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 10x10 cm with small ( $\lambda$ /2), large (4 $\lambda$ ), and curved elements (4 $\lambda$ ) 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

Ultrafast radial modulation imaging

International audienceRadial modulation imaging improves the detection of microbubbles at high frequency by using a dual ultrasonic excitation. However, the synchronization between the imaging pulses is non-trivial because microbubbles need to be interrogated in the compression and the rarefaction phase and the time-delay difference from dispersion has to be corrected. To address these issues, we propose the use of ultrafast radial modulation imaging (uRMI). In this technique, a beat frequency between the modulation pulse (around 1 MHz) and the ultrafast pulse-repetition frequency was exploited to separate microbubbles from tissue phantom in-vitro. This led to a modulated images set in the spectral domain of the slow-time that may then be demodulated through a digital lock-in amplifier to retrieve the contrast image. Ultrafast RMI, applied on a flow phantom with microbubbles, provided a contrast-to-tissue ratio from 7.2 to 14.8 dB at 15 MHz. For flow speed lower than 0.05 mL/min, uRMI (16 dB) provided a better contrast-to-tissue ratio than other techniques: SVD spatiotemporal filter (11 dB), amplitude modulation (9 dB) or microbubbles disruption (6 dB) or. This technique may then be suitable to improve the detection of targeted microbubbles, in ultrasound molecular imaging applications, and the detection of extremely slow microbubbles moving in the finest vessels in ultrasound localization microscopy

Intervertebral disc characterization by shear wave elastography: an in-vitro preliminary study

Patient-specific numerical simulation of the spine is a useful tool both in clinic and research. While geometrical personalization of the spine is no more an issue, thanks to recent technological advances, non-invasive personalization of soft tissue’s mechanical properties remains a challenge. Ultrasound elastography is a relatively recent measurement technique allowing the evaluation of soft tissue’s elastic modulus through the measurement of shear wave speed (SWS). The aim of this study was to determine the feasibility of elastographic measurements in intervertebral disc (IVD). An in-vitro approach was chosen to test the hypothesis that SWS can be used to evaluate IVD mechanical properties and to assess measurement repeatability. Eleven oxtail IVDs were tested in compression to determine their stiffness and apparent elastic modulus at rest and at 400 N. Elastographic measurements were performed in these two conditions and compared to these mechanical parameters. The protocol was repeated six times to determine elastographic measurement repeatability. Average SWS over all samples was 5.3 ± 1.0 m/s, with a repeatability of 7 % at rest and 4.6 % at 400 N; stiffness and apparent elastic modulus were 266.3 ± 70.5 N/mm and 5.4 ± 1.1 MPa at rest, respectively, while at 400 N they were 781.0 ± 153.8 N/mm and 13.2 ± 2.4 MPa. Correlations were found between elastographic measurements and IVD mechanical properties; these preliminary results are promising for further in-vivo application.The authors are grateful to the ParisTech BiomecAM chair program on subject-specific musculoskeletal modelling for funding (with the support of Proteor, ParisTech and Yves Cotrel Foundations)

Toward Whole-Brain Minimally-Invasive Vascular Imaging

Imaging the brain vasculature can be critical for cerebral perfusion monitoring in the context of neurocritical care. Although ultrasensitive Doppler (UD) can provide good sensitivity to cerebral blood volume (CBV) in a large field of view, it remains difficult to perform through the skull. In this work, we investigate how a minimally invasive burr hole, performed for intracranial pressure (ICP) monitoring, could be used to map the entire brain vascular tree. We explored the use of a small motorized phased array probe with a non-implantable preclinical prototype in pigs. The scan duration (18 min) and coverage (62 $\pm$ 12 % of the brain) obtained allowed global CBV variations detection (relative in brain Dopplerdecrease =-3[-4-+16]% \& Dopplerincrease. = +1[-3-+15]%, n = 6 \& 5) and stroke detection (relative in core Dopplerstroke. =-25%, n = 1). This technology could one day be miniaturized to be implanted for brain perfusion monitoring in neurocritical care

