Functional ultrasound localization microscopy (fULM) maps brain-wide neurovascular activity at the micron scale by localizing and tracking microbubbles (MBs) within the vasculature. However, count-based MB detection limits sensitivity—especially in 3-D, where reduced imaging quality, hardware limitations, and interpolation across K³ voxels lower MB detection rates. To overcome this, we introduce backscattering ULM (B-fULM), which weights Gaussian-smoothed MB trajectories by their local backscatter amplitudes to generate functional maps with enhanced sensitivity. We derive analytical expressions linking sensitivity to the number of volumes, MB occurrence rate, detection probability, and interpolation factor, and demonstrate that incorporating backscatter amplitudes yields a higher signal-to-noise ratio than conventional count-based ULM. In vitro phantom experiments characterized the sensitivity–resolution trade-off across Gaussian kernel widths (σ), revealing that σ = 1 delivers a 27-fold sensitivity improvement with minimal loss in resolution. Applied in vivo to map whisker-evoked hemodynamic responses in the rat somatosensory barrel field (S1BF) and ventral posteromedial thalamus (VPM), B-fULM achieved spatial resolutions of 53 versus 46 μm for fULM and functional sensitivity gains of 3.8 dB in S1BF and 6.6 dB in VPM. These results establish B-fULM as a tool for high-sensitivity neurovascular imaging.
Shin et al. (Wed,) studied this question.