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Evaluating the effects of imatinib on skin stiffness in vivo with optical coherence elastography

Harshdeep Singh Chawla1, Yanping Chen1, Jessica Gutiarez1, Chandra Mohan1, Fernando Zvietcovich1, Manmohan Singh1, Salavat R. Aglyamov2, and Kirill V. Larin1,3,
1Biomedical Engineering, University of Houston, 3517 Cullen Blvd, Houston, TX 77204
2Mechanical Engineering, University of Houston, 4726 Calhoun Rd, Houston, TX 77204
3Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030

Abstract

Systemic sclerosis (SSc-scleroderma) is a rare, chronic autoimmune rheumatic disease that is associated with widespread degenerative changes and scarring of the skin, joints, and internal organs as well as abnormalities in blood vessels. SSc has a standardized mortality ratio of 3.5, which is the highest disease-related mortality among major rheumatic diseases. SSc can also be characterized by a change in the texture and appearance of the skin. This happens due to increased collagen production and is one of the main causes of distress. There is currently no clinically approved treatment or even objective assessment for SSc skin involvement. The modified Rodnan Skin Score (mRSS) is determined by palpation on 17 parts of the body. mRSS also requires extensive training and experience for accurate assessments but is currently the standard assessment method for skin involvement in SSc. Moreover, it shows a very high variability between observers and is very subjective and confused by multiple parameters. Optical coherence elastography (OCE) is an established technique that can assess mechanical contrast in tissues with a micrometer spatial resolution. In this work, OCE was used to non-invasively assess the mechanical properties of mouse skin in vivo. OCE measurements were performed on 3 groups of mice, (1) control group that was injected with PBS, (2) SSc group that was injected with bleomycin (BLM), and (3) treatment group that was first injected with BLM and then injected with imatinib. Imatinib is postulated to reduce SSc involvement. An air-coupled ultrasound transducer induced low amplitude elastic waves in the anesthetized dorsal mouse skin after removal of hair. A phase-stabilized swept source OCE system detected the waves, and the group velocity was quantified from the OCE measurements. The wave velocity of the BLM-SSc skin was significantly higher than that of normal skin (p<0.05), corresponding to a greater stiffness. The wave speed in the treatment group was between the stiffness of the control group and BLM group, indicating a slight softening of the skin due to the treatment. Thus, showing the ability of OCE to differentiate healthy and fibrotic skin completely non-invasively.

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Harshdeep Singh Chawla
University of Houston
United States of America

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