Curved toroidal row column addressed transducer for 3D ultrafast ultrasound imaging.

3D Imaging of the human heart at high frame rate is of major interest for various clinical applications. Electronic complexity and cost has prevented the dissemination of 3D ultrafast imaging into the clinic. Row column addressed (RCA) transducers provide volumetric imaging at ultrafast frame rate by using a low electronic channel count, but current models are ill-suited for transthoracic cardiac imaging due to field-of-view limitations. In this study, we proposed a mechanically curved RCA with an aperture adapted for transthoracic cardiac imaging (24 × 16 mm²). The RCA has a toroidal curved surface of 96 elements along columns (curvature radius rC = 4.47 cm) and 64 elements along rows (curvature radius rR = 3 cm). We implemented delay and sum beamforming with an analytical calculation of the propagation of a toroidal wave which was validated using simulations (Field II). The imaging performance was evaluated on a calibrated phantom. Experimental 3D imaging was achieved up to 12 cm deep with a total angular aperture of 30° for both lateral dimensions. The Contrast-to-Noise ratio increased by 12 dB from 2 to 128 virtual sources. Then, 3D Ultrasound Localization Microscopy (ULM) was characterized in a sub-wavelength tube diameter. Finally, 3D ULM was demonstrated on a perfused ex-vivo swine heart to image the coronary microcirculation.

Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept study.

BACKGROUND: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10 µm). In this study, we developed an approach to image alterations of the microvascular coronary flow in ex vivo perfused swine hearts. METHODS: A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. FINDINGS: We were able to image the coronary microcirculation of ex vivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10 mm/s in arterioles up to more than 200 mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31 ± 11 mm/s at 87 mmHg to 47 ± 17 mm/s at 132 mmHg (N = 3 hearts, P < 0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204 ± 305 MB/mm2 compared to 3182 ± 1302 MB/mm2 in the surrounding re-perfused area. INTERPRETATION: We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. FUNDING: This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement.

3D Quasi-Static Ultrasound Elastography With Plane Wave In Vivo.

In biological tissue, an increase in elasticity is often a marker of abnormalities. Techniques such as quasi-static ultrasound elastography have been developed to assess the strain distribution in soft tissues in two dimensions using a quasi-static compression. However, as abnormalities can exhibit very heterogeneous shapes, a three dimensional approach would be necessary to accurately measure their volume and remove operator dependency. Acquisition of volumes at high rates is also critical to performing real-time imaging with a simple freehand compression. In this study, we developed for the first time a 3D quasi-static ultrasound elastography method with plane waves that estimates axial strain distribution in vivo in entire volumes at high volume rate. Acquisitions were performed with a 2D matrix array probe of 2.5MHz frequency and 256 elements. Plane waves were emitted at a volume rate of 100 volumes/s during a continuous motorized and freehand compression. 3D B-mode volumes and 3D cumulative axial strain volumes were successfully estimated in inclusion phantoms and in ex vivo canine liver before and after a high intensity focused ultrasound ablation. We also demonstrated the in vivo feasibility of the method using freehand compression on the calf muscle of a human volunteer and were able to retrieve 3D axial strain volume at a high volume rate depicting the differences in stiffness of the two muscles which compose the calf muscle. 3D ultrasound quasi-static elastography with plane waves could become an important technique for the imaging of the elasticity in human bodies in three dimensions using simple freehand scanning.

Assessment of Takayasu's arteritis activity by ultrasound localization microscopy.

BACKGROUND: Ultrasound localization microscopy (ULM) based on ultrafast ultrasound imaging of circulating microbubbles (MB) can image microvascular blood flows in vivo up to the micron scale. Takayasu arteritis (TA) has an increased vascularisation of the thickened arterial wall when active. We aimed to perform vasa vasorum ULM of the carotid wall and demonstrate that ULM can provide imaging markers to assess the TA activity. METHODS: Patients with TA were consecutively included with assessment of activity by the National Institute of Health criteria: 5 had active TA (median age 35.8 [24.5-46.0] years) and 11 had quiescent TA (37.2 [31.7-47.3] years). ULM was performed using a 6.4 MHz probe and a dedicated imaging sequence (plane waves with 8 angles, frame rate 500 Hz), coupled with the intravenous injection of MB. Individual MB were localised at a subwavelength scale then tracked, allowing the reconstruction of the vasa vasorum flow anatomy and velocity. FINDINGS: ULM allowed to show microvessels and to measure their flow velocity within the arterial wall. The number of MB detected per second in the wall was 121 [80-146] in active cases vs. 10 [6-15] in quiescent cases (p = 0.0005), with a mean velocity of 40.5 [39.0-42.9] mm.s-1 in active cases. INTERPRETATION: ULM allows visualisation of microvessels within the thickened carotid wall in TA, with significantly greater MB density in active cases. ULM provides a precise visualisation in vivo of the vasa vasorum and gives access to the arterial wall vascularisation quantification. FUNDING: French Society of Cardiology. ART (Technological Research Accelerator) biomedical ultrasound program of INSERM, France.

