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.

Highlights

  • Soft tissue biomechanics are highly dependent upon tissue structure, materials, and composition, and they often change alongside pathological changes, such as swelling, inflammation, and tumor growth (Dupps and Wilson, 2006; Sigrist et al, 2017; Chong and Dupps, 2021)

  • We spatially characterized the dominant natural frequency distributions for heterogeneous tissues and samples using the low-force Optical coherence elastography (OCE) method, and we demonstrated that the natural frequency property is a global factor determined by mass, stiffness, and thickness (Crecea et al, 2009; Qi et al, 2013; Lan et al, 2020b; Lan et al, 2021a), but it is affected by local features, such as regional variations in shape, stiffness, and material

  • As the magnitude of each frequency component varied across the sample, the dominant natural frequency fn for a specific measurement position could represent the dominant feature in that region

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Summary

Introduction

Soft tissue biomechanics (e.g., stiffness, elasticity, and viscosity) are highly dependent upon tissue structure, materials, and composition, and they often change alongside pathological changes, such as swelling, inflammation, and tumor growth (Dupps and Wilson, 2006; Sigrist et al, 2017; Chong and Dupps, 2021) Elastic imaging methods, such as ultrasound elastography (Ophir et al, 1991) and magnetic resonance imaging (MRI) elastography (Muthupillai et al, 1995), have been developed to identify lesion areas based on mechanical contrast (e.g., strain map or wave propagations). Large-amplitude (e.g., 70–300 kPa) stimulation force can result in global corneal deformation, ocular motion, aqueous fluid displacement, as well as globe retraction and rotation (Boszczyk et al, 2017; Jiménez-villar et al, 2019) These factors confound the measurements of these ocular biomechanics measurement methods and limit the capability for detecting regional variations in corneal stiffness (Singh et al, 2017). To date, measuring corneal biomechanical properties in vivo remains challenging, and there is no gold standard for assessing corneal biomechanics spatially and locally

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