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We report the potentials of nanometer-sized contrast agents which are called gas vesicles (GVs) for super-resolution ultrasound (SRUS) imaging to diagnose of vasculature deep inside tissue. Thus, we developed the GVs and ultrasound localization microscopy (ULM) based on singular value decomposition and 2D cross-correlation techniques. Furthermore, the SRUS imaging of the vessel-mimicking phantom with the GVs was performed. These results demonstrate that GVs could have potentials as novel contrast agents at nanoscale for implementing the SRUS imaging, thus indicating that ULM with GVs would be used for better visualization of micro-vasculature in vivo. 

The live visualization with fast kinetics of the interaction between cells has been long term challenges because of the lack of efficient stimulation methods. We propose an approach to achieve single cell resolution stimulation and FRET-base calcium live cell imaging to visualize fast kinetics of calcium transport between physically connect neighboring cells. Chemical stimulation stimulates cells within a dish at the same time and is not suitable for the study of cell-cell interaction. We replaced chemical stimulation with ultrasound-based mechanical stimulation approach to provide precise spatiotemporal resolution. To achieve this, we integrated 3D translation stages and epi-fluorescence microscope and a developed 150 MHz high frequency ultrasound with f number of 1 and aperture size of 1 mm. The 150 MHz transducer can focus within 10 micrometers in diameter and directly stimulate cells by disturbing cell plasma membranes without microbubbles. High frequency stimulation was used to introduce calcium ions into cytoplasm of cells. Results demonstrate calcium transport between cells, visualized by FRET calcium biosensor after only one cell was stimulated by the developed high frequency ultrasonic transducer.