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

Abstract

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.

In vivo corneal elastography: A topical review of challenges and opportunities

“…In contrast, the dynamic OCE, including step, harmonic (sinusoid signal), spectroscopic (chirp signal), or impulse loading methods, characterize the sample response with faster motion features (such as resonation and wave propagation), and these induced motions are strain-rate- and frequency-dependent. Thus, it is essential to characterize the excitation method in the temporal and frequency domains to accurately analyze motion characteristics, such as the potential evoked frequency range [49] , [50] , [244] , [245] and the phase velocity, which is frequency dependent in a viscoelastic sample such as the cornea.…”

“…Natural frequency is an intrinsic property of a sample, which is defined as the frequency at which the sample tends to oscillate when disturbed [280] . Natural frequency oscillation in response to excitation force is intimately connected to tissue elastic properties [49] , [244] , [245] . It has been demonstrated that the natural frequency is linearly related to the square root of Young’s modulus in a simple elastic model.…”

“…For decades, ultrasound-based vibrational spectroscopy has been used to evoke and measure the resonant frequencies of samples with known size and mass [283] , [284] , but the detection resolution is still limited [285] . Phase-sensitive OCE approaches, with greater spatial and frequency resolutions, have been recently applied for vibrational or resonant response characterization by applying a variety of loading strategies, including an acoustic radiation force (ARF) ultrasound transducer [285] , piezoelectric actuator [286] or mechanical wave driver [287] , magnetomotive nanoparticle transducer [223] , [288] , [289] , air pulse [49] , [244] , [245] , and audio sound from a speaker [50] , [227] . These dynamic OCE methods have demonstrated enhanced frequency contrast in the cross-sectional as well as volumetric imaging at certain excitation frequencies [285] , [286] , [287] , [289] , and high-resolution quantification of resonant natural frequencies by providing a wide-spectrum frequency stimulation simultaneously [49] , [244] , [245] or by sweeping the driving frequencies in step [223] , [285] , [286] , [288] , [289] .…”

“…Natural frequency has been shown to be linearly correlated with the square root of Young’s modulus in a simple elastic model [223] , [244] , [285] . Spatially stimulated and measured natural frequency values can be used to recognize both the global and local features, including the locally variated mechanical properties of the heterogeneous samples [245] .…”

Corneal Surface Wave Propagation Associated with Intraocular Pressures: OCT Elastography Assessment in a Model Eye

“…A detailed description of this OCE system has been provided in our previous work [38,39]. In summary, this OCE system was built by combining a microliter air-pulse mechanical stimulation system and a 1290-nm linear-wavenumber (k) spectral domain OCT platform [40] (Figure 1a).…”