High-Frame-Rate Contrast Echocardiography using diverging waves: initial in-vitro and in-vivo evaluation

Contrast Echocardiography (CE) ultrasound with microbubble contrast agents (UCA) has significantly advanced our capability for assessment of cardiac function, including myocardium perfusion quantification. However in standard CE techniques obtained with line by line scanning, the frame rate and image quality are limited. Recent research has shown significant frame rate improvement in non-contrast cardiac imaging. In this work we present and initially evaluate, both in-vitro and in-vivo, a high frame rate (HFR) CE imaging system using diverging waves and pulse inversion sequence. An imaging frame rate of 5500 frames per second before and 250 frames per second after compounding is achieved. A destruction-replenishment sequence has also been developed. The developed HFR CE is compared with standard CE in-vitro on a phantom and then in-vivo on a sheep heart. The image signal to noise ratio, contrast between the myocardium and the chamber are evaluated. Results show up to 13.4 dB improvement in contrast for HFR CE over standard CE when compared at the same display frame-rate even when the average spatial acoustic pressure in HFR CE is 36% lower than the standard CE. It is also found that when coherent compounding is used the HFR CE image intensity can be significantly modulated by the flow motion in the chamber

3D Super-Resolution Ultrasound with Adaptive Weight-Based Beamforming

Super-resolution ultrasound (SRUS) imaging through localising and tracking sparse microbubbles has been shown to reveal microvascular structure and flow beyond the wave diffraction limit. Most SRUS studies use standard delay and sum (DAS) beamforming, where large main lobe and significant side lobes make separation and localisation of densely distributed bubbles challenging, particularly in 3D due to the typically small aperture of matrix array probes. This study aims to improve 3D SRUS by implementing a low-cost 3D coherence beamformer based on channel signal variance, as well as two other adaptive weight-based coherence beamformers: nonlinear beamforming with p-th root compression and coherence factor. The 3D coherence beamformers, together with DAS, are compared in computer simulation, on a microflow phantom, and in vivo. Simulation results demonstrate that the adaptive weight-based beamformers can significantly narrow the main lobe and suppress the side lobes for modest computational cost. Significantly improved 3D SR images of microflow phantom and a rabbit kidney are obtained through the adaptive weight-based beamformers. The proposed variance-based beamformer performs best in simulations and experiments.Comment: Ultrasound localisation microscopy (ULM), super-resolution, contrast-enhanced ultrasound, 3D beamformin

Ultrafast 3-D Super Resolution Ultrasound using Row-Column Array specific Coherence-based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, In Vivo and Clinical Study

The row-column addressed array is an emerging probe for ultrafast 3-D ultrasound imaging. It achieves this with far fewer independent electronic channels and a wider field of view than traditional 2-D matrix arrays, of the same channel count, making it a good candidate for clinical translation. However, the image quality of row-column arrays is generally poor, particularly when investigating tissue. Ultrasound localisation microscopy allows for the production of super-resolution images even when the initial image resolution is not high. Unfortunately, the row-column probe can suffer from imaging artefacts that can degrade the quality of super-resolution images as `secondary' lobes from bright microbubbles can be mistaken as microbubble events, particularly when operated using plane wave imaging. These false events move through the image in a physiologically realistic way so can be challenging to remove via tracking, leading to the production of 'false vessels'. Here, a new type of rolling window image reconstruction procedure was developed, which integrated a row-column array-specific coherence-based beamforming technique with acoustic sub-aperture processing for the purposes of reducing `secondary' lobe artefacts, noise and increasing the effective frame rate. Using an {\it{in vitro}} cross tube, it was found that the procedure reduced the percentage of `false' locations from $\sim$26\% to $\sim$15\% compared to traditional orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by $\sim$7 dB and that the effective frame rate could be increased to over 4000 fps. Subsequently, {\it{in vivo}} ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid

3D acoustic wave sparsely activated localization microscopy with phase change contrast agents

Objective The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). Materials and Methods Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C3F8 and C4F10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. Results With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 μm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. Conclusions Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration

New beamforming strategy for improved ultrasound imaging : application to biological tissues nonlinear imaging

