Precise scatterer localization for ultrasound contrast imaging

This thesis is concerned with developing algorithms for the precise localization of ultrasound point scatterers with an eye to super-resolution ultrasound contrast imaging. In medical ultrasound, the conventional resolution is limited by diffraction and, in contrast to other sensing fields, point source imaging has not been extensively investigated. Here, two independent methods were proposed aiming to increase the lateral and the axial resolution respectively, by improving the localization accuracy of a single scatterer. The methods were examined with simulated and experimental data by using standard transmission protocols. Where a technique is applicable to imaging of more complicated structures than point sources, this was also examined. Further, a preliminary study was included with algorithm application to microbubbles that are currently used in contrast enhanced ultrasound. It was demonstrated that it is feasible to translate to ultrasonics, adaptive processes or techniques from optical imaging/astronomy. This way, it was possible to overcome the diffraction limit and achieve sub-wavelength localization. The accuracy gains are subject to many parameters but may reach up to two orders of magnitude, and are based exclusively on array signal processing. The latter is an important advantage since current attempts for super-resolution ultrasound are image-based which is generally undesired

Focusing Light Inside Scattering Media with Optical Phase Conjugation

In scattering media such as biological tissue, the heterogeneous refractive index distribution causes light to scatter, which makes the media look opaque and prevents us from focusing light beyond ~1 mm deep inside the media to achieve optical imaging and manipulation. Hence, the ability to focus light deep inside scattering media is highly desired, and it could revolutionize biophotonics by enabling deep-tissue non-invasive high-resolution optical microscopy, optical tweezing, optogenetics, micro-surgery, and phototherapy. To break the optical diffusion limit and focus light deep inside scattering media, optical phase conjugation based wavefront shaping techniques, such as time-reversed ultrasonically encoded (TRUE) optical focusing, are being actively developed. In this dissertation, I will describe our efforts to improve the performance (speed, focusing quality and focusing depth) of optical phase conjugation for future in vivo applications. Remarkably, we have focused light through tissue-mimicking phantoms up to 96 mm thick, and through ex vivo chicken breast tissue up to 25 mm thick

Dual-mode photoacoustic and ultrasound imaging system based on a Fabry-Pérot scanner

The planar Fabry-Pérot (FP) scanner is an ultrasound detector that simultaneously provides high sensitivity, a high density of small (sub-100 μm) acoustic elements, and a broad bandwidth (> 30 MHz). These features enable the FP scanner to acquire high-resolution 3D in vivo photoacoustic images of biological tissues up to depths of approximately 10 mm. The aim was to add complementary morphological ultrasound contrast to photoacoustic images to extend their clinical applicability. This was achieved by developing a dual-mode photoacoustic and ultrasound imaging system based on the FP scanner, which was modified to transmit optically generated ultrasound. The FP sensor head was coated with an optically absorbing polydimethylsiloxane(PDMS) composite layer, which was excited with nanosecond laser pulses to generate broadband planar ultrasound waves for pulse-echo imaging. First, an all-optical ultrasound system was developed using a highly absorbing carbon nanotube-PDMS composite coating. The system was characterised with a series of experiments, and its imaging performance was tested on tissue mimicking phantoms and ex vivo tissue samples. Second, the effect of the frequency content of the detected signals and the effect of spatial aliasing on the image quality were investigated in simulation. A broadband system was found to reduce the effect of spatial undersampling of high frequencies which results in a reduction of contrast due to the formation of grating lobe artefacts. Third, to improve the image quality, frequency and angle compounding were explored in simulations and experimentally. Coherent and incoherent compounding were considered, as well as the effect of the filter bandwidth on frequency compounded images, and the influence of the number and spread of angles used in angle compounded images. Finally, a dual- mode photoacoustic and ultrasound imaging system was demonstrated with a gold nanoparticle-PDMS composite which enabled wavelength-selective absorption of light. The system was shown to obtain high-resolution 3D dual-mode images providing complementary contrast from optically absorbing and acoustically scattering structures

Fast 3D super-resolution ultrasound with adaptive weight-based beamforming

Objective: 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 high side lobes and broad main lobes make isolation and localisation of densely distributed bubbles challenging, particularly in 3D due to the typically small aperture of matrix array probes. Method: This study aimed to improve 3D SRUS by implementing a new fast 3D coherence beamformer based on channel signal variance. Two additional fast coherence beamformers, that have been implemented in 2D were implemented in 3D for the first time as comparison: a nonlinear beamformer with p-th root compression and a coherence factor beamformer. The 3D coherence beamformers, together with DAS, were compared in computer simulation, on a microflow phantom and in vivo. Results: Simulation results demonstrated that all three adaptive weight-based beamformers can narrow the main lobe suppress the side lobes, while maintaining the weaker scatter signals. Improved 3D SRUS images of microflow phantom and a rabbit kidney within a 3-second acquisition were obtained using the adaptive weight-based beamformers, when compared with DAS. Conclusion: The adaptive weight-based 3D beamformers can improve the SRUS and the proposed variance-based beamformer performs best in simulations and experiments. Significance: Fast 3D SRUS would significantly enhance the potential utility of this emerging imaging modality in a broad range of biomedical applications