Transcranial 3D ultrasound localization microscopy using a large element matrix array with a multi-lens diffracting layer: anin vitrostudy.

Objective. Early diagnosis and acute knowledge of cerebral disease require to map the microflows of the whole brain. Recently, ultrasound localization microscopy (ULM) was applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale. Whole brain 3D clinical ULM remains challenging due to the transcranial energy loss which reduces significantly the imaging sensitivity.Approach. Large aperture probes with a large surface can increase both the field of view and sensitivity. However, a large active surface implies thousands of acoustic elements, which limits clinical translation. In a previous simulation study, we developed a new probe concept combining a limited number of elements and a large aperture. It is based on large elements, to increase sensitivity, and a multi-lens diffracting layer to improve the focusing quality. In this study, a 16 elements prototype, driven at 1 MHz frequency, was made andin vitroexperiments were performed to validate the imaging capabilities of this new probe concept.Main results. First, pressure fields emitted from a large single transducer element without and with diverging lens were compared. Low directivity was measured for the large element with the diverging lens while maintaining high transmit pressure. The focusing quality of 4 × 3cm matrix arrays of 16 elements without/with lenses were compared.In vitroexperiments in a water tank and through a human skull were achieved to localize and track microbubbles in tubes.Significance.ULM was achieved demonstrating the strong potential of multi-lens diffracting layer to enable microcirculation assessment over a large field of view through the bones.

Quantitative stiffness assessment of cardiac grafts using ultrasound in a porcine model: A tissue biomarker for heart transplantation.

BACKGROUND: Heart transplantation is the definitive treatment for many cardiovascular diseases. However, no ideal approach is established to evaluate heart grafts and it mostly relies on qualitative interpretation of surgeon based on the organ aspect including anatomy, color and manual palpation. In this study we propose to assess quantitatively the Shear Wave Velocity (SWV) using ultrasound as a biomarker of cardiac viability on a porcine model. METHODS: The SWV was assessed quantitatively using a clinical ultrasound elastography device (Aixplorer, Supersonics Imagine, France) linked to a robotic motorized arm (UR3, Universal Robots, Denmark) and the elastic anisotropy was obtained using a custom ultrasound research system. SWV was evaluated as function of time in two porcine heart model during 20h at controlled temperature (4°C). One control group (N = 8) with the heart removed and arrested by cold cardioplegia and immerged in a preservation solution. One ischemic group (N = 6) with the organ harvested after 30 min of in situ warm ischemia, to mimic a donation after cardiac death. Hearts graft were revived at two preservation times, at 4 h (N = 11) and 20 h (N = 10) and the parameters of the cardiac function evaluated. FINDINGS: On control hearts, SWV remained unchanged during the 4h of preservation. SWV increased significantly between 4 and 20h. For the ischemic group, SWV was found higher after 4h (3.04 +/- 0.69 vs 1.69+/-0.19 m/s, p = 0.007) and 20h (4.77+/-1.22 m/s vs 3.40+/-0.75 m/s, p = 0.034) of preservation with significant differences. A good correlation between SWV and cardiac function index was found (r2=0.88) and manual palpation score (r2=0.81). INTERPRETATION: Myocardial stiffness increase was quantified as a function of preservation time and harvesting conditions. The correlation between SWV and cardiac function index suggests that SWV could be used as a marker of graft viability. This technique may be transposed to clinical transplantation for assessing the graft viability during transplantation process. FUNDING: FRM PME20170637799, Agence Biomédecine AOR Greffe 2017, ANR-18-CE18-0015.

Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy.

