Chen Wu 1, Zhaolong Han 1, Shang Wang 1,5, Jiasong Li 1, Manmohan Singh 1, Chih-hao Liu 1, Salavat Aglyamov 2, Stanislav Emelianov 2, Fabrice Manns 3,4, and Kirill V. Larin 1,5,+ 1 Department of Biomedical Engineering, University of Houston, 3605 Cullen Boulevard, Houston, Texas 77204, USA 2 Department of Biomedical Engineering, University of Texas at Austin, 107 W Dean Keeton Street, Austin, Texas 78712, USA 3 Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10 th Avenue, Miami, Florida 33136, USA 4 Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, 1251 Memorial Drive, Coral Gables, Florida 33146, USA 5 Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77584, USA

 Motivation  Experimental Setup  Materials and Samples  Result and Discussion  Summary  Acknowledgements

 The age-related changes in viscoelastic properties of the crystalline lens play an important role in the development of presbyopia, which is the progressive, age-related loss of accommodation of the eye.  The increase in lens stiffness is generally believed to be responsible for the progressive loss of the ability of the lens to change shape leading to presbyopia.  The location of the crystalline lens inside the eye makes it challenging to measure its mechanical properties in vivo or in situ.

Elastography is an emerging technique that can map the local mechanical properties of tissues Ultrasound elastography (USE) magnetic resonance elastography (MRE) Relative low spatial resolution pose a limitation Brillouin microscopy is a new technique to study biomechanical property of lens. Uncertainty on correlation of brillouin shift to Young’s modulus In this study, we combine ultrasound excitation with Optical coherence elastography (OCE) for investigation of biomechanical properties of lens. spatial imaging resolution, faster acquisition speed, and greater displacement sensitivity

 Spectral domain OCT Laser Source Central wavelength ~840nm bandwidth~49nm)  Ultrasound system Ultrasound transducer (Model ISO305HP) Frequency~3.7MHz Focal length~19mm Function Generator Power Amplifier Gain~40dB  Adjustable transducer holder

 TTL trigger signal from the DAQ.  The TTL signal trigger the sinusoidal wave for ultrasound excitation and camera recording simultaneously.  The sinusoidal wave is set to be 3.7MHz and the excitation force can be changed by adjusting the voltage.

o Three young rabbit eyes ~ around 2-3 months old. o Four mature rabbit eyes ~ over 6 months old. o All the samples were conducted with OCE test, and then the lenses were dissected out and followed by mechanical compression tests.

 The phase profile during ultrasound excitation, the phase value and physical displacement is converted by  Displacement = wavelength*phase/(4*pi)  The displacement for young lenses ~ 3.3±0.1 µm & mature lenses ~ 1.6±0.4 µm  SD for mature ones is much larger.

The simplified kinematical differential equation can be used to describe the lens’s relaxation process: where m is the equivalent mass, c is the viscosity coefficient and k is the equivalent spring stiffness; For simplifying and understanding the basic characteristics of the equation, two parameters, ξ and ω, are introduced where is the damping ratio and is the natural frequency of the dynamic system: The analytical solution of equation above is: is the natural frequency of the dynamic system

Natural frequency values of the young and the mature lenses are 0.8±0.2 kHz and 2.2±0.5 kHz

Figure a shows typical stress-strain curves for young and mature sample. Figure b demonstrates the Young’s moduli calculated from all samples. Young’s modulus of Young lens ~ 8.2±1.1 kPa. Young’s modulus of mature lens ~ 12.6±1.2 kPa.

1) Developed a co-focused ultrasound and OCE system to study the biomechanical property of the rabbit lens; 2) The parameters of maximal displacement, natural frequency can be used for assessment; 3) Stiffness of the rabbit crystalline lens increases with age; 4) Prospective future work would be to correlate the relaxation process with a quantitative evaluation of the lens elasticity and to perform depth-resolved OCE measurements to map elasticity gradient as a function of depth.

This work was supported by the National Institutes of Health under grants R01EY and R01EY