Quantitative comparative analysis of different CT modalities in systemic sclerosis-associated interstitial lung disease: correlations with lung function, serological biomarkers, and disease stratification.

Background: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) represents a major cause of morbidity and mortality among patients with systemic sclerosis, underscoring the need for early and accurate assessment of pulmonary fibrosis. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) currently constitute the primary tools for diagnosis and disease evaluation. However, qualitative interpretation of HRCT is limited in its ability to provide objective quantification of fibrosis severity, and PFTs may be unreliable or impractical in patients with advanced disease or inadequate respiratory cooperation. Emerging quantitative computed tomography techniques, including monoenergetic 70 keV computed tomography (MonoE 70 keV CT) and virtual non-contrast computed tomography (VNC CT), have demonstrated potential for enhanced tissue characterization; nevertheless, their clinical applicability and comparative performance in SSc-ILD remain insufficiently established. Accordingly, this study aimed to systematically evaluate and compare quantitative parameters derived from HRCT, MonoE 70 keV CT, and VNC CT, and to examine their associations with pulmonary function, serological biomarkers, and disease stratification in patients with SSc-ILD. Methods: This retrospective study enrolled 43 patients with SSc-ILD who underwent HRCT, MonoE 70 keV CT, VNC CT, pulmonary function testing, and laboratory assessments. Quantitative radiomic parameters, including attenuation, standard deviation (SD), skewness, and kurtosis, were extracted. Correlations between CT parameters and pulmonary function indices were evaluated using Pearson or Spearman correlation analyses, and K-means clustering was applied to stratify patients based on imaging features. Results: HRCT demonstrated the highest SD, whereas VNC CT showed the lowest (P<0.05). Quantitative CT parameters correlated significantly with pulmonary function indices: attenuation and SD were negatively correlated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) (-0.41<R<-0.30, P<0.05), while skewness and kurtosis were positively correlated with lung volume parameters (0.35<R<0.45, P<0.01). All three CT modalities stratified patients into two clusters, with Cluster 1 reflecting more advanced fibrosis. VNC CT-based clustering revealed differences in anti-Scl-70 antibody levels, whereas MonoE 70 keV CT was particularly sensitive in assessing residual volume (RV) and functional residual capacity by plethysmography (FRCpleth). Conclusions: HRCT, MonoE 70 keV CT, and VNC CT exhibit distinct and complementary advantages in the assessment of SSc-ILD. Quantitative CT parameters reflect disease severity, with MonoE 70 keV CT demonstrating strengths in lung volume analysis and VNC CT showing potential value in serological disease activity assessment, thereby supporting diagnosis and individualized disease management.