BACKGROUND: Direct assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities. OBJECTIVES: The purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (<20 µm resolution) at ultrafast frame rate (>1000 images/s). METHODS: CorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel-count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3). RESULTS: CorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (<20 µm resolution). Absolute flow velocity estimates range from 10 mm/s in tiny arterioles up to more than 300 mm/s in large arteries. Fitting to a power law, the flow rate-radius relationship provides an exponent of 2.61 (r2 = 0.96; P < 0.001), which is consistent with theoretical predictions and experimental validations of scaling laws in vascular trees. A 2-fold increase of the microvascular coronary flow rate is found in response to adenosine, which is in good agreement with the overall perfusion flow rate measured in the aorta (control measurement) that increased from 8.80 ± 1.03 mL/min to 16.54 ± 2.35 mL/min (P < 0.001). The feasibility of CorULM was demonstrated in vivo for N = 3 rats. CONCLUSIONS: CorULM provides unprecedented insights into the anatomy and function of coronary arteries at the microvasculature level in beating hearts. This new technology is highly translational and has the potential to become a major tool for the clinical investigation of the coronary microcirculation.

In vivo whole brain microvascular imaging in mice using transcranial 3D Ultrasound Localization Microscopy.

BACKGROUND: Non-invasive high-resolution imaging of the cerebral vascular anatomy and function is key for the study of intracranial aneurysms, stenosis, arteriovenous malformations, and stroke, but also neurological pathologies, such as degenerative diseases. Direct visualization of the microvascular networks in the whole brain remains however challenging in vivo. METHODS: In this work, we performed 3D ultrafast ultrasound localization microscopy (ULM) using a 2D ultrasound matrix array and mapped the whole-brain microvasculature and flow at microscopic resolution in C57Bl6 mice in vivo. FINDINGS: We demonstrated that the mouse brain vasculature can be imaged directly through the intact skull at a spatial resolution of 20 µm and over the whole brain depth and at high temporal resolution (750 volumes.s-1). Individual microbubbles were tracked to estimate the flow velocities that ranged from 2 mm.s-1 in arterioles and venules up to 100 mm.s-1 in large vessels. The vascular maps were registered automatically with the Allen atlas in order to extract quantitative vascular parameters such as local flow rates and velocities in regions of interest. INTERPRETATION: We show the potential of 3D ULM to provide new insights into whole-brain vascular flow in mice models at unprecedented vascular scale for an in vivo technique. This technology is highly translational and has the potential to become a major tool for the clinical investigation of the cerebral microcirculation. FUNDING: This study was supported by the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013) / ERC Grant Agreement n° 311025 and by the Fondation Bettencourt-Schueller under the program "Physics for Medicine". We acknowledge the ART (Technological Research Accelerator) biomedical ultrasound program of INSERM.

Boosting transducer matrix sensitivity for 3D large field ultrasound localization microscopy using a multi-lens diffracting layer: a simulation study.

Mapping blood microflows of the whole brain is crucial for early diagnosis of cerebral diseases. Ultrasound localization microscopy (ULM) was recently applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale. Whole brain 3D clinical ULM remains challenging due to the transcranial energy loss which significantly reduces the imaging sensitivity. Large aperture probes with a large surface can increase both resolution and sensitivity. However, a large active surface implies thousands of acoustic elements, with limited clinical translation. In this study, we investigate via simulations a new high-sensitive 3D imaging approach based on large diverging elements, combined with an adapted beamforming with corrected delay laws, to increase sensitivity. First, pressure fields from single elements with different sizes and shapes were simulated. High directivity was measured for curved element while maintaining high transmit pressure. Matrix arrays of 256 elements with a dimension of 10 × 10 cm with small (λ/2), large (4λ), and curved elements (4λ) were compared through point spread functions analysis. A large synthetic microvessel phantom filled with 100 microbubbles per frame was imaged using the matrix arrays in a transcranial configuration. 93% of the bubbles were detected with the proposed approach demonstrating that the multi-lens diffracting layer has a strong potential to enable 3D ULM over a large field of view through the bones.

Smart Ultrasound Device for Non-Invasive Real-Time Myocardial Stiffness Quantification of the Human Heart.

Quantitative assessment of myocardial stiffness is crucial to understand and evaluate cardiac biomechanics and function. Despite the recent progresses of ultrasonic shear wave elastography, quantitative evaluation of myocardial stiffness still remains a challenge because of strong elastic anisotropy. In this paper we introduce a smart ultrasound approach for non-invasive real-time quantification of shear wave velocity (SWV) and elastic fractional anisotropy (FA) in locally transverse isotropic elastic medium such as the myocardium. The approach relies on a simultaneous multidirectional evaluation of the SWV without a prior knowledge of the fiber orientation. We demonstrated that it can quantify accurately SWV in the range of 1.5 to 6 m/s in transverse isotropic medium (FA < 0.7) using numerical simulations. Experimental validation was performed on calibrated phantoms and anisotropic ex vivo tissues. A mean absolute error of 0.22 m/s was found when compared to gold standard measurements. Finally, in vivo feasibility of myocardial anisotropic stiffness assessment was evaluated in four healthy volunteers on the antero-septo basal segment and on anterior free wall of the right ventricle (RV) in end-diastole. A mean longitudinal SWV of 1.08 ± 0.20 m/s was measured on the RV wall and 1.74 ± 0.51 m/s on the septal wall with a good intra-volunteer reproducibility (±0.18 m/s). This approach has the potential to become a clinical tool for the quantitative evaluation of myocardial stiffness and diastolic function.

