ARF-OCE for mapping mechanical properties of ocular and vascular tissues

Elastography is an imaging modality for clinical diagnosis based on the tissue stiffness. Benefiting from the high resolution, three-dimensional, and noninvasive nature of optical coherence tomography (OCT), optical coherence elastography (OCE) has the ability to determine elastic properties with a resolution of ~10 μm in 3D. Typical OCE imaging includes excitation for inducing mechanical vibrations, measurement of the sample response using OCT, and estimation of elastic parameters. Acoustic radiation force (ARF) generated by an ultrasonic transducer can noninvasively excite internal tissues without contact; thus, ARF-OCE is suitable for measuring the mechanical properties in deeper tissues. For assessment of the elastic properties of tissues using ARF-OCE, the shear wave velocity, resonant frequency, and vibrational displacement can be measured. Shear wave velocity measurements can be conveniently used for quantitative calculation of the elastic modulus.1-3 The resonant frequency of a tissue has a squared relationship with the Young\u27s modulus, and thus can quantify the elasticity.4 Vibrational displacement can be compared directly when the same pressure is applied to different samples.5 Several diseases are accompanied by and result in the changes in composition and local geometry of tissues. Keratoconus, which causes vision distortions and blurriness, will change the geometry of the cornea. The development of presbyopia is generally caused by the loss of elasticity in the lens. The composition and biomechanical properties of vessels will usually be altered when atherosclerosis occurs. The ARF-OCE technology provides a new opportunity for the early diagnosis of ocular and vascular diseases. Based on the shear wave measurements, our system can be used to quantify the elastic modulus of the cornea and the crystalline lens. By comparing the vibrational displacement, we have detected the differences between normal and cross-linked cornea.6 Recently we developed a miniature probe for mapping the mechanical properties of vascular lesions using ARF-OCE. It has the ability to detect the a vulnerable plaque due to its higher stiffness.7 Because of the noninvasive nature, ARF-OCE has the potential to perform in vivo imaging of deep tissues for the early diagnosis of ocular and vascular diseases. 1. Zhu, J., Qu, Y., Ma, T., Li, R., Du, Y., Huang, S., Shung, K.K., Zhou, Q. and Chen, Z., 2015. Imaging and characterizing shear wave and shear modulus under orthogonal acoustic radiation force excitation using OCT Doppler variance method. Optics letters, 40(9): 2099-2102. 2. Zhu, J., Qi, L., Miao, Y., Ma, T., Dai, C., Qu, Y., He, Y., Gao, Y., Zhou, Q. and Chen, Z., 2016. 3D mapping of elastic modulus using shear wave optical micro-elastography. Scientific reports, 6: 35499. 3. Xu, X., Zhu, J. and Chen, Z., 2016. Dynamic and quantitative assessment of blood coagulation using optical coherence elastography. Scientific reports, 6: 24294. 4. Qi, W., Li, R., Ma, T., Li, J., Kirk Shung, K., Zhou, Q. and Chen, Z., 2013. Resonant acoustic radiation force optical coherence elastography. Applied physics letters, 103(10): 103704. 5. Qi, W., Li, R., Ma, T., Kirk Shung, K., Zhou, Q. and Chen, Z., 2014. Confocal acoustic radiation force optical coherence elastography using a ring ultrasonic transducer. Applied physics letters, 104(12): 123702. 6. Qu, Y., Ma, T., He, Y., Zhu, J., Dai, C., Yu, M., Huang, S., Lu, F., Shung, K.K., Zhou, Q. and Chen, Z., 2016. Acoustic radiation force optical coherence elastography of corneal tissue. IEEE Journal of Selected Topics in Quantum Electronics, 22(3): 288-294. Qu, Y., Ma, T., He, Y., Yu, M., Zhu, J., Miao, Y., Dai, C., Patel, P., Shung, K.K., Zhou, Q. and Chen, Z., 2017. Miniature probe for mapping mechanical properties of vascular lesions using acoustic radiation force optical coherence elastography. Scientific Reports, 7: 473

Development of acoustic radiation force optical coherence elastography system for in vivo mapping of biological tissues

Mechanical elasticity often serves as a major indicator for pathological changes in ocular as well as intravascular diseases. For example, age-related macular degeneration is an ocular disease that occurs in the posterior eye, where central vision gets damaged due to drusen formation and neovascularization. The mechanical elasticity of the tissue is often altered during the onset of disease before structural changes are detectable with existing technologies. It is necessary to detect these changes early and provide timely treatment due to either the irreversible nature of the disease progression or the fatal consequences associated with late diagnosis. This thesis focuses on the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system to map the mechanical elasticity of tissues, and the translation of this laboratory technology to in vivo animal studies. This technique uses ultrasonic excitation to apply a force onto the tissue and optical coherence elastography to detect the spatial and frequency responses of the tissue, which combines to quantify the elasticity and provide an elasticity map. The resonance frequency method is validated and used to measure the bulk modulus of the tissue while a Voigt spring model calculates the individual layer elasticity. We first test the feasibility of the system using tissue-mimicking phantoms. Then we perform tissue imaging on the ex vivo anterior and posterior eye, where we are able to provide quantified elasticity maps of the rabbit cornea and porcine retina The system is then translated to in vivo imaging, for which quantified elasticity mapping of the rabbit retinal layers can be obtained. In addition, we have also fabricated an ARF-OCE catheter with a diameter of 3.5 mm, which was validated using phantom studies, and intravascular imaging was performed on a human cadaver artery. This study is a major stepping stone to the translation of the ARF-OCE technology in measuring the mechanical properties of tissues in clinical settings. Future studies using this technology include monitoring the retinal elasticity during and after electrode stimulation treatment and also intravascular elasticity imaging to diagnose atherosclerosis

