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Changes in cerebral blood flow are associated with stroke, aneurysms, vascular cognitive impairment, neurodegenerative diseases and other pathologies. Brain angiograms, typically performed via computed tomography or magnetic resonance imaging, are limited to millimetre-scale resolution and are insensitive to blood-flow dynamics. Here we show that ultrafast ultrasound localization microscopy of intravenously injected microbubbles enables transcranial imaging of deep vasculature in the adult human brain at microscopic resolution and the quantification of haemodynamic parameters. Adaptive speckle tracking to correct for micrometric brain-motion artefacts and ultrasonic-wave aberrations induced during transcranial propagation allowed us to map the vascular network of tangled arteries to functionally characterize blood-flow dynamics at a resolution of up to 25 μm and to detect blood vortices in a small deep-seated aneurysm in a patient. Ultrafast ultrasound localization microscopy may facilitate the understanding of brain haemodynamics and of how vascular abnormalities in the brain are related to neurological pathologies.

We extended the capabilities of functional ultrasound to whole-brain four-dimensional (4D) neuroimaging. Our multiplane-wave transmission scheme on matrix arrays at thousands of frames per second provides volumetric recordings of cerebral blood volume changes at high spatiotemporal resolution. We illustrated the approach in rats while providing multiple sensory stimuli, for 4D functional connectivity and during instantaneous tracking of epileptiform events.

Ultrasound localization microscopy can map blood vessels with a resolution much smaller than the wavelength by localizing microbubbles. The current implementations of the technique are limited to 2-D planes or small fields of view in 3-D. These suffer from minute-long acquisitions, out-of-plane microbubbles, and tissue motion. In this paper, we exploit the recent development of 4D ultrafast ultrasound imaging to insonify an isotropic volume up to 20 000 times per second and perform localization microscopy in the three dimensions. Specifically, a 32 ×32 elements, 9-MHz matrix-array probe connected to a 1024-channel programmable ultrasound scanner was used to achieve sub-wavelength volumetric imaging of both the structure and vector flow of a complex 3D structure (a main canal branching out into two side canals). To cope with the large volumes and the need to localize the bubbles in the three dimensions, novel algorithms were developed based on deconvolution of the beamformed microbubble signal. For tracking, individual particles were paired following a Munkres assignment method, and velocimetry was done following a Lagrangian approach. ULM was able to clearly represent the 3-D shape of the structure with a sharp delineation of canal edges (as small as [Formula: see text]) and separate them with a spacing as low as [Formula: see text]. The compounded volume rate of 500 Hz was sufficient to describe velocities in 2.5-150-mm/s range and to reduce the maximum acquisition time to 12 s. This paper demonstrates the feasibility of in vitro 3-D ultrafast ultrasound localization microscopy and opens up the way toward in vivo volumetric ULM.

Pulsed cavitation ultrasound therapy (PCUT) is an effective non-invasive therapeutic approach in various medical indications that relies on the mechanical effects generated by cavitation bubbles. Even though limited by the poor contrast, conventional ultrasound B-Mode imaging has been widely used for the guidance and monitoring of the therapeutic procedure, allowing the visualization of the cavitation bubble cloud. However, the visualization of the bubble cloud is often limited in deep organs such as the liver and the heart and remains moreover completely subjective for the operator. Our goal is to develop a new imaging mode to better identify the cavitation cloud. Active and passive cavitation imaging methods have been developed but none of them has been able to locate the cavitation bubble created by PCUT in real-time and in moving organs. In this paper we propose a passive ultrasound imaging approach combined with a spatiotemporal singular value decomposition filter to detect and map the bubble cloud with high sensitivity and high contrast. In moving applications at a maximal motion speed of 10 mm s -1 , the contrast-to-noise ratio for passive cavitation imaging is up to 10 times higher than for active cavitation imaging, with a temporal resolution of about 100 ms. The mapping of the bubble cloud can be overlaid in real-time to the conventional B-Mode, which permits to locate the cavitation phenomena in relation to the anatomic image. Finally, we extend the technique to volumetric imaging and show its feasibility on moving phantoms.

