{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:36Z","timestamp":1792789176359,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["R01HL170149"],"award-info":[{"award-number":["R01HL170149"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R01HL170149"],"award-info":[{"award-number":["R01HL170149"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objective: To evaluate the ability of a physiologically derived post-trigger delay (PTD) model to predict pulmonary arterial peak enhancement timing using human dynamic CT perfusion data and to compare physiologically derived PTD estimates with commonly used fixed-delay protocols. Methods: In this retrospective study, 39 patients who underwent dynamic pulmonary CT perfusion imaging were evaluated. Pulmonary arterial enhancement curves were generated from the main pulmonary artery (MPA) using attenuation measurements obtained from 19 dynamic CT volume scans and fitted using a gamma-variate function. Reference peak enhancement timing was determined from the fitted enhancement curves. A physiologically derived PTD was calculated using a previously established relationship incorporating contrast injection duration and a dispersion component derived from first-pass contrast transport dynamics. Fixed PTD protocols of 4, 5, 6, and 7 s were evaluated as reference benchmarks. Enhancement and contrast-to-noise ratio (CNR) measurements were obtained in the MPA and five lobar pulmonary arteries. Protocol performance was assessed relative to the reference standard using nonparametric statistical testing, regression analysis, and Bland\u2013Altman analysis, with enhancement and CNR measurements summarized as median [interquartile range] and paired differences reported with 95% confidence intervals. Results: The mean physiologically derived PTD was 5.06 s, compared with a mean reference PTD of 5.18 s. In the MPA, the median absolute enhancement difference relative to the reference was 1.02 HU (95% CI, 0.42\u20134.66) for the physiologically derived PTD, compared with 50.76 HU (35.53\u201366.88), 1.05 HU (0.48\u20138.35), 25.60 HU (17.95\u201340.34), and 114.66 HU (78.45\u2013138.55) for the 4-, 5-, 6-, and 7-s fixed-delay protocols, respectively. The corresponding median absolute CNR differences were 0.02 (0.01\u20130.10), 0.89 (0.67\u20131.23), 0.02 (0.01\u20130.16), 0.51 (0.32\u20130.78), and 1.96 (1.46\u20132.67). The physiologically derived PTD demonstrated significantly smaller differences from the reference than the 4-, 6-, and 7-s protocols (Holm-adjusted p &lt; 0.05), with no significant difference compared with the 5-s protocol. Regression and Bland\u2013Altman analyses demonstrated strong agreement with the reference standard. Conclusions: A physiologically derived PTD demonstrated strong agreement with retrospectively determined pulmonary arterial peak enhancement timing in this human cohort. While performance was similar to a fixed 5-s delay under the relatively standardized injection conditions used in this study, the findings support the applicability of a previously established physiologic PTD relationship to human pulmonary arterial enhancement and provide validation of the model using human dynamic CT data.<\/jats:p>","DOI":"10.3390\/diagnostics16183033","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient-Specific Timing for Pulmonary CT Angiography: Human Validation of a Physiologically Derived Post-Trigger Delay Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3903-3526","authenticated-orcid":false,"given":"Kyrillos","family":"Grace","sequence":"first","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Neda","family":"Ziaei","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7836-5258","authenticated-orcid":false,"given":"Lynn","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Alireza","family":"Shojazadeh","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3625-5166","authenticated-orcid":false,"given":"Liqiang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-8050","authenticated-orcid":false,"given":"Cecilia","family":"Brewington","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Sabee","family":"Molloi","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s11548-010-0526-4","article-title":"CTPA as the gold standard for the diagnosis of pulmonary embolism","volume":"6","author":"Oldham","year":"2011","journal-title":"Int. J. Comput. Assist. Radiol. