{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:19:00Z","timestamp":1786976340061,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Applied Clin Med Phys"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Methods have been developed that apply image processing to 4DCTs to generate 4DCT\u2010ventilation\/perfusion lung imaging. Traditional methods for 4DCT\u2010ventilation rely on Hounsfield\u2010Unit (HU) density\u2010change methods and suffer from poor numerical robustness while not providing 4DCT\u2010perfusion data. The purpose of this work was to evaluate the clinical differences between classic HU\u2010based 4DCT\u2010ventilation approaches and novel 4DCT\u2010ventilation\/perfusion approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 63 lung cancer patients enrolled in a functional avoidance clinical trial were analyzed. 4DCT\u2010data were used to generate four lung\u2010function images: (1) classical HU\u2010based 4DCT\u2010ventilation (\u201c4DCT\u2010vent\u2010HU\u201d), and three novel, statistically robust methods: (2) 4DCT\u2010ventilation based on the Mass Conserving Volume Change (\u201c4DCT\u2010vent\u2010MCVC\u201d), (3) 4DCT\u2010ventilation using the Integrated Jacobian Formulation, and (4) 4DCT\u2010perfusion. A radiologist reviewed all images for ventilation\/perfusion defects (scored as yes\/no) and the scores for the novel approaches were compared to those of 4DCT\u2010vent\u2010HU using receiver operating characteristic (ROC) analysis. Functional contours were generated using thresholding methods, and the contours from the three novel 4DCT\u2010ventilation methods were compared against that from 4DCT\u2010vent\u2010HU (Dice similarity coefficients [DSC]). Functional mean lung dose (fMLD) and dose\u2010function metrics were compared against dose\u2010function metrics using 4DCT\u2010vent\u2010HU.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ROC analysis revealed accuracy in the range of 0.55 to 0.73 comparing radiologist interpretations of 4DCT\u2010vent\u2010HU against the three novel approaches. Average DSC values were 0.41\u00a0\u00b1\u00a00.19, 0.44\u00a0\u00b1\u00a00.16, and 0.42\u00a0\u00b1\u00a00.17 comparing 4DCT\u2010vent\u2010HU to 4DCT\u2010vent\u2010IJF, 4DCT\u2010vent\u2010MCVC, and 4DCT\u2010perf, respectively. All novel imaging methods showed significant differences (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) in dose\u2010function metrics compared to those of 4DCT\u2010vent\u2010HU. 4DCT\u2010vent\u2010MCVC and 4DCT\u2010Perf depicted the smallest and largest differences from 4DCT\u2010vent\u2010HU in fMLD (3.51\u00a0\u00b1\u00a03.20\u00a0Gy and 5.90\u00a0\u00b1\u00a05.29\u00a0Gy, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first work to comprehensively compare novel 4DCT\u2010ventilation\/perfusion methods against classical formulations. Our data show that significant differences between the 4DCT\u2010based functional imaging methods exist, suggesting that studies are needed to evaluate which methods provide the most robust clinical results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acm2.70088","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:44:16Z","timestamp":1744159456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive clinical evaluation of novel 4DCT\u2010based lung function imaging methods"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-5998","authenticated-orcid":false,"given":"Ehsan","family":"Golkar","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Thomas Jefferson University  Philadelphia 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