Spatial Assessment of Heterogeneous Tissue Natural Frequency Using Micro-Force Optical Coherence Elastography

Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 +/- 11.0 Hz and 249.0 +/- 4.6 Hz) embedded in an agar base (355.6 +/- 0.8 Hz and 361.3 +/- 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 +/- 58.2 Hz) than muscle tissue (left side: 252.6 +/- 52.3 Hz; right side: 161.5 +/- 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.