Patient mortality at one year reaches 90% after out-of-hospital cardiac arrest and resuscitation. Temperature management is one of the main strategies proposed to improve patient outcome after resuscitation and preclinical studies have shown neuroprotective effects when hypothermia is achieved rapidly, although the underlying mechanisms have not yet been elucidated. State-of-the-art brain imaging technologies can bring new insights into the early cerebral events taking place post cardiac arrest and resuscitation. In this paper, we characterized cerebral hemodynamics in a post-cardiac arrest rabbit model using functional ultrasound imaging. Ultrasound datasets were processed to map the dynamic changes in cerebral blood flow and cerebral vascular resistivity with a 10 second repetition rate while animals underwent cardiac arrest and a cardiopulmonary resuscitation. We report that a severe transient hyperemia takes place in the brain within the first twenty minutes post resuscitation, emphasizing the need for fast post-cardiac arrest care. Furthermore, we observed that this early hyperemic event is not spatially homogeneous and that maximal cerebral hyperemia happens in the hippocampus. Finally, we show that rapid cooling induced by total liquid ventilation reduces early cerebral hyperemia, which could explain the improved neurological outcome reported in preclinical studies.

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.

Positron emission tomography-computed tomography (PET-CT) is the most sensitive molecular imaging modality, but it does not easily allow for rapid temporal acquisition. Ultrafast ultrasound imaging (UUI)-a recently introduced technology based on ultrasonic holography-leverages frame rates of up to several thousand images per second to quantitatively map, at high resolution, haemodynamic, biomechanical, electrophysiological and structural parameters. Here, we describe a pre-clinical scanner that registers PET-CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. We demonstrate that PET-CT-UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. Combined anatomical, functional and molecular imaging with PET-CT-UUI represents a high-performance and clinically translatable technology for biomedical research.

Functional neuroimaging modalities are crucial for understanding brain function, but their clinical use is challenging. Recently, the use of ultrasonic plane waves transmitted at ultrafast frame rates was shown to allow for the spatiotemporal identification of brain activation through neurovascular coupling in rodents. Using a customized flexible and noninvasive headmount, we demonstrate in human neonates that real-time functional ultrasound imaging (fUSI) is feasible by combining simultaneous continuous video-electroencephalography (EEG) recording and ultrafast Doppler (UfD) imaging of the brain microvasculature. fUSI detected very small cerebral blood volume variations in the brains of neonates that closely correlated with two different sleep states defined by EEG recordings. fUSI was also used to assess brain activity in two neonates with congenital abnormal cortical development enabling elucidation of the dynamics of neonatal seizures with high spatiotemporal resolution (200 μm for UfD and 1 ms for EEG). fUSI was then applied to track how waves of vascular changes were propagated during interictal periods and to determine the ictal foci of the seizures. Imaging the human brain with fUSI enables high-resolution identification of brain activation through neurovascular coupling and may provide new insights into seizure analysis and the monitoring of brain function., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

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.

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.

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.

We present herein 4D ultrafast ultrasound flow imaging, a novel ultrasound-based volumetric imaging technique for the quantitative mapping of blood flow. Complete volumetric blood flow distribution imaging was achieved through 2D tilted plane-wave insonification, 2D multi-angle cross-beam beamforming, and 3D vector Doppler velocity components estimation by least-squares fitting. 4D ultrafast ultrasound flow imaging was performed in large volumetric fields of view at very high volume rate (>4000 volumes s -1 ) using a 1024-channel 4D ultrafast ultrasound scanner and a 2D matrix-array transducer. The precision of the technique was evaluated in vitro by using 3D velocity vector maps to estimate volumetric flow rates in a vessel phantom. Volumetric Flow rate errors of less than 5% were found when volumetric flow rates and peak velocities were respectively less than 360 ml min -1 and 100 cm s -1 . The average volumetric flow rate error increased to 18.3% when volumetric flow rates and peak velocities were up to 490 ml min -1 and 1.3 m s -1 , respectively. The in vivo feasibility of the technique was shown in the carotid arteries of two healthy volunteers. The 3D blood flow velocity distribution was assessed during one cardiac cycle in a full volume and it was used to quantify volumetric flow rates (375  ±  57 ml min -1 and 275  ±  43 ml min -1 ). Finally, the formation of 3D vortices at the carotid artery bifurcation was imaged at high volume rates.