4D ultrafast ultrasound flow imaging: in vivo quantification of arterial volumetric flow rate in a single heartbeat

ABSTRACT: 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

Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound

Remerciements à INRA UCEA et CR2iInternational audienceBeing able to map accurately placental blood flow in clinics could have major implications in the diagnosis and follow-up of pregnancy complications such as intrauterine growth restriction (IUGR). Moreover, the impact of such an imaging modality for a better diagnosis of placental dysfunction would require to solve the unsolved problem of discriminating the strongly intricated maternal and fetal vascular networks. However, no current imaging modality allows both to achieve sufficient sensitivity and selectivity to tell these entangled flows apart. Although ultrasound imaging would be the clinical modality of choice for such a problem, conventional Doppler echography both lacks of sensibility to detect and map the placenta microvascularization and a concept to discriminate both entangled flows. In this work, we propose to use an ultrafast Doppler imaging approach both to map with an enhanced sensitivity the small vessels of the placenta (~100 μm) and to assess the variation of the Doppler frequency simultaneously in all pixels of the image within a cardiac cycle. This approach is evaluated in vivo in the placenta of pregnant rabbits: By studying the local flow pulsatility pixel per pixel, it becomes possible to separate maternal and fetal blood in 2D from their pulsatile behavior. Significance Statement: The in vivo ability to image and discriminate maternal and fetal blood flow within the placenta is an unsolved problem which could improve the diagnosis of pregnancy complications such as intrauterine growth restriction or preeclampsia. To date, no imaging modality has both sufficient sensitivity and selectivity to discriminate these intimately entangled flows. We demonstrate that Ultrafast Doppler ultrasound method with a frame rate 100x faster than conventional imaging solves this issue. It permits the mapping of small vessels of the placenta (~100 μm) in 2D with an enhanced sensitivity. By assessing pixel-per-pixel pulsatility within single cardiac cycles, it achieves maternal and fetal blood flow discrimination

0059 : Non invasive ultrasonic chordal cutting

ObjectiveChordal cutting targeting leaflet tethering has been described to improve the efficiency of annuloplasty during ischemic mitral regurgitation surgery. Histotripsy is an ultrasound based technique for tissue fragmentation through the cavitation generated by a very intense ultrasonic pulse. In this study we investigate the feasibility of using histotripsy for chordal cutting to avoid cardiopulmonary bypass and invasive surgery in infarcted heart.MethodsExperiments were performed in vitro in explanted sheep heart (N=10) and in vivo in sheep beating heart (N=5, 40+/-4kg). In vitro, the mitral valve basal chordae was removed, fixed on a holder in a water tank. The ultrasound pulses were emitted from the therapeutic device (1- MHz focused transducer, pulses of 8μs duration, peak negative pressure of 17 MPa, repetition frequency of 100Hz) placed at a distance of 64mm. In vivo, we performed sternotomy and the device was applied on the thorax cavity which was filled out with water. We analysed MV coaptation and chordae by real time 3D echocardiography. The animals were sacrificed at the end of the procedure, for postmortem anatomical exploration of the heart.ResultsIn vitro, all the basal chordae were completely cut. The mean procedure time was 5.5 (+/-1.7) minutes. The diameter of the chordae was the main criteria affecting the duration of procedure. In the sheep, central basal chordae of anterior leaflet were completely cut. The mean procedure time was 22 (+/-9) minutes. By echography, the sectioned chordae was visible and no mitral valve prolapse was found. All the postmortem anatomical exploration of hearts confirmed the section of the basal chordea. No additional lesions were objectified.ConclusionsNoninvasive ultrasound histotripsy succeed to cut mitral valve basal chordae in vitro and in vivo in beating heart. If positive, this will open the door of completely noninvasive technique for MV repair especially in case of ischemic or functional MR

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