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The secondary aim was to identify a suitable pharmacokinetic model configuration for anisotropic temporally-spaced DCE-MRI sequences, considering Tofts variants, population-averaged arterial input functions (AIF), and bolus arrival time (BAT) estimation methods.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Materials and methods<\/jats:title>\n            <jats:p>From April 2021 to May 2023, patients with locally advanced non-small cell lung cancer (NSCLC) were prospectively enrolled. Tumors were categorized based on: PD-L1 absence\/presence (threshold 1%) and hyperexpression\/hypoexpression (threshold 50%). Pharmacokinetic parameters were extracted using several candidate configurations; fit quality was evaluated using coefficient of determination (<jats:italic>R<\/jats:italic>\u00b2). Mann\u2013Whitney U-test and ROC-AUC were used to assess correlation with PD-L1 for the best-fit configuration.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Thirty-eight patients (mean age 68\u2009\u00b1\u20099 years, 28 men) were included. PD-L1 expression was present in 25 patients (66%) and absent in 13 (34%). PD-L1 was hyperexpressed in 13 (34%) patients and hypoexpressed in 25 (66%). Voxel-wise pharmacokinetic parameters were extracted using the best-fit configuration\u2014extended Tofts model (ETM) with Georgiou AIF and Peak-Gradient (PG) BAT estimation (<jats:italic>R<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.79). K<jats:sup>trans<\/jats:sup> median (0.25 vs. 0.12\u2009min<jats:sup>\u2212<\/jats:sup>\u00b9, <jats:italic>p<\/jats:italic>\u2009=\u20090.02), K<jats:sup>trans<\/jats:sup> standard deviation (0.32 vs. 0.23\u2009min<jats:sup>\u2212<\/jats:sup>\u00b9, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and K<jats:sub>ep<\/jats:sub> median (1.09 vs. 0.59\u2009min<jats:sup>\u2212<\/jats:sup>\u00b9, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) were significantly higher in PD-L1\u2009&lt;\u200950% group (ROC-AUC 0.71\u20130.76).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>DCE-MRI pharmacokinetic parameters could stratify PD-L1 hypo\/hyperexpression in NSCLC. The ETM with PG BAT estimation method and Georgiou AIF was the best-performing pharmacokinetic configuration.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key Points<\/jats:title>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Question<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>Could Dynamic Contrast-Enhanced (DCE) MRI offer a safe and non-invasive way to assess Programmed Death-Ligand 1 (PD-L1) expression?<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Findings<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>Quantitative DCE-MRI parameters K<\/jats:italic>\n              <jats:sup>trans<\/jats:sup> (the volume transfer rate) and K<jats:sub>ep<\/jats:sub> (the efflux rate constant) show potential for distinguishing PD-L1 hyperexpression from hypoexpression.<\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Clinical relevance<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>Preliminary results suggest that DCE-MRI could be a safe method to stratify PD-L1 hypo\/hyperexpression in non-small cell lung cancer, potentially optimizing treatment decisions, given the high cost of immunotherapy.<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00330-025-11524-1","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:12:23Z","timestamp":1743293543000},"page":"5569-5580","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Non-invasive PD-L1 stratification in non-small cell lung cancer using dynamic contrast-enhanced MRI"],"prefix":"10.1007","volume":"35","author":[{"given":"Gaia","family":"Messana","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra","family":"Bortolotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-9949","authenticated-orcid":false,"given":"Sithin","family":"Thulasi Seetha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Marrocco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Pairazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Sanvito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Brero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnese","family":"Robustelli Test","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella Fiamma","family":"Cabini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Lascialfari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Zac\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia Maria","family":"Stella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Agustoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Saddi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Riccardo","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Preda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"11524_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Outside the submitted work, he has received institutional grants from AstraZeneca, Merck Sharp Dohme, and Hoffmann-La Roche. He discloses receiving consultation fees from AstraZeneca and Radiomics.bio, and honoraria for lectures, presentations, or educational events from AstraZeneca, Hoffmann-La Roche, and Takeda. AstraZeneca and Elekta have also provided support for attending meetings and\/or travels. D.Z. reports no conflicts of interest in this study but discloses his employment with Siemens Healthcare s.r.l. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"No complex statistical methods were necessary for this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Fondazione IRCCS Policlinico San Matteo (protocol code P_20190113422 approved on February 10, 2021).","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}