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

Improved localization accuracy in stochastic super-resolution fluorescence microscopy by K-factor image deshadowing

pre-printLocalization of a single fluorescent particle with sub-diffraction-limit accuracy is a key merit in localization microscopy. Existing methods such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) achieve localization accuracies of single emitters that can reach an order of magnitude lower than the conventional resolving capabilities of optical microscopy. However, these techniques require a sparse distribution of simultaneously activated fluorophores in the field of view, resulting in larger time needed for the construction of the full image. In this paper we present the use of a nonlinear image decomposition algorithm termed K-factor, which reduces an image into a nonlinear set of contrast-ordered decompositions whose joint product reassembles the original image. The K-factor technique, when implemented on raw data prior to localization, can improve the localization accuracy of standard existing methods, and also enable the localization of overlapping particles, allowing the use of increased fluorophore activation density, and thereby increased data collection speed. Numerical simulations of fluorescence data with random probe positions, and especially at high densities of activated fluorophores, demonstrate an improvement of up to 85% in the localization precision compared to single fitting techniques. Implementing the proposed concept on experimental data of cellular structures yielded a 37% improvement in resolution for the same super-resolution image acquisition time, and a decrease of 42% in the collection time of super-resolution data with the same resolution

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

Imaging beyond ultrasonically-impenetrable objects

Abstract Ultrasound images are severely degraded by the presence of obstacles such as bones and air gaps along the beam path. This paper describes a method for imaging structures that are distal to obstacles that are otherwise impenetrable to ultrasound. The method uses an optically-inspired holographic algorithm to beam-shape the emitted ultrasound field in order to bypass the obstacle and place the beam focus beyond the obstruction. The resulting performance depends on the transducer aperture, the size and position of the obstacle, and the position of the target. Improvement compared to standard ultrasound imaging is significant for obstacles for which the width is larger than one fourth of the transducer aperture and the depth is within a few centimeters of the transducer. For such cases, the improvement in focal intensity at the location of the target reaches 30-fold, and the improvement in peak-to-side-lobe ratio reaches 3-fold. The method can be implemented in conventional ultrasound systems, and the entire process can be performed in real time. This method has applications in the fields of cancer detection, abdominal imaging, imaging of vertebral structure and ultrasound tomography. Here, its effectiveness is demonstrated using wire targets, tissue mimicking phantoms and an ex vivo biological sample

Visualization 1: Superresolved nanoscopy using Brownian motion of fluorescently labeled gold nanoparticles

Construction of the super resolution image Originally published in Applied Optics on 10 February 2017 (ao-56-5-1365