Overcoming the acoustic diffraction limit in photoacoustic imaging by localization of flowing absorbers

The resolution of photoacoustic imaging deep inside scattering media is limited by the acoustic diffraction limit. In this work, taking inspiration from super-resolution imaging techniques developed to beat the optical diffraction limit, we demonstrate that the localization of individual optical absorbers can provide super-resolution photoacoustic imaging well beyond the acoustic diffraction limit. As a proof-of-principle experiment, photoacoustic cross-sectional images of microfluidic channels were obtained with a 15 MHz linear CMUT array while absorbing beads were flown through the channels. The localization of individual absorbers allowed to obtain super-resolved cross-sectional image of the channels, by reconstructing both the channel width and position with an accuracy better than $\lambda/10$. Given the discrete nature of endogenous absorbers such as red blood cells, or that of exogenous particular contrast agents, localization is a promising approach to push the current resolution limits of photoacoustic imaging

Effect of Mechanical Index on Repeated Sparse Activation of Nanodroplets in Vivo

Current localization-based super-resolution ultrasound imaging requires a low concentration of flowing microbubbles to visualize microvasculature beyond the diffraction limit and acquisition is slow. Previous studies have shown that sparse activation of nanodroplets can be used for generating fast or even real-time super-resolution imaging. However, the optimal experimental conditions to activate the droplets for generating the super-resolution images are still unknown, especially the activation ultrasound amplitude or mechanical index (MI). An in vivo super-resolution image of a rabbit kidney is obtained in 1.1 seconds using AWSALM pulse sequence. The aim of this study is to investigate the effect of the activation MI on the repeated activation of nanodroplets in the rabbit kidney. It was found that the droplet activation was not observed in the rabbit kidney at a MI of 1.1. The activation of droplet started at an activation MI of 1.3. The contrast of activated droplet signals is maximized at an MI of 1.5 and decreased when the activation MI was increased above 1.5. The possible explanation might be that, at high MIs, the activated droplets were destroyed. Such understanding of the effects of activation MI could help improve droplet-base fast super-resolution imaging

3-D In Vitro Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles

Standard clinical ultrasound (US) imaging frequencies are unable to resolve microvascular structures due to the fundamental diffraction limit of US waves. Recent demonstrations of 2D super-resolution both in vitro and in vivo have demonstrated that fine vascular structures can be visualized using acoustic single bubble localization. Visualization of more complex and disordered 3D vasculature, such as that of a tumor, requires an acquisition strategy which can additionally localize bubbles in the elevational plane with high precision in order to generate super-resolution in all three dimensions. Furthermore, a particular challenge lies in the need to provide this level of visualization with minimal acquisition time. In this work, we develop a fast, coherent US imaging tool for microbubble localization in 3D using a pair of US transducers positioned at 90°. This allowed detection of point scatterer signals in 3 dimensions with average precisions equal to 1.9 µm in axial and elevational planes, and 11 µm in the lateral plane, compared to the diffraction limited point spread function full widths at half maximum of 488 µm, 1188 µm and 953 µm of the original imaging system with a single transducer. Visualization and velocity mapping of 3D in vitro structures was demonstrated far beyond the diffraction limit. The capability to measure the complete flow pattern of blood vessels associated with disease at depth would ultimately enable analysis of in vivo microvascular morphology, blood flow dynamics and occlusions resulting from disease states

Ultrasound localization microscopy to image and assess microvasculature in a rat kidney.

The recent development of ultrasound localization microscopy, where individual microbubbles (contrast agents) are detected and tracked within the vasculature, provides new opportunities for imaging the vasculature of entire organs with a spatial resolution below the diffraction limit. In stationary tissue, recent studies have demonstrated a theoretical resolution on the order of microns. In this work, single microbubbles were localized in vivo in a rat kidney using a dedicated high frame rate imaging sequence. Organ motion was tracked by assuming rigid motion (translation and rotation) and appropriate correction was applied. In contrast to previous work, coherence-based non-linear phase inversion processing was used to reject tissue echoes while maintaining echoes from very slowly moving microbubbles. Blood velocity in the small vessels was estimated by tracking microbubbles, demonstrating the potential of this technique to improve vascular characterization. Previous optical studies of microbubbles in vessels of approximately 20 microns have shown that expansion is constrained, suggesting that microbubble echoes would be difficult to detect in such regions. We therefore utilized the echoes from individual MBs as microscopic sensors of slow flow associated with such vessels and demonstrate that highly correlated, wideband echoes are detected from individual microbubbles in vessels with flow rates below 2 mm/s

Quantitative Microvessel Analysis with 3D Super-Resolution Ultrasound and Velocity Mapping

Medical image analysis is becoming increasingly accessible in the clinic. Computed tomography (CT) or magnetic resonance imaging (MRI) scans are usually post-processed to generate a 3-D visualization of the human body for surgical assistance or extract quantitative data to provide additional diagnostic information. Three dimensional super-resolution ultrasound (SR US) imaging can provide similar information at a micro-level without the high cost or ionising radiation. In this study, we implemented a high volumetric-rate 3-D SR US imaging with a 2-D spiral-shaped array and imaged an in vitro microvascular structure. From the 3-D SR US images clinically relevant parameters, such as microvascular flow rate, microvessel density and tortuosity, were extracted and compared with the ground truth