L'échographie est aujourd'hui une technique d'imagerie de diagnostic répandue. Si l'imagerie dite ‘classique' basée sur la réponse linéaire des tissus est couramment utilisée, l'imagerie harmonique, basée sur la réponse non linéaire des tissus, est maintenant aussi utilisée en routine clinique. L'estimation du paramètre de non linéarité d'un milieu par une technique ultrasonore amène de nouvelles perspectives en termes d'imagerie et de diagnostic. Cependant, la méthode de mesure du paramètre de non linéarité est limitée par deux facteurs, la présence du speckle et la concentration de l'énergie à une profondeur donnée (la zone focale). Cette thèse a pour objectifs de répondre aux deux limitations mentionnées précédemment en proposant de nouvelles méthodes de lissage de l'image pour réduire le speckle et d'améliorer l'estimation du paramètre de non linéarité en mode écho par de nouvelles méthodes d'émission. Dans un premier temps, il a été proposé d'utiliser une méthode de filtrage spatiale basée sur des filtres orthogonaux (filtres de Thomson) lors de la formation de voie en réception pour lisser le speckle. Ce filtrage spatiale intervient après la transmission d'ondes planes sous différents angles pour améliorer la résolution spatiale et le contraste tout en accélérant la cadence d'imagerie. Dans un deuxième temps, l'estimation du paramètre de non linéarité est faite avec une méthode comparative. Le champ de pression du second harmonique d'une zone de référence est comparé avec le champ de pression d'une zone dont le paramètre de non linéarité est inconnu. Cependant, dans le cas des images échographiques, le champ de pression du second harmonique n'est pas accessible. Nous faisons l'hypothèse que la pression acoustique locale est liée à l'intensité de l'image échographique si le speckle est réduit et lissé. La transmission d'ondes planes et l'application de filtres orthogonaux permet de mieux délimiter le paramètre de non linéarité par rapport à une transmission focaliséeNowadays, ultrasound imaging is a common diagnostic tool thanks to its non-invasive behavior and relatively cheap equipment. Classic medical echographic imaging is based on the linear response of the biological tissue. However harmonic imaging, based on the harmonic frequencies generated by the nonlinear properties of the tissue, is more and more used for clinical application. The quantification of nonlinearity is based on the evaluation of the nonlinearity parameter which strongly influences the harmonics generation. The nonlinearity parameter estimation using an echographic approach would bring new modalities for imaging and diagnosis. However the echographic method for nonlinearity estimation is limited by two factors: the presence of speckles in the image and the focalization used during transmission, which concentrates the energy at one particular depth. The objectives of this thesis work are developing novel approaches to reduce the speckle noise using original smoothing techniques and improving the nonlinearity parameter estimation in echo mode using new transmission-reception strategies. Firstly, new speckle noise reduction approaches were investigated. The Thomson’s multitaper approach was proposed, consisting in using several different orthogonal apodizations during beamforming. This method was combined to a coherent plane-wave compounding transmission-reception strategy improving the spatial resolution and the contrast while improving the frame rate. In a second time, the nonlinearity parameter was estimated using a comparative method. The second-harmonic pressure field of a reference area was compared to the pressure field of an area where the nonlinearity parameter is unknown. However in echo-mode, the pressure field of the medium is unknown. It is assumed in this thesis work that the local pressure can be derived from envelope image local amplitude if the speckle noise is smoothed. The nonlinearity parameter estimation has been improved using plane-wave transmission and orthogonal apodizations compared to the use of a single focalization transmissionOggigiorno, le tecniche di imaging ad ultrasuoni sono un comune strumento di diagnosi, grazie alla loro non invasività e alla relativa economicità dei sistemi. La risposta lineare dei tessuti biologici è la base per le tecniche di imaging ecografico tradizionali. La generazione di frequenze ad armoniche superiori da parte dei tessuti può essere sfruttata per sviluppare tecniche di imaging innovative (i.e., imaging armonico), che sono sempre più utilizzate per applicazioni cliniche. Tali tecniche sono basate sul metodo di valutazione del parametro di non linearità che influenza fortemente la generazione delle armoniche all’interno dei tessuti. I metodi per la stima dei suddetti parametri sfruttano solitamente un approccio ecografico tradizionale. Di conseguenza, gli effetti legati alla focalizzazione impiegata durante la trasmissione, che concentra l’energia ad una particolare profondità, e la presenza di speckle nell’immagine finale, rendono più incerta la stima del parametro di non linearità. In questa tesi sono proposti metodi innovativi finalizzati a due scopi: ridurre, nelle immagini, il rumore dovuto a speckle, tramite l’adozione di nuove tecniche di smoothing; migliorare la stima dei parametri di non linearità, tramite l’impiego di nuove strategie di beamforming in trasmissione e ricezione. Per ridurre il rumore dovuto a speckle, è stato proposto un approccio di filtraggio spaziale basato sull’impiego dei filtri di Thomson. Tale tecnica consiste nell’impiego di numerose apodizzazioni ortogonali fra di loro in fase di beamforming. Il metodo è stato in particolare combinato con la tecnica di imaging coherent plane-wave compounding, con lo scopo di migliorare la risoluzione spaziale e il contrasto e, al contempo, incrementare il frame rate. Il parametro di non linearità è stato misurato tramite un approccio comparativo. Il campo di pressione della seconda armonica in un’area di riferimento dell’immagine è stato confrontato con quello di un’area in cui il parametro di non linearità è ignoto. In questa tesi, grazie alla riduzione del rumore speckle, è stato possibile assumere che il campo di pression

Formation de voies en émission et en réception pour l'amélioration de l'imagerie ultrasonore : application à l'imagerie non linéaire des tissus biologiques

