Tissue analysis of nephritic kidney using optical coherence elastography (OCE) Chih-Hao Liu1, Manmohan Singh1, Jiasong Li1, Chen Wu1, Raksha1, Rita Idugboe1, Yong Du1, Chandra Mohan1, Michael Twa2, and Kirill V. Larin1,3 1Department of Biomedical Engineering, University of Houston 2Department of Optometry, University of Houston 3Department of Molecular Physiology and Biophysics, Baylor College of Medicine

What is nephritis? Conventional detection: Acute Glomerulonephritis Anti-glomerular basement membrane disease -> cause inability to filter waste and extra fluid from the blood Pathology: Larger crescent formation existed in the glomeruli. Proliferation of epithelium cells increases. Conventional method Ultrasound and CT Imaging Poorer resolution (millimeter scale) and ionizing radiation[1] Poorer correlation with histology features[2] [1] K. V. Sharma, A. M. Venkatesan, D. Swerdlow, D. DaSilva, A. Beck, N. Jain, and B. J. Wood, “Image-guided adrenal and renal biopsy.,” Tech Vasc Interv Radiol, vol. 13, no. 2, pp. 100–109, Jun. 2010. [2] T. Sakai, F. H. Harris, D. J. Marsh, C. M. Bennett, and R. J. Glassock, “Extracellular fluid expansion and autoregulation in nephrotoxic serum nephritis in rats.,” Kidney Int, vol. 25, no. 4, pp. 619–628, Apr. 1984.

Optical coherence elastography OCE is a technique to measure the biomechanical properties of tissues[4-6]. Provides high spatial resolution for elasticity measurement in the order of nanometer Minimal excitation force Preserves function and structure of delicate tissues Non-invasive measurement [4]B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A Review of Optical Coherence Elastography: Fundamentals, Techniques and Prospects,” IEEE J. Select. Topics Quantum Electron., vol. 20, no. 2, pp. 272–288. [5]Liang, X., V. Crecea, and S.A. Boppart, Dynamic Optical Coherence Elastography: A Review.J Innov Opt Health Sci, 2010. 3(4): p. 221-233 [6] J. Schmitt, “OCT elastography: imaging microscopic deformation and strain of tissue,” Opt. Express, vol. 3, no. 6, pp. 199–211, 1998.

Optical coherence elastography Elastic group wave detection: Texture metric -> Fluid content (diseased feature) Induce elastic wave with focused-air pulse Reconstruct elasticity from the elastic wave velocity Elastic wave measurement is detail described in [7]: The OCE measurement is in agreement with uniaxial mechanical compression testing. (a)displacement profile of the elastic wave. (b) the measured results of gelatin. [7]S. Wang, K. Larin, J. Li et al., “A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity,” Laser Physics Letters, 10(7), 075605 (2013).  

Phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system Swept source laser: 1310 ± 75nm Aline rate: 30 kHz/per sec System resolution: Axial: 11 um Lateral: 15 um Scanning distance: 6 mm Phase sensitivity: 3 nm Air-pulse force: 11 Pa The experimental setup is detailed in [7,8] 3.3 sensitivity in air [8] R. K. Manapuram, V. G. R. Manne, and K. V. Larin, “Development of phase-stabilized swept-source OCT for the ultrasensitive quantification of microbubbles,” Laser Phys., vol. 18, no. 9, pp. 1080–1086, Sep. 2008.

Sample Preparation Mouse strain model: Protocol 129 Control x11 Nephritis x10 Protocol The capsule of all kidney samples was removed. The experiment was performed immediately after organ extraction. Each sample was immersed in saline for 4 min before OCE measurement

Elastic wave velocity calculation Elastic group velocity measurement Nephritic kidney has softer elastic Property due to: Larger content of proteinuria Higher wet/dry ratio (a) Typical OCT image of a Nephritic sample and (b) the displacement profile extracted from the red spots in (a)

Results and Discussion Elastic wave velocity vs disease state. Statistical testing was performed using a two-sample t-test In Fig. (a), it can be seen that the dispersion wave front (blue color) of the healthy kidney propagates faster than the nephritic kidney. This is due to the renal inflammation inside the cortex. The quantitative results in (b) shows that the proposed technique can efficiently detect the glomerulonephritis.

Future work Develop more elasticity metrics for a better classification Viscosity OCT structural metrics, such as optical attenuation and spatial speckle variance. Elastic wave amplitude attenuation

Reference [1] K. V. Sharma, A. M. Venkatesan, D. Swerdlow, D. DaSilva, A. Beck, N. Jain, and B. J. Wood, “Image-guided adrenal and renal biopsy.,” Tech Vasc Interv Radiol, vol. 13, no. 2, pp. 100–109, Jun. 2010. [2]T. Sakai, F. H. Harris, D. J. Marsh, C. M. Bennett, and R. J. Glassock, “Extracellular fluid expansion and autoregulation in nephrotoxic serum nephritis in rats.,” Kidney Int, vol. 25, no. 4, pp. 619–628, Apr. 1984. [3] W. Hoddick, R. B. Jeffrey, H. I. Goldberg et al., “CT and sonography of severe renal and perirenal infections,” AJR Am J Roentgenol, 140(3), 517-20 (1983). [4]B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A Review of Optical Coherence Elastography: Fundamentals, Techniques and Prospects,” [5]Liang, X., V. Crecea, and S.A. Boppart, Dynamic Optical Coherence Elastography: A Review.J Innov Opt Health Sci, 2010. 3(4): p. 221-233 [6] J. Schmitt, “OCT elastography: imaging microscopic deformation and strain of tissue,” Opt. Express, vol. 3, no. 6, pp. 199–211, 1998. [7]S. Wang, K. Larin, J. Li et al., “A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity,” Laser Physics Letters, 10(7), 075605 (2013). [8] R. K. Manapuram, V. G. R. Manne, and K. V. Larin, “Development of phase-stabilized swept-source OCT for the ultrasensitive quantification of microbubbles,” Laser Phys., vol. 18, no. 9, pp. 1080–1086, Sep. 2008. [9]C. H. Liu, M. N. Skryabina, J. Li, M. Singh, E. N. Sobol, and K. V. Larin, “Measurement of the temperature dependence of Young's modulus of cartilage by phase-sensitive optical coherence elastography,” Quantum Electron., vol. 44, no. 8, pp. 751–756, Sep. 2014. [10]J. Li, S. Wang, R. K. Manapuram, M. Singh, F. M. Menodiado, S. Aglyamov, S. Emelianov, M. D. Twa, and K. V. Larin, “Dynamic optical coherence tomography measurements of elastic wave propagation in tissue-mimicking phantoms and mouse cornea in vivo,” J. Biomed. Opt., vol. 18, no. 12, p. 121503, Dec