Characterization of spectral-domain OCT with autocorrelation interference response for axial resolution performance.

We present a class of novel system characterization methods for spectral-domain optical coherence tomography (SD-OCT) particularly on getting optimized axial resolution performance. Our schemes uniquely utilize the autocorrelation interference response, also known as the self-interference product, which is generated by the optical fields from the imaging sample in automatic interferences. In our methods, an autocorrelation-inducing calibration sample was prepared which was made by sandwiching glass plates. OCT images of the calibration sample were captured by an SD-OCT system under testing. And the image data were processed to find various system characteristics based on the unique properties of autocorrelation interferograms, free of dispersion- and polarization-involved modulations. First, we could analyze the sampling characteristic of the SD-OCT's spectrometer for spectral calibration that enables accurate linear-k resampling of detected spectral fringes. Second, we could obtain the systematic polarization properties for quantifying their impact on the achieved axial resolutions. We found that our methods based on the autocorrelation response provide an easy way of self-characterization and self-validation that is useful in optimizing and maintaining axial resolution performances. It was found very attractive that a variety of system characteristics can be obtained in a single-shot measurement without any increased system complexity

Characterization of oviduct ciliary beat frequency using real time phase resolved Doppler spectrally encoded interferometric microscopy.

Ciliary activity, characterized by the coordinated beating of ciliary cells, generates the primary driving force for oviduct tubal transport, which is an essential physiological process for successful pregnancies. Malfunction of the cilium in the fallopian tube, or oviduct, may increase the risk of infertility and tubal pregnancy that can result in maternal death. While many ex-vivo studies have been carried out using bright field microscopy, this technique is not feasible for the in-vivo investigation of oviduct ciliary beating frequency (CBF). Optical coherence tomography (OCT) has been able to provide in-vivo CBF imaging in a mouse model, but its resolution may be insufficient to resolve the spatial and temporal features of the cilium. Our group has recently developed the phase resolved Doppler (PRD) OCT method to visualize ciliary strokes at ultra-high displacement sensitivity. However, the cross-sectional field of view (FOV) may not be ideal for visualizing the surface dynamics of ciliated tissue. In this study, we report on the development of phase resolved Doppler spectrally encoded interferometric microscopy (PRD-SEIM) to visualize the oviduct ciliary activity within an en face FOV. This novel real time imaging system offers micrometer spatial resolution, sub-nanometer displacement sensitivity, and the potential for in-vivo endoscopic adaptation. The feasibility of the approach has been validated through ex-vivo experiments where the porcine oviduct CBF has been measured across different temperature conditions and the application of a drug. CBF ranging from 8 to 12 Hz have been observed at different temperatures, while administration of lidocaine decreased the CBF and deactivated the motile cilia. This study will serve as a stepping stone to in-vivo oviduct ciliary endoscopy and future clinical translations

Spatially mapping of tracheal ciliary beat frequency using real time phase resolved Doppler spectrally encoded interferometric microscopy (Conference Presentation)

Ciliary motion in the upper airway is the primary mechanism by which the body transports foreign particulate out of the respiratory system in order to maintain proper respiratory function. The ciliary beating frequency (CBF) is often disrupted with the onset of disease as well as other conditions, such as changes in temperature or in response to drug administration. Current imaging of ciliary motion relies on microscopy and high speed cameras, which cannot be easily adapted to in-vivo imaging. M-mode optical coherence tomography (OCT) imaging is capable of visualization of ciliary activity, and phase-resolved Doppler (PRD) algorithm can be integrated to measure the ciliary beating direction and amplitude with nanometer sensitivity. However, since ciliary activity naturally happens on the tissue surface, enface imaging modalities should be more suitable than cross-sectional ones such as OCT. We report on the development of a spectrally encoded interferometric microscopy (SEIM) system using a phase-resolved Doppler (PRD) algorithm to measure and map the ciliary beating frequency within an en face region. This novel high speed, high resolution system allows for visualization of both temporal and spatial ciliary motion patterns with nanometer sensitivity. Rabbit tracheal CBF ranging from 9 to 13 Hz have been observed under different temperature conditions, and the effects of using lidocaine and albuterol have also been measured. This study is the stepping stone to in-vivo studies and the translation of imaging spatial CBF in clinics