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.21037\/cdt.2017.12.01","article-title":"Imaging of acute pulmonary embolism: An update","volume":"8","author":"Moore","year":"2018","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.7326\/M14-1772","article-title":"For the Clinical Guidelines Committee of the American College of Physicians. Evaluation of Patients with Suspected Acute Pulmonary Embolism: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians","volume":"163","author":"Raja","year":"2015","journal-title":"Ann. Intern Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.rcl.2008.10.009","article-title":"Optimal vascular and parenchymal contrast enhancement: The current state of the art","volume":"47","author":"Fleischmann","year":"2009","journal-title":"Radiol. Clin. North Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21602167","DOI":"10.1161\/01.CIR.0000128813.04325.08","article-title":"Spiral Computed Tomography for Acute Pulmonary Embolism","volume":"109","author":"Schoepf","year":"2004","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"W260","DOI":"10.2214\/AJR.10.5814","article-title":"Cardiothoracic CT angiography: Current contrast medium delivery strategies","volume":"196","author":"Weininger","year":"2011","journal-title":"Am. J. Roentgenol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.rcl.2024.01.005","article-title":"Computed Tomography Angiography: Principles and Advances","volume":"62","author":"Szczykutowicz","year":"2024","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2214\/AJR.06.1240","article-title":"CT pulmonary angiography and CT venography: Factors associated with vessel enhancement","volume":"189","author":"Arakawa","year":"2007","journal-title":"Am. J. Roentgenol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jmir.2020.06.002","article-title":"Weight-Adjusted Contrast Administration in the Computed Tomography Evaluation of Pulmonary Embolism","volume":"51","author":"Ratnakanthan","year":"2020","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jmir.2011.05.002","article-title":"Contrast medium administration and parameters affecting bolus geometry in multidetector computed tomography angiography: An overview","volume":"42","author":"Saade","year":"2011","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1007\/s00330-008-1100-0","article-title":"Quality of CT pulmonary angiography for suspected pulmonary embolus in pregnancy","volume":"18","author":"Freeman","year":"2008","journal-title":"Eur. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340.e9","DOI":"10.1016\/j.crad.2016.11.018","article-title":"Analysis of contrast time\u2013enhancement curves to optimise CT pulmonary angiography","volume":"72","author":"Zhu","year":"2017","journal-title":"Clin. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e243833","DOI":"10.1148\/radiol.243833","article-title":"Optimal Approach to Performing and Reporting Computed Tomography Angiography for Suspected Acute Pulmonary Embolism: A Clinical Consensus Statement of the ESC Working Group on Pulmonary Circulation & Right Ventricular Function, the Fleischner Society, the Association for Acute Cardiovascular Care (ACVC) and the European Association of Cardiovascular Imaging (EACVI) of the ESC, Endorsed by European Respiratory Society (ERS), Asian Society of Thoracic Radiology (ASTR), European Society of Thoracic Imaging (ESTI), and Society of Thoracic Radiology (STR)","volume":"315","author":"Klok","year":"2025","journal-title":"Radiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1148\/radiol.10090908","article-title":"Intravenous contrast medium administration and scan timing at CT: Considerations and approaches","volume":"256","author":"Bae","year":"2010","journal-title":"Radiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E60","DOI":"10.1007\/s10406-005-0166-x","article-title":"How to design injection protocols for multiple detector-row CT angiography (MDCTA)","volume":"15","author":"Fleischmann","year":"2005","journal-title":"Eur. Radiol. Suppl."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Higaki, T., Nakaura, T., Kidoh, M., Yuki, H., Yamashita, Y., Nakamura, Y., Tatsugami, F., Baba, Y., Iida, M., and Awai, K. (2018). Effect of contrast material injection duration on arterial enhancement at CT in patients with various cardiac indices: Analysis using computer simulation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191347"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.2214\/AJR.05.0714","article-title":"MDCT angiography of the pulmonary arteries: Influence of body weight, body mass index, and scan length on arterial enhancement at different iodine flow rates","volume":"187","author":"Schoellnast","year":"2006","journal-title":"Am. J. Roentgenol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lell, M.M., Fleischmann, U., Pietsch, H., Korporaal, J.G., Haberland, U., Mahnken, A.H., Flohr, T.G., Uder, M., and Jost, G. (2017). Relationship between low tube voltage (70 kV) and the iodine delivery rate (IDR) in CT angiography: An experimental in-vivo study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173592"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/RLI.0000000000000119","article-title":"Optimizing contrast media injection protocols in state-of-the art computed tomographic angiography","volume":"50","author":"Lell","year":"2015","journal-title":"Investig. Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/jmrs.724","article-title":"A comparison of bolus track and test bolus computed tomography pulmonary angiography and the implications on pulmonary and aortic vessel enhancement, effective dose and suboptimal scan rate","volume":"71","author":"Murphy","year":"2024","journal-title":"J. Med. Radiat. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejrad.2010.06.023","article-title":"Dual-energy CT angiography of the lungs: Comparison of test bolus and bolus tracking techniques for the determination of scan delay","volume":"81","author":"Henzler","year":"2012","journal-title":"Eur. J. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/jmrs.17","article-title":"A retrospective comparison of smart prep and test bolus multi-detector CT pulmonary angiography protocols","volume":"60","author":"Suckling","year":"2013","journal-title":"J. Med. Radiat. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"539","DOI":"10.6009\/jjrt.2024-1385","article-title":"Usefulness of Delay Time Setting in Computed Tomography Pulmonary Angiography","volume":"80","author":"Kuramochi","year":"2024","journal-title":"Jpn. J. Radiol. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s41747-019-0093-6","article-title":"Timing optimization of low-dose first-pass analysis dynamic CT myocardial perfusion measurement: Validation in a swine model","volume":"3","author":"Hubbard","year":"2019","journal-title":"Eur. Radiol. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1038\/s41598-022-12016-8","article-title":"Contrast timing optimization of a two-volume dynamic CT pulmonary perfusion technique","volume":"12","author":"Zhao","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","first-page":"100036","article-title":"A patient-specific timing protocol for improved CT pulmonary angiography","volume":"8","author":"Zhao","year":"2023","journal-title":"Res. Diagn. Interv. Imaging"},{"key":"ref_27","unstructured":"American Association of Physicists in Medicine (2008). The Measurement, Reporting, and Management of Radiation Dose in CT, American Association of Physicists in Medicine. AAPM Report No. 96."},{"key":"ref_28","first-page":"194","article-title":"Canadian Society of Thoracic Radiology\/Canadian Association of Radiologists Best Practice Guidance for Investigation of Acute Pulmonary Embolism, Part 1: Acquisition and Safety Considerations","volume":"73","author":"Nguyen","year":"2022","journal-title":"Can. Assoc. Radiol. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.25259\/JCIS_51_2022","article-title":"Optimizing low contrast volume thoracic CT angiography: From the basics to the advanced","volume":"12","author":"Hobbs","year":"2022","journal-title":"J. Clin. Imaging Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.acra.2023.05.018","article-title":"Minimizing Contrast Media Dose in CT Pulmonary Angiography with Clinical Photon Counting Using High Pitch Technique","volume":"31","author":"Saeed","year":"2024","journal-title":"Acad. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1007\/s00330-025-12054-6","article-title":"Reducing contrast media dosage for pulmonary embolism CTPA in PCD-CT: A comparative study of EID-CT and PCD-CT in the era of individualized protocolling","volume":"36","author":"Stammen","year":"2025","journal-title":"Eur. Radiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1007\/s00330-013-3067-8","article-title":"Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: A pilot study","volume":"24","author":"Pienn","year":"2014","journal-title":"Eur. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1016\/j.crad.2022.11.007","article-title":"CT pulmonary angiography: Optimising acute thoracic imaging by fixed-timing contrast medium delivery with a modified breathing instruction","volume":"78","author":"Neumann","year":"2023","journal-title":"Clin. Radiol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/18\/3033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:16:21Z","timestamp":1790050581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/18\/3033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":33,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16183033"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16183033","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}