4D Ultrafast Ultrasound Imaging of Naturally Occurring Shear Waves in the Human Heart.

The objectives were to develop a novel three-dimensional technology for imaging naturally occurring shear wave (SW) propagation, demonstrate feasibility on human volunteers and quantify SW velocity in different propagation directions. Imaging of natural SWs generated by valve closures has emerged to obtain a direct measurement of cardiac stiffness. Recently, natural SW velocity was assessed in two dimensions on parasternal long axis view under the assumption of a propagation direction along the septum. However, in this approach the source localization and the complex three-dimensional propagation wave path was neglected making the speed estimation unreliable. High volume rate transthoracic acquisitions of the human left ventricle (1100 volume/s) was performed with a 4D ultrafast echocardiographic scanner. Four-dimensional tissue velocity cineloops enabled visualization of aortic and mitral valve closure waves. Energy and time of flight mapping allowed propagation path visualization and source localization, respectively. Velocities were quantified along different directions. Aortic and mitral valve closure SW velocities were assessed for the three volunteers with low standard deviation. Anisotropic propagation was also found suggesting the necessity of using a three-dimensional imaging approach. Different velocities were estimated for the three directions for the aortic (3.4± 0.1 m/s, 3.5± 0.3 m/s, 5.4± 0.7 m/s) and the mitral (2.8± 0.5 m/s, 2.9± 0.3 m/s, 4.6± 0.7 m/s) valve SWs. 4D ultrafast ultrasound alleviates the limitations of 2D ultrafast ultrasound for cardiac SW imaging based on natural SW propagations and enables a comprehensive measurement of cardiac stiffness. This technique could provide stiffness mapping of the left ventricle.

Ultrafast Ultrasound Imaging in Pediatric and Adult Cardiology: Techniques, Applications, and Perspectives.

Ultrasound techniques currently used in echocardiography are limited by conventional frame rates. Ultrafast ultrasound imaging is able to capture images at frame rates up to 100 times faster compared with conventional imaging. Specific applications of this technology have been developed and tested for clinical use in pediatric and adult cardiac imaging. These include ultrafast Doppler or vector flow imaging, shear wave imaging, electromechanical wave imaging, and backscatter tensor imaging. The principles of these applications are explained in this manuscript with illustrations on how these methods could be applied in clinical practice. Ultrafast ultrasound has great clinical potential in the assessment of cardiac function, in noninvasive hemodynamic analysis, while providing novel techniques for imaging coronary perfusion and evaluating rhythm disorders.

Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is associated with arterial ruptures due to a mutant gene encoding collagen type III (Col-III). To better understand the role of Col-III, we aimed at evaluating aortic stiffness and dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice) or a qualitative Col-III defect (col3KI mice). MATERIALS AND METHODS: Abdominal aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared to their respective wild type (WT) littermates using a 15 MHz ultrafast ultrasonic transducer. A carotid catheter continuously monitored pressure changes due to phenylephrine injections. PWV1, generated at diastolic blood pressure (DBP), and PWV2, at systolic blood pressure (SBP) were recorded. Difference between PWV2 and PWV1 (Delta-PWV) normalized by the pulse pressure (PP), corresponding to the aortic stiffening over the cardiac cycle, were compared between mutant and WT mice, as well as the regression slope of PWV as a function of pressure. RESULTS: Delta-PWV/PP was lower in col3KO (p = 0.033) and col3KI mice (p < 0.001) vs. WT-mice regardless of the pressure level. The slope of PWV1 with DBP increase showed a lower arterial stiffness in mutant mice vs. controls in both models. This difference was amplified when evaluating stiffness at systolic blood pressure levels with PWV2. CONCLUSION: In both vEDS mouse models, aortic stiffening was reduced, mainly driven by a lower stiffness at systolic blood pressure. Defective Col-III may be responsible for this, as it is utilized when pressure rises. These pre-clinical data could explain vascular fragility observed in vEDS patients.

