Tissue classification 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: Structural information Ultrasound and CT Imaging Poorer resolution (millimeter scale) and ionizing radiation[1] Poorer correlation with histology features[2] Pathology: Extracellular fluid distributed in the diseased cortex area Nephritic kidney images of (a)CT and (b)sonography [3] OCT image of (a) normal and (b) nephritic kidneys [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).

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[9,10]. (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 Central wavelength:1310nm Bandwidth:≈150nm Axial resolution:≈11μm in air Output power:≈29mW Phase stability:≈3nm in air Pressure of air-pulse on kidney surface:≈20Pa The experimental setup is detailed in [7,8] 3.3 sensitivity in air Schematic of PhS-SSOCE system [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 B6 129 Control x5 Nephritis x10 129 Control x3 Nephritis x6 (critical state) 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 Procedure: Unwrap the displacement profile Remove the low frequency noise Cross correlate normalized displacement profiles to obtain elastic wave propagation delay Average velocity achieve from time delay and elastic wave propagation distance to calculate velocity for each depth Use median value of depths (a) Typical OCT image of a healthy sample and (b) the displacement profile extracted from the white line in (a)

Results and Discussion Elastic wave velocity vs disease state. Statistical testing was performed using a two-sample Student’s t-test Based on the statistically significant difference of the elastic wave velocities, the diseased kidneys had a softer texture than the healthy kidneys because a higher elastic wave velocity is correlated to a stiffer tissue. The increased stiffness is due to the existence of more extracellular fluid in the cortex region of the diseased kidneys.

Result and Discussion Critical state The elastic wave velocities of (a) the healthy versus the diseased kidneys, and (b) the B6 diseased versus 129 diseased sample. The healthy kidneys show a statically significant difference than the diseased group. In addition, in (b) the critical state of nephritic disease (129) is softer due to even more extracellular fluid distributed in the cortex region. The results show that OCE is a promising method for detecting nephritis.

Future work Develop more elasticity metrics for a better classification Viscosity Young’s modulus Lamb frequency equation 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