Objectives: The aim of this study was to investigate the potential of shear wave imaging (SWI), a novel ultrasound-based technique, to noninvasively quantify passive diastolic myocardial stiffness in an ovine model of ischemic cardiomyopathy., Background: Evaluation of diastolic left ventricular function is critical for evaluation of heart failure and ischemic cardiomyopathy. Myocardial stiffness is known to be an important property for the evaluation of the diastolic myocardial function, but this parameter cannot be measured noninvasively by existing techniques., Methods: SWI was performed in vivo in open-chest procedures in 10 sheep. Ligation of a diagonal of the left anterior descending coronary artery was performed for 15 min (stunned group, n = 5) and 2 h (infarcted group, n = 5). Each procedure was followed by a 40-min reperfusion period. Diastolic myocardial stiffness was measured at rest, during ischemia, and after reperfusion by using noninvasive shear wave imaging. Simultaneously, end-diastolic left ventricular pressure and segmental strain were measured with a pressure catheter and sonomicrometers during transient vena caval occlusions to obtain gold standard evaluation of myocardial stiffness using end-diastolic strain-stress relationship (EDSSR)., Results: In both groups, the end-systolic circumferential strain was drastically reduced during ischemia (from 14.2 ± 1.2% to 1.3 ± 1.6% in the infarcted group and from 13.5 ± 3.0% to 1.9 ± 1.8% in the stunned group; p <0.01). SWI diastolic stiffness increased after 2 h of ischemia from 1.7 ± 0.4 to 6.2 ± 2.2 kPa (p < 0.05) and even more after reperfusion (12.1 ± 4.2 kPa; p < 0.01). Diastolic myocardial stiffening was confirmed by the exponential constant coefficient of the EDSSR, which increased from 8.8 ± 2.3 to 25.7 ± 9.5 (p < 0.01). In contrast, SWI diastolic stiffness was unchanged in the stunned group (2.3 ± 0.4 kPa vs 1.8 ± 0.3 kPa, p = NS) which was confirmed also by the exponential constant of EDSSR (9.7 ± 3.1 vs 10.2 ± 2.3, p = NS)., Conclusions: Noninvasive SWI evaluation of diastolic myocardial stiffness can differentiate between stiff, noncompliant infarcted wall and softer wall containing stunned myocardium., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We have previously proven the feasibility of ultrasound-based shear wave imaging (SWI) to non-invasively characterize myocardial fiber orientation in both in vitro porcine and in vivo ovine hearts. The SWI-estimated results were in good correlation with histology. In this study, we proposed a new and robust fiber angle estimation method through a tensor-based approach for SWI, coined together as elastic tensor imaging (ETI), and compared it with magnetic resonance diffusion tensor imaging (DTI), a current gold standard and extensively reported non-invasive imaging technique for mapping fiber architecture. Fresh porcine (n = 5) and ovine (n = 5) myocardial samples (20 × 20 × 30 mm³) were studied. ETI was firstly performed to generate shear waves and to acquire the wave events at ultrafast frame rate (8000 fps). A 2.8 MHz phased array probe (pitch = 0.28 mm), connected to a prototype ultrasound scanner, was mounted on a customized MRI-compatible rotation device, which allowed both the rotation of the probe from -90° to 90° at 5° increments and co-registration between two imaging modalities. Transmural shear wave speed at all propagation directions realized was firstly estimated. The fiber angles were determined from the shear wave speed map using the least-squares method and eigen decomposition. The test myocardial sample together with the rotation device was then placed inside a 7T MRI scanner. Diffusion was encoded in six directions. A total of 270 diffusion-weighted images (b = 1000 s mm⁻², FOV = 30 mm, matrix size = 60 × 64, TR = 6 s, TE = 19 ms, 24 averages) and 45 B₀ images were acquired in 14 h 30 min. The fiber structure was analyzed by the fiber-tracking module in software, MedINRIA. The fiber orientation in the overlapped myocardial region which both ETI and DTI accessed was therefore compared, thanks to the co-registered imaging system. Results from all ten samples showed good correlation (r² = 0.81, p < 0.0001) and good agreement (3.05° bias) between ETI and DTI fiber angle estimates. The average ETI-estimated fractional anisotropy (FA) values decreased from subendocardium to subepicardium (p < 0.05, unpaired, one-tailed t-test, N = 10) by 33%, whereas the corresponding DTI-estimated FA values presented a change of -10% (p > 0.05, unpaired, one-tailed t-test, N = 10). In conclusion, we have demonstrated that the fiber orientation estimated by ETI, which assesses the shear wave speed (and thus the stiffness), was comparable to that measured by DTI, which evaluates the preferred direction of water diffusion, and have validated this concept within the myocardium. Moreover, ETI was shown capable of mapping the transmural fiber angles with as few as seven shear wave propagation directions.

