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LSC-2024-Deciphering the Spatial Heterogeneity of Interstitial Lung Disease by Integrative Radiomics and Single-Nucleus Transcriptomics

EUROPEAN RESPIRATORY JOURNAL(2024)

Univ Bern | German Ctr Lung Res DZL | Katholieke Univ Leuven | Univ Zurich | Univ Antwerp

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Abstract
Spatial heterogeneity in disease patterns is a key hallmark of interstitial lung diseases (ILDs), such as systemic sclerosis (SSc)-ILD. High-dimensional image analysis (radiomics) of computed tomography (CT) scans offers quantitative insights into organ-scale pathophysiology, creating digital disease fingerprints. Here, we aimed to integrate spatially resolved radiomic profiles extracted from CT scans with matched molecular data to decipher the cellular programs underlying the spatial heterogeneity in ILDs and how they are reflected in radiomic phenotypes. We therefore systematically dissected a whole right lung of a SSc-ILD patient into 65 samples for virtual 3D alignment and association of regional radiomic profiles with CT co-localized histopathology and single-nucleus RNA sequencing (snRNAseq). Radiomic profiles significantly differed with spatial location revealing a typical apical to basal gradient characteristic for the spatial heterogeneity in SSc-ILD. To assess whether those radiomic differences translate to the molecular level, we performed snRNAseq, with 14 distal lung regions from apex to base. Analyzing 124,000 cells from more than 50 cell types we revealed region-specific alterations in cellular composition, gene expression and cell-cell communication networks. Integration of radiomics and transcriptomics data showed spatial radiomic modules with distinct cellular profiles, including an apical T cell exhaustion and a basal macrophage-driven fibrogenic program. In conclusion, we provide an in-depth imaging and molecular phenotyping of the spatial heterogeneity of SSc-ILD, highlighting the potential of radiomics as virtual organ-scale biopsies.
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Key words
High-Resolution CT,Medical Imaging,Spectral Imaging,Radiomics,Cancer Imaging
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要点】:本文通过整合放射组学和高分辨率单核转录组学技术,揭示了系统性硬化病相关间质性肺病(SSc-ILD)的空间异质性及其背后的细胞程序。

方法】:作者采用高维图像分析(放射组学)从CT扫描中提取空间分辨的放射组学特征,并将其与匹配的分子数据相结合。

实验】:通过对一名SSc-ILD患者的整个右肺进行65个样本的分离、虚拟3D对齐,以及与CT同位素组织病理学及单核RNA测序(snRNAseq)的关联分析,发现放射组学特征随空间位置显著变化,呈现从顶部到底部的梯度特征。作者进一步对从肺尖到肺底部的14个远端肺区域进行了snRNAseq,分析超过50种细胞类型的124,000个细胞,揭示了区域特定的细胞组成、基因表达和细胞间通讯网络的改变。放射组学与转录组学数据的整合揭示了具有不同细胞特征的空间放射组学模块。