Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography

Abstract

Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young’s modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05 p<0.05 ). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

Fig. 1

Schematic of the PhS-SSOCE experimental setup that was used for studying BLM-induced SSc skin and healthy skin specimens.

Fig. 2

The air port tip was aligned with the OCE imaging plane from the OCT structural image: (a) 3-D OCT structural image from a typical healthy skin sample. The OCE measurement region is marked by the black arrows and the excitation position is marked by the black dot in the middle. (b) 2-D OCT image corresponding to black arrows in (a) with the OCE measurement positions being indicated by the colored solid dots. (c) Selected temporal vertical displacement profiles of the healthy skin sample, measured from the corresponding positions marked in (b) with matching colored solid dots. The black arrows in (c) indicate the temporal delay during the wave propagation.

Fig. 3

Histopathological features of BLM-induced skin fibrosis. Representative H&E stained skin sections from (a) PBS-injected control group specimen and (b) BLM-injected skin sample, at $100\times$ magnification. Compared to the PBS control group in (a), BLM-injected mice showed increased skin thickness, loss of subcutaneous fat tissue, as well as increased cellular infiltration. Representative sections stained with Masson’s trichrome at $100\times$ magnification from a (c) PBS-injected control group skin specimen and (d) BLM-treated sample. Thickened collagen bundles were observed in the BLM-injected mice, compared to the PBS-injected control mice. The scale bars represent the spatial distance of $100\mu \mathrm{m}$. The main features of the skin have been shown in (a) to (d), including fat tissue (1), hair follicles (2), inflammatory cells (3), and collagen (4). The skin thickness measurement is also shown in (a) and (b) by the double-headed red arrow; (e) skin thickness, (f) skin fibrosis score, and (g) skin hydroxyproline content were significantly higher in the BLM-SSc mice than in the control mice. Shown data are representative of similar findings from 18 mice from the control group and 13 mice from the BLM-SSc group.

Fig. 4

Typical OCT images of the healthy and SSc skin. The EDJ can be clearly identified in the healthy skin, as well the epidermis (E), and dermis (D) layers.

Fig. 5

Elastic wave propagation in the skin, as assessed by OCE. The displacement profiles of the healthy skin with color scale are plotted in (a). Depicted are the propagation profiles (Video 1) of the elastic wave in a typical healthy (top) and SSc (bottom) skin sample, measured at (b) 1.9 ms, (c) 3.03 ms, (d) 3.67 ms, (e) 4.4 ms, and (f) 5 ms after excitation from an in vivo sample imaged at the center region. The white triangle represents the reference signal used in the velocity calculations, and the white arrow indicates the propagation of the elastic wave (Video 1, MPEG 1 MB) [URL: http://dx.doi.org/10.1117/1.JBO.21.4.046002.1].

Fig. 6

In vivo OCE-assessment of skin involvement in the central regions of BLM-SSc-affected skin. Plotted are the Young’s modulus of the healthy skin and the central region of the BLM-SSc-afflicted skin from the in vivo OCE measurements, assessed in four mice per study group.

Fig. 7

In vitro and in vivo OCE assessment of skin involvement in the peripheral regions of BLM-SSc-affected skin. Plotted are the Young’s modulus recorded in healthy skin and BLM-SSc-afflicted skin at the periphery of the diseased region, from (a) in vitro and (b) in vivo OCE measurements.