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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\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20090.2 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\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/MASILab\/Harmonized_NLST_dataset\" xlink:type=\"simple\">https:\/\/github.com\/MASILab\/Harmonized_NLST_dataset<\/jats:ext-link>\n                    and the harmonized dataset to be made publicly available once data return to the NLST is completed.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352075","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:40:16Z","timestamp":1791222016000},"page":"e0352075","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harmonizing the National Lung Screening Trial: Kernel resolution and field of view compensation"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1829-8245","authenticated-orcid":true,"given":"Aravind R.","family":"Krishnan","sequence":"first","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Kim","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Computer Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Rudravaram","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1332-5762","authenticated-orcid":true,"given":"Trent","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8565-8191","authenticated-orcid":true,"given":"Andre T. S.","family":"Hucke","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas W.","family":"Remedios","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Z.","family":"Li","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Biomedical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Xu","sequence":"additional","affiliation":[{"name":"Insitro","place":["South San Francisco, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim L.","family":"Sandler","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Department of Radiology and Radiological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yency Forero","family":"Martinez","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Antic","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Department of Medicine"]},{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Department of Thoracic Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianrui","family":"Zuo","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett A.","family":"Landman","sequence":"additional","affiliation":[{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Electrical and Computer Engineering"]},{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Computer Science"]},{"name":"Vanderbilt University","place":["Nashville, Tennessee, United States of America"],"department":["Department of Biomedical Engineering"]},{"name":"Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"],"department":["Department of Radiology and Radiological Sciences"]},{"name":"Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center","place":["Nashville, Tennessee, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"pone.0352075.ref001","unstructured":"Naidich DP, Marshall CH, Gribbin C, Arams RS, Mccauley DI. 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