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.

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is currently hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to a precise mapping of the lesion. HIFU treatment and monitoring were respectively performed using a confocal setup consisting of a 2.5-MHz single element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Ultrasound-based strain imaging was combined with shear wave imaging on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created with pushing beams of 100 μs at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real-time monitoring of the treatment. When thermal damage occurs, tissue stiffness was found to increase up to 4-fold and strain imaging showed strong shrinkages that blur the temperature information. We show that strain imaging elastograms are not easy to interpret for accurate lesion characterization, but SWI provides a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave thermometry (SWT) developed in the companion paper allows mapping temperature with the same method. Combined SWT and shear wave imaging can map the lesion stiffening and temperature outside the lesion, which could be used to predict the eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be robust to motion and reliable in vivo on sheep muscle.

The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. To monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume using the same multi-element probe. Bubble nucleation was induced using a focused transducer (660 kHz, f-number = 1) driven by a high-power electric burst (up to 300 W) of one to two cycles. Detection was performed with a linear array (4 to 7 MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unnucleated medium. These indicated the appearance of stable cavitating regions. Because of the ultrafast frame rate, active detection occurred as quickly as 330 μs after the high-amplitude excitation and the dynamics of the induced regions were studied individually.

Adaptive focusing of ultrasonic waves under the guidance of a magnetic resonance (MR) system is demonstrated for medical applications. This technique is based on the maximization of the ultrasonic wave intensity at one targeted point in space. The wave intensity is indirectly estimated from the local tissue displacement induced at the chosen focus by the acoustic radiation force of ultrasonic beams. Coded ultrasonic waves are transmitted by an ultrasonic array and an MRI scanner is used to measure the resulting local displacements through a motion-sensitive MR sequence. After the transmission of a set of spatially encoded ultrasonic waves, a non-iterative inversion process is employed to accurately estimate the spatial-temporal aberration induced by the propagation medium and to maximize the acoustical intensity at the target.Both programmable and physical aberrating layers introducing strong distortions (up to 2pi radians) were recovered within acceptable errors (<0.8 rad). This noninvasive technique is shown to accurately correct phase aberrations in a phantom gel with negligible heat deposition and limited acquisition time. These refocusing performances demonstrate a major potential in the field of MR-guided ultrasound therapy in particular for transcranial brain high-intensity focused 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.

