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PURPOSE The purpose of this study was to evaluate the efficacy of radiomics derived from slice-reduced CT (srCT) scans versus full-chest CT (fcCT) for diagnosing and staging of interstitial lung disease (ILD) in systemic sclerosis (SSc), considering the potential to reduce radiation exposure. MATERIAL AND METHODS The fcCT corresponded to a standard high-resolution full-chest CT whereas the srCT consisted of nine axial slices. 1451 radiomic features in two dimensions from srCT and 1375 features in three dimensions from fcCT scans were extracted from 166 SSc patients. The study included first- and second-order features from original and wavelet-transformed images. We assessed the predictive performance of quantitative CT (qCT)-based logistic regression (LR) models relying on preselected features and machine learning workflows involving LR and extra-trees classifiers with data-driven feature selection. The area under the receiver operating characteristic curve (AUC) was used to estimate model performance. RESULTS The best models for diagnosis and staging ILD achieved AUC=0.85±0.08 and AUC=0.82±0.08 with srCT, and AUC=0.83±0.06 and AUC=0.76±0.08 with fcCT, respectively. srCT-based models showed slightly superior performance over fcCT-based models, particularly in 2D-radiomic analyses when interpolation resolution closely matched the original in-plane resolution. For diagnosis, the LR outperformed qCT-models, whereas for staging, the best results were obtained with a qCT-based model. CONCLUSIONS Radiomics from srCT is an effective and preferable alternative to fcCT for diagnosing and staging SSc-ILD. This approach not only enhances predictive accuracy but also minimizes radiation exposure risks, offering a promising avenue for improved treatment decision support in SSc-ILD management.

Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.

BACKGROUND Interstitial lung disease (ILD) defines a group of parenchymal lung disorders, characterized by fibrosis as their common final pathophysiological stage. To improve diagnosis and treatment of ILD, there is a need for repetitive non-invasive characterization of lung tissue by quantitative parameters. In this study, we investigated whether CT image patterns found in mice with bleomycin induced lung fibrosis can be translated as prognostic factors to human patients diagnosed with ILD. METHODS Bleomycin was used to induce lung fibrosis in mice (n_control = 36, n_experimental = 55). The patient cohort consisted of 98 systemic sclerosis (SSc) patients (n_ILD = 65). Radiomic features (n_histogram = 17, n_texture = 137) were extracted from microCT (mice) and HRCT (patients) images. Predictive performance of the models was evaluated with the area under the receiver-operating characteristic curve (AUC). First, predictive performance of individual features was examined and compared between murine and patient data sets. Second, multivariate models predicting ILD were trained on murine data and tested on patient data. Additionally, the models were reoptimized on patient data to reduce the influence of the domain shift on the performance scores. RESULTS Predictive power of individual features in terms of AUC was highly correlated between mice and patients (r = 0.86). A model based only on mean image intensity in the lung scored AUC = 0.921 ± 0.048 in mice and AUC = 0.774 (CI95% 0.677-0.859) in patients. The best radiomic model based on three radiomic features scored AUC = 0.994 ± 0.013 in mice and validated with AUC = 0.832 (CI95% 0.745-0.907) in patients. However, reoptimization of the model weights in the patient cohort allowed to increase the model's performance to AUC = 0.912 ± 0.058. CONCLUSION Radiomic signatures of experimental ILD derived from microCT scans translated to HRCT of humans with SSc-ILD. We showed that the experimental model of BLM-induced ILD is a p

Single cell mRNA sequencing of the whole organ has become a popular technique to reveal rare types and subtypes of previously characterized cells as well as to distinguish and characterize gene expression of previously unknown cell types. Unsupervised clustering can reveal tens or even hundreds of variable genes that characterize cell types. Variation in gene expression is often observed within one cell type, and sometimes cannot be biologically explained without mapping of mRNA on tissue. In this study we aim to (i) map the majority of cell types of human lung, (ii) describe variability in their gene expression and (iii) relate this gene expression to cellular location and neighborhoods. Using three different spatial transcriptomics approaches, we mapped epithelial cell states of airways and submucosal gland, and defined cell type-unrelated gene expression variability along proximo-distal axis, including potential regulators and co-regulators of such cell states in the mesenchymal and immune cell niches. In addition, we mapped rare cell types, such as subtypes of neuroendocrine cells, ionocytes and tuft (brush) cells, revealing tracheal preference for ionocytes, and distal airways for GHRL-positive neuroendocrine cells. Finally, we used the created map as a reference for the diseased tissue from patients with stage II COPD and revealed perturbed cell states and COPD-specific imbalance of cell types, affecting immune and AT0 clusters.