated the feasibility of transcranial high-intensity focused ultrasound (HIFU) therapy in the brain using adaptive focusing techniques. However, the complexity of the procedures imposes provision of accurate targeting, monitoring and control of this emerging therapeutic modality in order to ensure the safety of the treatment and avoid potential damaging effects of ultrasound on healthy tissues. For these purposes, a complete workflow and setup for HIFU treatment under magnetic resonance (MR) guidance is proposed and implemented in rats. For the first time, tissue displacements induced by the acoustic radiation force are detected in vivo in brain tissues and measured quantitatively using motion-sensitive MR sequences. Such a valuable target control prior to treatment assesses the quality of the focusing pattern in situ and enables us to estimate the acoustic intensity at focus. This MR-acoustic radiation force imaging is then correlated with conventional MR-thermometry sequences which are used to follow the temperature changes during the HIFU therapeutic session. Last, pre- and post-treatment magnetic resonance elastography (MRE) datasets are acquired and evaluated as a new potential way to non-invasively control the stiffness changes due to the presence of thermal necrosis. As a proof of concept, MR-guided HIFU is performed in vitro in turkey breast samples and in vivo in transcranial rat brain experiments. The experiments are conducted using a dedicated MR-compatible HIFU setup in a high-field MRI scanner (7 T). Results obtained on rats confirmed that both the MR localization of the US focal point and the pre- and post-HIFU measurement of the tissue stiffness, together with temperature control during HIFU are feasible and valuable techniques for efficient monitoring of HIFU in the brain. Brain elasticity appears to be more sensitive to the presence of oedema than to tissue necrosis.

Non-invasive transcranial ultrasound therapy based on a 3D CT scan: protocol validation and in vitro results.

A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.