Background/Purpose: Assessing skin involvement in systemic sclerosis (SSc) is complex, with no single method capturing all pathological changes. The modified Rodnan Skin Score (mRSS) is subjective, requires experienced assessors, and has notable inter-observer variability. Our initial studies showed that Spatial Frequency Domain Imaging (SFDI), an objective, noninvasive optical imaging modality, correlates with mRSS and has higher inter-rater reliability. However, the specific aspects of skin pathology measured by this technique remain unclear, as does its ability to track longitudinal changes. In this study, we systematically compare SFDI to mRSS, histology (gold-standard), ultrasound (for thickness), and durometry (for stiffness), and evaluate its longitudinal changes against changes in mRSS.

Methods: SSc patients and controls where enrolled under an IRB approved protocol. SFDI parameters (μs′ and Rd at 0.2 mm⁻¹ and 851 nm) were recorded at six sites: fingers, hands, and forearms. High-frequency ultrasound, durometry, and skin biopsies were done at the dorsal forearm. Two dermatopathologists evaluated histological sections for dermal thickness, alpha smooth muscle actin(ASMA)-positive fibroblast scoring, and other features. Collagen fiber score and trichrome quantification via ImageJ were also assessed. All measurements were performed blinded to clinical data. SFDI values were analyzed and compared across mRSS-defined groups using linear mixed models; clinical and histologic measurements were compared using one-way ANOVA with post-hoc Tukey tests, and correlations were assessed by Spearman’s method.

Results: 37 SSc patients and 18 controls who had skin biopsies along with SFDI measurements were included in the study. Longitudinal measurements were taken in 16 patients. Histology showed similar dermal and epidermal thickness between groups, while SSc patients had more dermal fibrosis, pigment incontinence, higher collagen and ASMA scores (Figure 1). SFDI parameters (μs′ and Rd) showed significant correlations with histology – including trichrome, ASMA, and collagen fiber scores – that closely matched those of mRSS. For clinical measures, SFDI correlated with ultrasound to a similar degree as mRSS, but did not perform as well as mRSS for durometry, though associations remained significant (Table 1). Additionally, SFDI measurements were significantly lower in SSc patients with mRSS = 0 compared to controls and declined further with increasing mRSS. Analysis of longitudinal changes revealed a strong correlation between changes in SFDI (∆Rd and ∆μs′) and changes in mRSS (∆mRSS) in Figure 2.

Conclusion: Our study shows that SFDI parameters exhibit face, content, and criterion validity comparable to mRSS when benchmarked against skin biopsy and other clinical metrics, supporting its use as a noninvasive, objective tool. SFDI also tracks longitudinal skin changes in SSc patients, making it versatile for monitoring disease progression and treatment response. Given its objectivity and minimal training requirements, SFDI is promising as a practical clinical tool, but further validation in longitudinal and multicenter studies is needed.

Figure 1. Overview of study design, cohort demographics, and histologic features. (A) Diagram depicting the SFDI technology and clinical assessments. (B) Demographic and clinical summary of enrolled patients. (C) Histology assessments in systemic sclerosis (SSc) and healthy controls. Collagen score was based on visual grading (0–3) of overall collagen fiber thickening on H&E-stained sections. ASMA – Alpha smooth muscle actin. ASMA score was assessed using a 0–3 visual analog scale (VAS), excluding adnexal and vascular structures. Trichrome staining was quantified via ImageJ color deconvolution (M = millions). Data are shown as median (Q1, Q3) or n (%). p < 0.05, p < 0.01, p < 0.001.

Table 1. Correlation between optical SFDI biomarkers and clinical/histologic measures of skin involvement. Spearman correlation coefficients (rₛ) and p-values are shown for reduced scattering (μs′), absorption (Rd), and mRSS with respect to clinical assessments (ultrasound, durometry) and histologic markers (collagen score, ASMA, trichrome). Collagen score was graded 0–3 based on dermal fiber thickening using the method developed by Dr. Jeff Browning at BUMC. ASMA was quantified on a 0–3 VAS scale based on α-SMA–positive fibroblasts, excluding adnexal/vascular structures. Trichrome intensity was quantified using ImageJ with color deconvolution. p < 0.05 considered significant.

Figure 2. (A) Baseline diffuse reflectance (Rd, left) and reduced scattering coefficient (μs′, right) significantly decreased with increasing modified Rodnan skin score (mRSS), with notable differences observed even between controls and patients with clinically uninvolved skin (mRSS = 0). Each dot represents an individual skin site (forearm, hand, or finger); black bars denote group medians. Asterisks indicate statistical significance based on Tukey’s post hoc test. (B) Longitudinal changes in Rd and μs′ were inversely correlated with changes in mRSS (ΔmRSS), indicating that optical properties increase in parallel with clinical improvement. Spearman correlation coefficients and p-values are shown.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/spatial-frequency-domain-imaging-sfdi-for-skin-assessment-in-systemic-sclerosis-insights-from-histology-and-clinical-correlates/