An aberration correction method based on the maximization of the wave intensity at the focus of an emitting array is presented. The potential of this new adaptive focusing technique is investigated for ultrasonic focusing in biological tissues. The acoustic intensity is maximized noninvasively through direct measurement or indirect estimation of the beam energy at the focus for a series of spatially coded emissions. For ultrasonic waves, the acoustic energy at the desired focus can be indirectly estimated from the local displacements induced in tissues by the ultrasonic radiation force of the beam. Based on the measurement of these displacements, this method allows determination of the precise estimation of the phase and amplitude aberrations, and consequently the correction of aberrations along the beam travel path. The proof of concept is first performed experimentally using a large therapeutic array with strong electronic phase aberrations (up to 2pi). Displacements induced by the ultrasonic radiation force at the desired focus are indirectly estimated using the time shift of backscattered echoes recorded on the array. The phase estimation is deduced accurately using a direct inversion algorithm which reduces the standard deviation of the phase distribution from sigma = 1.89 radian before correction to sigma = 0.53 radian following correction. The corrected beam focusing quality is verified using a needle hydrophone. The peak intensity obtained through the aberrator is found to be -7.69 dB below the reference intensity obtained without any aberration. Using the phase correction, a sharp focus is restored through the aberrator with a relative peak intensity of -0.89 dB. The technique is tested experimentally using a linear transmit/receive array through a real aberrating layer. The array is used to automatically correct its beam quality, as it both generates the radiation force with coded excitations and indirectly estimates the acoustic intensity at the focus with speckle tracking. This technique could have important implications in the field of high-intensity focused ultrasound even in complex configurations such as transcranial, transcostal, or deep seated organs.

A method for tracking locally the 3D motion of biological tissues is developed and applied to the correction of motion during high intensity focused ultrasound (HIFU) therapy. The motion estimation technique is based on an accurate ultrasonic speckle tracking method. A pulse-echo sequence is performed for a subset of the transducers of a phased array. For each of these sub-apertures, the displacement is estimated by computing the 1D cross-correlation of the backscattered signals acquired at two consecutive times. The local 3D motion vector is then computed using a inversion algorithm. This technique is experimentally validated in vivo on anesthetized pigs. The 3D motion of liver tissues is tracked in real-time. The technique is combined with HIFU sequences and a real-time feedback correction of the HIFU beam is achieved by adjusting the delays of each channel. The sonications "locked on target" are interleaved with very motion estimation sequences.

The feasibility of temperature estimation during high-intensity focused ultrasound therapy using pulse-echo diagnostic ultrasound data has been demonstrated. This method is based upon the measurement of thermally-induced modifications in backscattered RF echoes due to thermal expansion and local changes in the speed of sound. It has been shown that strong ripple artifacts due to the thermo-acoustic lens effect severely corrupt the temperature estimates behind the heated region. We propose here a new imaging technique that improves the temperature estimation behind the heated region and reduces the variance of the temperature estimates in the entire image. We replaced the conventional beamforming on transmit with multiple steered plane wave insonifications using several subapertures. A two-dimensional temperature map is estimated from axial displacement maps between consecutive RF images of identically steered plane wave insonifications. Temperature estimation is then improved by averaging the two-dimensional maps from the multiple steered plane wave insonifications. Experiments were conducted in a tissue-mimicking gelatin-based phantom and in fresh bovine liver.

Thermally-induced lesions are generally stiffer than surrounding tissues. We propose here to use the supersonic shear imaging technique (SSI) for monitoring high-intensity focused ultrasound (HIFU) therapy. This new elasticity imaging technique is based on remotely creating shear sources using an acoustic radiation force at different locations in the medium. In these experiments, an HIFU probe is used to generate lesions in fresh tissue samples. A diagnostic transducer, controlled by our ultrafast scanner, is located in the therapeutic probe focal plane. It is used for both generating the shear waves and imaging the resulting propagation at frame rates reaching 5,000 images/s. Movies of the shear wave propagation can be computed off-line. The therapeutic and imaging sequences are interleaved and a set of wave propagation movies is performed during the heating process. From each movie, elasticity estimations have been performed using an inversion algorithm. It demonstrates the feasibility of detecting and quantifying the hardness of HIFU-induced lesions using SSI.