Cardiac Lesion Mapping In Vivo Using Intracardiac Myocardial Elastography.

Radio frequency (RF) ablation of the myocardium is used to treat various cardiac arrhythmias. The size, spacing, and transmurality of lesions have been shown to affect the success of the ablation procedure; however, there is currently no method to directly image the size and formation of ablation lesions in real time. Intracardiac myocardial elastography (ME) has been previously used to image the decrease in cardiac strain during systole in the ablated region as a result of the lesion formation. However, the feasibility of imaging multiple lesions and identifying the presence of gaps between lesions has not yet been investigated. In this paper, RF ablation lesions ( ) were generated in the left ventricular epicardium in three anesthetized canines. Two sets of two lesions each were created in close proximity to one another with small gaps (1.5 and 4 cm), while one set of two lesions was created directly next to each other with no gap. A clinical intracardiac echocardiography system was programmed to transmit a custom diverging beam sequence at 600 Hz and used to image the ablation site before and after the induction of ablation lesions. Cumulative strains were estimated over systole using a normalized cross-correlational displacement algorithm and a least-squares strain kernel. Afterward, lesions were excised and subjected to tetrazolium chloride staining. Results indicate that intracardiac ME was capable of imaging the reduction in systolic strain associated with the formation of an ablation lesion. Furthermore, lesion sets containing gaps were able to be distinguished from lesion sets created with no gaps. These results indicate that the end-systolic strain measured using intracardiac ME may be used to image the formation of lesions induced during an RF ablation procedure, in order to provide critical assessment of lesion viability during the interventional procedure.

Feasibility and Validation of 4-D Pulse Wave Imaging in Phantoms and In Vivo.

Pulse wave imaging (PWI) is a noninvasive technique for tracking the propagation of the pulse wave along the arterial wall. The 3-D ultrasound imaging would aid in objectively estimating the pulse wave velocity (PWV) vector. This paper aims to introduce a novel PWV estimation method along the propagation direction, validate it in phantoms, and test its feasibility in vivo. A silicone vessel phantom consisting of a stiff and a soft segment along the longitudinal axis and a silicone vessel with a plaque were constructed. A 2-D array with a center frequency of 2.5 MHz was used. Propagation was successfully visualized in 3-D in each phantom and in vivo in six healthy subjects. In three of the healthy subjects, results were compared against conventional PWI using a linear array. PWVs were estimated in the stiff (3.42 ± 0.23 m [Formula: see text]) and soft (2.41 ± 0.07 m [Formula: see text]) phantom segments. Good agreement was found with the corresponding static testing values (stiff: 3.41 m [Formula: see text] and soft: 2.48 m [Formula: see text]). PWI-derived vessel compliance values were validated with dynamic testing. Comprehensive views of pulse propagation in the plaque phantom were generated and compared against conventional PWI acquisitions. Good agreement was found in vivo between the results of 4-D PWI (4.80 ± 1.32 m [Formula: see text]) and conventional PWI (4.28±1.20 m [Formula: see text]) ( n=3 ). PWVs derived for all of the healthy subjects ( n = 6 ) were within the physiological range. Thus, the 4-D PWI was successfully validated in phantoms and used to image the pulse wave propagation in normal human subjects in vivo.

Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound Backscatter Tensor Imaging.

The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients.

3D Quasi-Static Ultrasound Elastography With Plane Wave In Vivo.

In biological tissue, an increase in elasticity is often a marker of abnormalities. Techniques such as quasi-static ultrasound elastography have been developed to assess the strain distribution in soft tissues in two dimensions using a quasi-static compression. However, as abnormalities can exhibit very heterogeneous shapes, a three dimensional approach would be necessary to accurately measure their volume and remove operator dependency. Acquisition of volumes at high rates is also critical to performing real-time imaging with a simple freehand compression. In this study, we developed for the first time a 3D quasi-static ultrasound elastography method with plane waves that estimates axial strain distribution in vivo in entire volumes at high volume rate. Acquisitions were performed with a 2D matrix array probe of 2.5 MHz frequency and 256 elements. Plane waves were emitted at a volume rate of 100 volumes/s during a continuous motorized and freehand compression. 3D B-mode volumes and 3D cumulative axial strain volumes were successfully estimated in inclusion phantoms and in ex vivo canine liver before and after a high intensity focused ultrasound ablation. We also demonstrated the in vivo feasibility of the method using freehand compression on the calf muscle of a human volunteer and were able to retrieve 3D axial strain volume at a high volume rate depicting the differences in stiffness of the two muscles which compose the calf muscle. 3D ultrasound quasi-static elastography with plane waves could become an important technique for the imaging of the elasticity in human bodies in three dimensions using simple freehand scanning.

