Diverging Polymer Acoustic Lens Design for High-Resolution Row-Column Array Ultrasound Transducers.

Spherical diverging acoustic lenses mounted on flat 2-D row-column-addressed (RCA) ultrasound transducers have shown the potential to extend the field of view (FOV) from a rectilinear to a curvilinear volume region and, thereby, enable 3-D imaging of large organs. Such lenses are usually designed for small aperture low-frequency transducers, which have limited resolution. Moreover, they are made of off-the-shelf pieces of materials, which leaves no room for optimization. We hypothesize that acoustic lenses can be designed to fit high-resolution transducers, and they can be fabricated in a fast, cost-effective, and flexible manner using a combination of 3-D printing and casting or computer numerical control (CNC) machining techniques. These lenses should increase the FOV of the array while preserving the image quality. In this work, such lenses are made in concave, convex, and compound spherical shapes and from thermoplastics and thermosetting polymers. Polymethylpentene (TPX), polystyrene (PS), polypropylene (PP), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), and room-temperature-vulcanizing (RTV) silicone diverging lenses have been fabricated and mounted on a 128 + 128 6-MHz RCA transducer. The performances of the lenses have been assessed and compared in terms of FOV, signal-to-noise ratio (SNR), bandwidth, and potential artifacts. The largest FOV (24.0.) is obtained with a 42.64-mm radius PMMA-RTV compound lens, which maintains a decent fractional bandwidth (53%) and SNR at 6 MHz (.9.1-dB amplitude drop compared with the unlensed transducer). The simple PMMA TPX, PS, PP, PDMS, and RTV lenses provide an FOV of 12.2°, 6.3°, 8.1°, 11.7°, 0.6°, and 10.4°; a fractional bandwidth of 97%, 46%, 103%, 46%, 97%, 53%, and 49%; and an amplitude drop of -5.2, -4.4, -2.8, -15.4, -6.0, and -1.8 dB, respectively. This work demonstrates that thermoplastics are suitable materials for fabricating low-attenuation convex diverging lenses for large-aperture, high-frequency 2-D transducers. This is highly desired to achieve high-resolution volumetric imaging of large organs.

Tumor spheroids accelerate persistently invading cancer cells.

Glioblastoma brain tumors form in the brain's white matter and remain one of the most lethal cancers despite intensive therapy and surgery. The complex morphology of these tumors includes infiltrative growth and gain of cell motility. Therefore, various brain-mimetic model systems have been developed to investigate invasion dynamics. Despite this, exactly how gradients of cell density, chemical signals and metabolites influence individual cells' migratory behavior remains elusive. Here we show that the gradient field induced by the spheroid-accelerates cells' invasion of the extracellular matrix. We show that cells are pushed away from the spheroid along a radial gradient, as predicted by a biased persistent random walk. Thus, our results grasp in a simple model the complex behavior of metastasizing cells. We anticipate that this well-defined and quantitative assay could be instrumental in the development of new anti-cancer strategies.

Accurate prediction of transmission through a lensed row-column addressed array.

Using a diverging lens on a row-column array (RCA) can increase the size of its volumetric image and thus significantly improve its clinical value. Here, a ray tracing method is presented to predict the position of the transmitted wave so that it can be used to make beamformed images. The usable transmitted field-of-view (FOV) is evaluated for a lensed 128 + 128 element RCA by comparing the theoretic prediction of the emitted wavefront position with three-dimensional (3D) finite element simulation of the emitted field. The FOV of the array is found to be 122° ± 2° in the direction orthogonal to the emitting elements and 28.5°-51.2°, depending on depth and element position, for the direction lying along the element. Moreover, the proposed ray tracing method is compared with a simpler thin lens model, and it is shown that the improved accuracy of the proposed method can increase the usable transmitted FOV up to 25.1°.

Single-cell tracking reveals super-spreading brain cancer cells with high persistence.

Cell migration is a fundamental characteristic of vital processes such as tissue morphogenesis, wound healing and immune cell homing to lymph nodes and inflamed or infected sites. Therefore, various brain defect diseases, chronic inflammatory diseases as well as tumor formation and metastasis are associated with aberrant or absent cell migration. We embedded multicellular brain cancer spheroids in Matrigel™ and utilized single-particle tracking to extract the paths of cells migrating away from the spheroids. We found that - in contrast to local invasion - single cell migration is independent of Matrigel™ concentration and is characterized by high directionality and persistence. Furthermore, we identified a subpopulation of super-spreading cells with >200-fold longer persistence times than the majority of cells. These results highlight yet another aspect of cell heterogeneity in tumors.