{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:35:55Z","timestamp":1776836155090,"version":"3.51.2"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate assessment of lymph node status is essential for staging and treatment planning in breast cancer. Conventional morphological imaging criteria have limited sensitivity and specificity. Superparamagnetic Iron Oxide (SPIO)-enhanced MRI offers a functional imaging alternative exploiting macrophage-mediated iron uptake. This study evaluated the diagnostic performance of SPIO-enhanced MRI in differentiating metastatic from reactive hyperplastic lymph nodes and explored the association between MRI signal characteristics and Vascular Endothelial Growth Factor C (VEGF-C) expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty female breast cancer patients (January\u2013May 2024) underwent preoperative plain and SPIO-enhanced MRI (Resovist, 0.2\u202fmL\/kg, 12-h delay). Among 112 harvested lymph nodes, Hematoxylin and Eosin staining, Prussian Blue staining, and VEGF-C immunohistochemistry were performed. The Percentage of Signal Intensity Loss (PSIL) was calculated on T2*-weighted images. The primary diagnostic analysis was patient-level using mean PSIL with receiver operating characteristic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 112 lymph nodes from 60 patients, 47 were metastatic and 65 reactive hyperplastic. Reactive nodes showed marked signal attenuation (mean PSIL 64.7\u202f\u00b1\u202f12.0%) compared with metastatic nodes (11.6\u202f\u00b1\u202f7.8%;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Patient-level ROC analysis yielded an area under the curve of 0.84 (95% CI: 0.73\u20130.95). At a data-derived optimal cutoff of 42% (Youden index), sensitivity was 83%, specificity 85%, positive predictive value 80.0%, negative predictive value 87.2%, and overall diagnostic accuracy 84.0%. Histopathological Prussian Blue grading supported differential iron uptake patterns between groups. High VEGF-C expression (\u2265++) was more prevalent in metastatic than hyperplastic nodes (85.1% vs. 12.3%;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). PSIL showed a moderate inverse correlation with VEGF-C grade (Spearman\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.67;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SPIO-enhanced MRI demonstrated favorable diagnostic performance for differentiating metastatic from reactive hyperplastic lymph nodes at the patient level. The imaging characteristics were associated with supportive histopathological findings and VEGF-C expression patterns. These findings warrant validation in larger, multicenter studies using currently available iron oxide agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1800084","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:36:00Z","timestamp":1776832560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SPIO-enhanced MRI for differentiating metastatic from reactive hyperplastic lymph nodes in breast cancer: diagnostic performance and association with VEGF-C expression"],"prefix":"10.3389","volume":"13","author":[{"given":"Tao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Queen\u2019s University","place":["Kingston, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[{"name":"School of Medical Imaging, Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaying","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The First Affiliated Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhewen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanchang People\u2019s Hospital","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Luo","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Xiajiang County People\u2019s Hospital","place":["Xiajiang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medical Imaging, Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nrc1670","article-title":"Breast cancer metastasis: markers 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