Exploiting flow dynamics for super-resolution in contrast-enhanced ultrasound

Ultrasound localization microscopy offers new radiation-free diagnostic tools for vascular imaging deep within the tissue. Sequential localization of echoes returned from inert microbubbles with low-concentration within the bloodstream reveal the vasculature with capillary resolution. Despite its high spatial resolution, low microbubble concentrations dictate the acquisition of tens of thousands of images, over the course of several seconds to tens of seconds, to produce a single super-resolved image. %since each echo is required to be well separated from adjacent microbubbles. Such long acquisition times and stringent constraints on microbubble concentration are undesirable in many clinical scenarios. To address these restrictions, sparsity-based approaches have recently been developed. These methods reduce the total acquisition time dramatically, while maintaining good spatial resolution in settings with considerable microbubble overlap. %Yet, non of the reported methods exploit the fact that microbubbles actually flow within the bloodstream. % to improve recovery. Here, we further improve sparsity-based super-resolution ultrasound imaging by exploiting the inherent flow of microbubbles and utilize their motion kinematics. While doing so, we also provide quantitative measurements of microbubble velocities. Our method relies on simultaneous tracking and super-localization of individual microbubbles in a frame-by-frame manner, and as such, may be suitable for real-time implementation. We demonstrate the effectiveness of the proposed approach on both simulations and {\it in-vivo} contrast enhanced human prostate scans, acquired with a clinically approved scanner.Comment: 11 pages, 9 figure

Acoustical structured illumination for super-resolution ultrasound imaging.

Structured illumination microscopy is an optical method to increase the spatial resolution of wide-field fluorescence imaging beyond the diffraction limit by applying a spatially structured illumination light. Here, we extend this concept to facilitate super-resolution ultrasound imaging by manipulating the transmitted sound field to encode the high spatial frequencies into the observed image through aliasing. Post processing is applied to precisely shift the spectral components to their proper positions in k-space and effectively double the spatial resolution of the reconstructed image compared to one-way focusing. The method has broad application, including the detection of small lesions for early cancer diagnosis, improving the detection of the borders of organs and tumors, and enhancing visualization of vascular features. The method can be implemented with conventional ultrasound systems, without the need for additional components. The resulting image enhancement is demonstrated with both test objects and ex vivo rat metacarpals and phalanges

Super-resolution photoacoustic imaging via flow induced absorption fluctuations

In deep tissue photoacoustic imaging the spatial resolution is inherently limited by the acoustic wavelength. We present an approach for surpassing the acoustic diffraction limit by exploiting temporal fluctuations in the sample absorption distribution, such as those induced by flowing particles. In addition to enhanced resolution, our approach inherently provides background reduction, and can be implemented with any conventional photoacoustic imaging system. The considerable resolution increase is made possible by adapting notions from super-resolution optical fluctuations imaging (SOFI) developed for blinking fluorescent molecules, to flowing acoustic emitters. By generalizing SOFI mathematical analysis to complex valued signals, we demonstrate super-resolved photoacoustic images that are free from oscillations caused by band-limited detection. The presented technique holds potential for contrast-agent free micro-vessels imaging, as red blood cells provide a strong endogenous source of naturally fluctuating absorption

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