{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:19:26Z","timestamp":1776745166156,"version":"3.51.2"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0A8517N"],"award-info":[{"award-number":["G0A8517N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1229721N"],"award-info":[{"award-number":["1229721N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Phys"],"abstract":"Abstract<\/jats:title>\n Background<\/jats:title>\n Kinetic modeling in positron emission tomography (PET) requires measurement of the tracer plasma activity in the absence of a suitable reference region. To avoid invasive blood sampling, the use of an image derived input function has been proposed. However, an accurate delineation of the blood pool region in the PET image is necessary to obtain unbiased blood activity. Here, to perform brain kinetic modeling in [18<\/jats:sup>F]SynVesT-1 dynamic scans, we make use of non-negative matrix factorization (NMF) to unmix the activity signal from the different tissues that can contribute to the heart region activity, and extract only the left ventricle activity in an unbiased way. This method was implemented in dynamic [18<\/jats:sup>F]SynVesT-1 scans of mice anesthetized with either isoflurane or ketamine\u2013xylazine, two anesthestics that we showed to affect differently radiotracer kinetics. The left ventricle activity (NMF-IDIF) and a manually delineated cardiac activity (IDIF) were compared with arterial blood samples (ABS), and for isoflurane anesthetized mice, arteriovenous (AV) shunt blood data were compared as well. Finally, brain regional 2 tissue compartment modeling was performed using IDIF and NMF-IDIF, and the model fit accuracy (weighted symmetrical mean absolute percentage error, wsMAPE) as well as the total volume of distribution (V<\/jats:italic>T<\/jats:sub>) were compared.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n In isoflurane anesthetized mice, the difference between ABS and NMF-IDIF activity (+\u200912.8 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 11%, p\u2009=\u20090.0023) was smaller than with IDIF (+\u200916.4 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 9.8%, p<\/jats:italic>\u2009=\u20090.0008). For ketamine\u2013xylazine anesthetized mice the reduction in difference was larger (NMF-IDIF: 16.9 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 10%, p<\/jats:italic>\u2009=\u20090.0057, IDIF: 56.3 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 14%, p<\/jats:italic>\u2009<\u20090.0001). Correlation coefficient between isoflurane AV-shunt time activity curves and NMF-IDIF (0.97 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.01) was higher than with IDIF (0.94 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.03). The brain regional 2TCM wsMAPE was improved using NMF-IDIF compared with IDIF, in isoflurane (NMF-IDIF: 1.24 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.24%, IDIF: 1.56 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.30%) and ketamine\u2013xylazine (NMF-IDIF: 1.40 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.24, IDIF: 2.62 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.27) anesthetized mice. Finally, brain V<\/jats:italic>T<\/jats:sub> was significantly (p<\/jats:italic>\u2009<\u20090.0001) higher using NMF-IDIF compared with IDIF, in isoflurane (3.97 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 0.13% higher) and ketamine\u2013xylazine (32.7 $$\\pm$$<\/jats:tex-math>\n \u00b1<\/mml:mo>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> 2.4% higher) anesthetized mice.<\/jats:p>\n <\/jats:sec>\n Conclusions<\/jats:title>\n Image derived left ventricle blood activity calculated with NMF improves absolute activity quantification, and reduces the error in the kinetic modeling fit. These improvements are more pronounced in ketamine\u2013xylazine than in isoflurane anesthetized mice.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s40658-023-00599-8","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T04:18:59Z","timestamp":1701836339000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accurate image derived input function in [18F]SynVesT-1 mouse studies using isoflurane and ketamine\/xylazine anesthesia"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-015X","authenticated-orcid":false,"given":"Alan","family":"Miranda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Bertoglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Staelens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"Verhaeghe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"599_CR1","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1038\/sj.jcbfm.9600493","volume":"27","author":"RB Innis","year":"2007","unstructured":"Innis RB, Cunningham VJ, Delforge J, et al. 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EJNMMI Res. 2011;1:13.","journal-title":"EJNMMI Res"}],"container-title":["EJNMMI Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40658-023-00599-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40658-023-00599-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40658-023-00599-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T04:22:18Z","timestamp":1701836538000},"score":1,"resource":{"primary":{"URL":"https:\/\/ejnmmiphys.springeropen.com\/articles\/10.1186\/s40658-023-00599-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["599"],"URL":"https:\/\/doi.org\/10.1186\/s40658-023-00599-8","relation":{},"ISSN":["2197-7364"],"issn-type":[{"value":"2197-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]},"assertion":[{"value":"24 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experiments followed the European Ethics Committee recommendations (Decree 2010\/63\/CEE) and were approved by the Animal Experimental Ethical Committee of the University of Antwerp, Antwerp, Belgium (ECD 2020\u201359, 2020\u201371 and 2022\u201339).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}