{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T23:03:26Z","timestamp":1648595006387},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Res"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Recently, we reported an information density theory and an analysis of three-parameter plus shorter scan than conventional method (3P+) for the amyloid-binding ligand [<jats:sup>11<\/jats:sup>C]Pittsburgh compound B (PIB) as an example of a non-highly reversible positron emission tomography (PET) ligand. This article describes an extension of 3P\u2009+\u2009analysis to noninvasive \u20183P++\u2019 analysis (3P\u2009+\u2009plus use of a reference tissue for input function).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In 3P++ analysis for [<jats:sup>11<\/jats:sup>C]PIB, the cerebellum was used as a reference tissue (negligible specific binding). Fifteen healthy subjects (NC) and fifteen Alzheimer's disease (AD) patients participated. The <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> (index of receptor density) values were estimated with 40-min PET data and three-parameter reference tissue model and were compared with that in 40-min 3P\u2009+\u2009analysis as well as standard 90-min four-parameter (4P) analysis with arterial input function. Simulation studies were performed to explain <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> biases observed in 3P++ analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Good model fits of 40-min PET data were observed in both reference and target regions-of-interest (ROIs). High linear intra-subject (inter-15 ROI) correlations of <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> between 3P++ (<jats:italic>Y<\/jats:italic>-axis) and 3P\u2009+\u2009(<jats:italic>X<\/jats:italic>-axis) analyses were shown in one NC (<jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.972 and slope\u2009=\u20090.845) and in one AD (<jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.982, slope\u2009=\u20090.655), whereas inter-subject <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> correlations in a target region (left lateral temporal cortex) from 30 subjects (15 NC\u2009+\u200915 AD) were somewhat lower (<jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.739 and slope\u2009=\u20090.461). Similar results were shown between 3P++ and 4P analyses: <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.953 for intra-subject <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> in NC, <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.907 for that in AD and <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\u2009=\u20090.711 for inter-30 subject <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub>. Simulation studies showed that such lower inter-subject <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> correlations and significant negative <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> biases were not due to unstableness of 3P++ analysis but rather to inter-subject variation of both <jats:italic>k<\/jats:italic>\n              <jats:sub>2<\/jats:sub> (index of brain-to-blood transport) and <jats:italic>k<\/jats:italic>\n              <jats:sub>3<\/jats:sub> (not completely negligible) in the reference region.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In [<jats:sup>11<\/jats:sup>C]PIB, the applicability of 3P++ analysis may be restricted to intra-subject comparison such as follow-up studies. The 3P++ method itself is thought to be robust and may be more applicable to other non-highly reversible PET ligands with ideal reference tissue.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/2191-219x-3-76","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T08:01:27Z","timestamp":1384588887000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B"],"prefix":"10.1186","volume":"3","author":[{"given":"Koichi","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Fukushi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Shinotoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Suhara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Irie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,11,16]]},"reference":[{"key":"175_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/ana.410150302","volume":"15","author":"MA Mintun","year":"1984","unstructured":"Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ: A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. 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