Harmonizing the National Lung Screening Trial: Kernel resolution and field of view compensation

Low-dose chest computed tomography scans acquired in multi-centre studies exhibit heterogeneity in the form of varying spatial resolution, reconstruction kernel and semantic field-of-view that hinder the reproducibility of quantitative measures and generalizability of downstream analyses. The National Lung Screening Trial (NLST) provides a large, open collection of low-dose chest CT scans characterized by heterogeneous spatial resolution, reconstruction kernels and field-of-view configurations. This diversity presents an opportunity to standardize the data, enabling reproducible biomarker estimation and broader reuse of the NLST as a homogeneous quantitative imaging resource. In this work, we present a standardization pipeline that was applied to 105,191 scans from 23,669 participants in the NLST. The pipeline addresses the following elements: (1) Resampling through-axial-plane (z) spatial resolution to 1.0 mm (2) Harmonization of reconstruction kernels across intra-vendor (paired) and inter-vendor (unpaired) settings using an anatomy guided multipath cycleGAN where scans were mapped to a reference Siemens B30f (soft) and Siemens B50f (hard) kernel (3) Semantic field-of-view extension across all scans. Quantitative consistency across percent emphysema and body composition assessment (skeletal muscle and subcutaneous adipose tissue volumes) was evaluated in paired, cross-sectional and longitudinal settings. For paired data, harmonization improved agreement of quantitative measures relative to the soft kernel reference. Cross-sectional analyses demonstrated reduced inter-kernel variability, with small to medium effect sizes (Cohen's d = 0.2 to 0.5) for percent emphysema and improved correlations with anthropometric measures post field-of-view extension. Longitudinal analysis using linear mixed effect models, showed reduced kernel bias and improved longitudinal consistency of biomarkers reflected by the increase in intraclass correlation coefficients. This work provides a harmonized NLST imaging resource that enables consistent and reliable quantitative biomarker estimation for lung cancer screening, with open source code released at https://github.com/MASILab/Harmonized_NLST_dataset and the harmonized dataset to be made publicly available once data return to the NLST is completed.