Nowadays, ultrasound imaging is a common diagnostic tool thanks to its non-invasive behavior and relatively cheap equipment. Classic medical echographic imaging is based on the linear response of the biological tissue. However harmonic imaging, based on the harmonic frequencies generated by the nonlinear properties of the tissue, is more and more used for clinical application. The quantification of nonlinearity is based on the evaluation of the nonlinearity parameter which strongly influences the harmonics generation. The nonlinearity parameter estimation using an echographic approach would bring new modalities for imaging and diagnosis. However the echographic method for nonlinearity estimation is limited by two factors: the presence of speckles in the image and the focalization used during transmission, which concentrates the energy at one particular depth. The objectives of this thesis work are developing novel approaches to reduce the speckle noise using original smoothing techniques and improving the nonlinearity parameter estimation in echo mode using new transmission-reception strategies. Firstly, new speckle noise reduction approaches were investigated. The Thomson’s multitaper approach was proposed, consisting in using several different orthogonal apodizations during beamforming. This method was combined to a coherent plane-wave compounding transmission-reception strategy improving the spatial resolution and the contrast while improving the frame rate. In a second time, the nonlinearity parameter was estimated using a comparative method. The second-harmonic pressure field of a reference area was compared to the pressure field of an area where the nonlinearity parameter is unknown. However in echo-mode, the pressure field of the medium is unknown. It is assumed in this thesis work that the local pressure can be derived from envelope image local amplitude if the speckle noise is smoothed. The nonlinearity parameter estimation has been improved using plane-wave transmission and orthogonal apodizations compared to the use of a single focalization transmissionL'échographie est aujourd'hui une technique d'imagerie de diagnostic répandue. Si l'imagerie dite ‘classique' basée sur la réponse linéaire des tissus est couramment utilisée, l'imagerie harmonique, basée sur la réponse non linéaire des tissus, est maintenant aussi utilisée en routine clinique. L'estimation du paramètre de non linéarité d'un milieu par une technique ultrasonore amène de nouvelles perspectives en termes d'imagerie et de diagnostic. Cependant, la méthode de mesure du paramètre de non linéarité est limitée par deux facteurs, la présence du speckle et la concentration de l'énergie à une profondeur donnée (la zone focale). Cette thèse a pour objectifs de répondre aux deux limitations mentionnées précédemment en proposant de nouvelles méthodes de lissage de l'image pour réduire le speckle et d'améliorer l'estimation du paramètre de non linéarité en mode écho par de nouvelles méthodes d'émission. Dans un premier temps, il a été proposé d'utiliser une méthode de filtrage spatiale basée sur des filtres orthogonaux (filtres de Thomson) lors de la formation de voie en réception pour lisser le speckle. Ce filtrage spatiale intervient après la transmission d'ondes planes sous différents angles pour améliorer la résolution spatiale et le contraste tout en accélérant la cadence d'imagerie. Dans un deuxième temps, l'estimation du paramètre de non linéarité est faite avec une méthode comparative. Le champ de pression du second harmonique d'une zone de référence est comparé avec le champ de pression d'une zone dont le paramètre de non linéarité est inconnu. Cependant, dans le cas des images échographiques, le champ de pression du second harmonique n'est pas accessible. Nous faisons l'hypothèse que la pression acoustique locale est liée à l'intensité de l'image échographique si le speckle est réduit et lissé. La transmission d'ondes planes et l'application de filtres orthogonaux permet de mieux délimiter le paramètre de non linéarité par rapport à une transmission focaliséeOggigiorno, le tecniche di imaging ad ultrasuoni sono un comune strumento di diagnosi, grazie alla loro non invasività e alla relativa economicità dei sistemi. La risposta lineare dei tessuti biologici è la base per le tecniche di imaging ecografico tradizionali. La generazione di frequenze ad armoniche superiori da parte dei tessuti può essere sfruttata per sviluppare tecniche di imaging innovative (i.e., imaging armonico), che sono sempre più utilizzate per applicazioni cliniche. Tali tecniche sono basate sul metodo di valutazione del parametro di non linearità che influenza fortemente la generazione delle armoniche all’interno dei tessuti. I metodi per la stima dei suddetti parametri sfruttano solitamente un approccio ecografico tradizionale. Di conseguenza, gli effetti legati alla focalizzazione impiegata durante la trasmissione, che concentra l’energia ad una particolare profondità, e la presenza di speckle nell’immagine finale, rendono più incerta la stima del parametro di non linearità. In questa tesi sono proposti metodi innovativi finalizzati a due scopi: ridurre, nelle immagini, il rumore dovuto a speckle, tramite l’adozione di nuove tecniche di smoothing; migliorare la stima dei parametri di non linearità, tramite l’impiego di nuove strategie di beamforming in trasmissione e ricezione. Per ridurre il rumore dovuto a speckle, è stato proposto un approccio di filtraggio spaziale basato sull’impiego dei filtri di Thomson. Tale tecnica consiste nell’impiego di numerose apodizzazioni ortogonali fra di loro in fase di beamforming. Il metodo è stato in particolare combinato con la tecnica di imaging coherent plane-wave compounding, con lo scopo di migliorare la risoluzione spaziale e il contrasto e, al contempo, incrementare il frame rate. Il parametro di non linearità è stato misurato tramite un approccio comparativo. Il campo di pressione della seconda armonica in un’area di riferimento dell’immagine è stato confrontato con quello di un’area in cui il parametro di non linearità è ignoto. In questa tesi, grazie alla riduzione del rumore speckle, è stato possibile assumere che il campo di pression