Heartbeat Optical Coherence Elastography: A Method for Passive Biomechanical Assessment of the Cornea



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In this dissertation, the biomechanical properties of the cornea are explored using a novel, completely passive, biomechanical analysis technique termed heartbeat optical coherence elastography (Hb-OCE). This technology enables mechanical characterization of the cornea with applications in disease detection, staging, and therapeutic monitoring. This dissertation explores the development and evolution of the Hb-OCE technique and is divided accordingly. In the first chapter, the need for biomechanical analysis in ocular health and diagnostics and the tools available to perform that task are discussed. The second chapter describes the development of the Hb-OCE technique. Hb-OCE was initially demonstrated in a proof-of-concept ex vivo investigation. The mechanical properties of the cornea were measured in response to a simulated ocular pulse. The capabilities of the technique were initially demonstrated, including its ability to identify spatial mechanical contrast in a heterogenous sample. In the next chapter, the Hb-OCE technique is compared to better established optical elastography techniques to investigate the effects of collagen XII deficiency on the biomechanical properties of the murine cornea ex vivo. Hb-OCE was successfully used to distinguish collagen XII deficient tissue from the wild-type, and the ability of Hb-OCE to detect tissue elastic nonlinearity was demonstrated. In the fourth chapter, Hb-OCE is demonstrated in vivo, successfully illustrating that not only can the technique detect mechanical contrast in vivo, but corneal stiffness can be measured using only the heartbeat-induced ocular pulse as a source of displacement. The fifth chapter discusses how Hb-OCE was compared to a similar quasi-static but active elastography technique known as compression elastography. Furthermore, stiffness mapping using Hb-OCE was demonstrated for the first time. Finally, this dissertation concludes with closing thoughts on areas of technical improvements and future applications.



Cornea, Biomechanics, Elastography, Optical coherence tomography, Optical coherence elastography


Portions of this document appear in: Nair, A., Singh, M., Aglyamov, S.R. and Larin, K.V., 2020. Heartbeat OCE: corneal biomechanical response to simulated heartbeat pulsation measured by optical coherence elastography. Journal of Biomedical Optics, 25(5), p.055001; and in: Nair, A., Singh, M., Aglyamov, S. and Larin, K.V., 2021. Heartbeat optical coherence elastography: corneal biomechanics in vivo. Journal of Biomedical Optics, 26(2), p.020502; and in: Nair, A., Singh, M., Aglyamov, S.R. and Larin, K.V., 2022. Multimodal Heartbeat and Compression Optical Coherence Elastography for Mapping Corneal Biomechanics. Frontiers in Medicine, 9.