Optical time-harmonic elastography for multiscale stiffness mapping across the phylogenetic tree

Rapid mapping of the mechanical properties of soft biological tissues from light microscopy to macroscopic imaging could transform fundamental biophysical research by providing clinical biomarkers to complement in vivo elastography. We here introduce superfast optical time-harmonic elastography (OTHE) to remotely encode surface and subsurface shear wave fields for generating maps of tissue stiffness with unprecedented detail resolution. OTHE rigorously exploits the space-time propagation characteristics of time-harmonic waves to address current limitations of biomechanical imaging and elastography. Key solutions are presented for stimulation, encoding, and stiffness reconstruction of time-harmonic, multifrequency shear waves, all tuned to provide consistent stiffness values across resolutions from microns to millimeters. OTHE's versatility is demonstrated in Bacillus subtilis biofilms, zebrafish embryos, adult zebrafish, and human skeletal muscle, reflecting the diversity of the phylogenetic tree from a mechanics perspective. By zooming in on stiffness details from coarse to finer scales, OTHE advances developmental biology and offers a way to perform biomechanics-based tissue histology that consistently matches in vivo time-harmonic elastography in patients.