3D Myocardial Elastography In Vivo.

Strain evaluation is of major interest in clinical cardiology as it can quantify the cardiac function. Myocardial elastography, a radio-frequency (RF)-based cross-correlation method, has been developed to evaluate the local strain distribution in the heart in vivo. However, inhomogeneities such as RF ablation lesions or infarction require a three-dimensional approach to be measured accurately. In addition, acquisitions at high volume rate are essential to evaluate the cardiac strain in three dimensions. Conventional focused transmit schemes using 2D matrix arrays, trade off sufficient volume rate for beam density or sector size to image rapid moving structure such as the heart, which lowers accuracy and precision in the strain estimation. In this study, we developed 3D myocardial elastography at high volume rates using diverging wave transmits to evaluate the local axial strain distribution in three dimensions in three open-chest canines before and after radio-frequency ablation. Acquisitions were performed with a 2.5 MHz 2D matrix array fully programmable used to emit 2000 diverging waves at 2000 volumes/s. Incremental displacements and strains enabled the visualization of rapid events during the QRS complex along with the different phases of the cardiac cycle in entire volumes. Cumulative displacement and strain volumes depict high contrast between non-ablated and ablated myocardium at the lesion location, mapping the tissue coagulation. 3D myocardial strain elastography could thus become an important technique to measure the regional strain distribution in three dimensions in humans.

3-D ultrafast Doppler imaging applied to the noninvasive mapping of blood vessels in vivo.

Ultrafast Doppler imaging was introduced as a technique to quantify blood flow in an entire 2-D field of view, expanding the field of application of ultrasound imaging to the highly sensitive anatomical and functional mapping of blood vessels. We have recently developed 3-D ultrafast ultrasound imaging, a technique that can produce thousands of ultrasound volumes per second, based on a 3-D plane and diverging wave emissions, and demonstrated its clinical feasibility in human subjects in vivo. In this study, we show that noninvasive 3-D ultrafast power Doppler, pulsed Doppler, and color Doppler imaging can be used to perform imaging of blood vessels in humans when using coherent compounding of 3-D tilted plane waves. A customized, programmable, 1024-channel ultrasound system was designed to perform 3-D ultrafast imaging. Using a 32 × 32, 3-MHz matrix phased array (Vermon, Tours, France), volumes were beamformed by coherently compounding successive tilted plane wave emissions. Doppler processing was then applied in a voxel-wise fashion. The proof of principle of 3-D ultrafast power Doppler imaging was first performed by imaging Tygon tubes of various diameters, and in vivo feasibility was demonstrated by imaging small vessels in the human thyroid. Simultaneous 3-D color and pulsed Doppler imaging using compounded emissions were also applied in the carotid artery and the jugular vein in one healthy volunteer.

4-D ultrafast shear-wave imaging.

Over the last ten years, shear wave elastography (SWE) has seen considerable development and is now routinely used in clinics to provide mechanical characterization of tissues to improve diagnosis. The most advanced technique relies on the use of an ultrafast scanner to generate and image shear waves in real time in a 2-D plane at several thousands of frames per second. We have recently introduced 3-D ultrafast ultrasound imaging to acquire with matrix probes the 3-D propagation of shear waves generated by a dedicated radiation pressure transducer in a single acquisition. In this study, we demonstrate 3-D SWE based on ultrafast volumetric imaging in a clinically applicable configuration. A 32 × 32 matrix phased array driven by a customized, programmable, 1024-channel ultrasound system was designed to perform 4-D shear-wave imaging. A matrix phased array was used to generate and control in 3-D the shear waves inside the medium using the acoustic radiation force. The same matrix array was used with 3-D coherent plane wave compounding to perform high-quality ultrafast imaging of the shear wave propagation. Volumetric ultrafast acquisitions were then beamformed in 3-D using a delay-and-sum algorithm. 3-D volumetric maps of the shear modulus were reconstructed using a time-of-flight algorithm based on local multiscale cross-correlation of shear wave profiles in the three main directions using directional filters. Results are first presented in an isotropic homogeneous and elastic breast phantom. Then, a full 3-D stiffness reconstruction of the breast was performed in vivo on healthy volunteers. This new full 3-D ultrafast ultrasound system paves the way toward real-time 3-D SWE.