Development of Simultaneous Optical Imaging and Super-Resolution Ultrasound to Improve Microbubble Localization Accuracy

Acoustic super-resolution (SR) has the potential to visualize microvasculature by localizing individual microbubble (MB) signals. Currently, all detected signals are processed and localized identically. However, the MB point spread function (PSF) is not independent of its surroundings. Despite accuracy on the order of microns being required, it is currently not possible to quantify error that may be introduced due to variation in the MB responses. This work combines high frame rate plane wave ultrasound acquisition with a coincident optical microscope visualizing the SR imaging of a 200 μm cellulose tube. An adjustable aperture has been introduced into the optical microscope to extend the optical depth of field over the phantom. The results showed that the introduction of the aperture enabled modest extension of the depth of field over 50 μm about the optical focus. Modelling and experimental verification found that, at a flow rate of 15 μl/min, MBs could only be detected over the top 70 μm of the tube phantom - further reducing the required depth of field. The simultaneous optical and acoustic data suggested that many fewer MBs acoustically contribute to the SR image than can be observed in the optical FOV. Investigations incorporating a ground truth, like this one, will allow sources of error to be identified, quantified and limited.