Radiomic Profiling of Chest CT in a Cohort of Sarcoidosis Cases

Background High resolution computed tomography (HRCT) of the chest is increasingly used in clinical practice for sarcoidosis. Visual assessment of chest HRCTs in patients with sarcoidosis has high inter- and intra-rater variation. Radiomics offers a reproducible quantitative assessment of HRCT lung parenchyma and could be useful as an additional summary measure of disease. We develop radiomic profiles on HRCT and map them to radiologic, clinical, and patient reported outcomes. Research Question Can radiomic analysis of chest HRCT cluster patients into groups that are related to radiologic, clinical, and patient reported outcomes? Study Design and Methods Three-dimensional radiomic features were calculated on chest HRCT for both lungs from sarcoidosis cases enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study (N=320). Robust and sparse K-means was used to cluster sarcoidosis cases using their radiomic profiles. Differences in patterns on visual assessment (VAS) by cluster were identified using chi-squared tests. Linear regression investigated how pulmonary function tests and patient reported outcomes differed between clusters with and without adjustment for other radiologic quantification. Results Radiomic-based clustering identified four clusters associated with both Scadding stage and Oberstein score ( P <0.001). One of the clusters had markedly few abnormalities. Another cluster had consistently more abnormalities along with more Scadding stage IV. Average pulmonary function testing (PFT) differed between clusters, even after accounting for Scadding stage and Oberstein score ( P <0.001), with one cluster having more obstructive disease. The most discriminative radiomic measures explained 10-15% of the variation in PFT beyond demographic variables. Shortness of breath, fatigue, and physical health differed by cluster ( P <0.014). Interpretation Radiomic quantification of sarcoidosis identifies new subtypes representative of existing radiologic assessment and more predictive of pulmonary function. These findings provide evidence that radiomics may be useful for identifying new imaging-based disease phenotypes. ### Competing Interest Statement NEC, WLL, MM, TEF, SL, BB, TEF have received grants from the National Institutes of Health (R01 HL114587; R01 HL142049; U01 HL112695; U01 HL112707; U01 HL112707, U01 HL112694, U01 HL112695, U01 HL112696, U01 HL112702, U01 HL112708, U01 HL112711, U01 HL112712) WLL is additionally support on National Institutes of Health 5T32HL007085 LAM has received grants from the National Institute of Health (R01HL140357, R01HL142049, R01 HL114587; U01 HL112695; U01 HL112707; U01 HL112707, U01 HL112694, U01 HL112695, U01 HL112696, U01 HL112702, U01 HL112708, U01 HL112711, U01 HL112712, and R01HL136681), Ann Theodore Foundation, the FSR, Mallinckrodt Pharmaceuticals, and the University of Cincinnati (Mallinckrodt Pharmaceuticals Foundation Grant) and serves on the Scientific Advisory Board for FSR, and Boeringer Ingelheim. ### Funding Statement This work is supported by NIH grants: R01 HL114587; R01 HL142049; U01 HL112695; U01 HL112707; U01 HL112707, U01 HL112694, U01 HL112695, U01 HL112696, U01 HL112702, U01 HL112708, U01 HL112711, U01 HL112712 and 5T32HL007085 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Colorado Multiple Institutional Review Board gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data is available via the process laid out by the GRADS consortium. * AD : Airway and Vascular Distortion BMI : body mass index BVB : bronchovascular bundle HRCT : High resolution chest computed tomography CXR : chest X-ray DLCO : diffusing capacity for carbon monoxide FEV1 : forced expiratory volume in one second FEV1/FVC : ratio of FEV1 to FVC FVC : forced vital capacity GIC : Genetics and Informatics Core GLCM : Gray level co-occurrence matrix GRADS : Genomic Research in Alpha-1 Anti-trypsin Deficiency and Sarcoidosis IRB : institutional review board LN : lymphadenopathy PA : parenchymal abnormalities PFT : Pulmonary Function Test QOL : Quality of life VAS : visual assessment score