{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:15:56Z","timestamp":1790820956152,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>This technical note seeks to act as a practical guide for implementing a supervised\u00a0clustering algorithm (SVCA) reference region approach and to explain the main strengths\u00a0and limitations of the technique in the context of 18-kilodalton translocator protein (TSPO)\u00a0positron emission tomography (PET) studies in experimental medicine.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>TSPO PET is the most widely used imaging technique for studying neuroinflammation in\u00a0vivo in humans. Quantifying neuroinflammation with PET can be a challenging and invasive\u00a0procedure, especially in frail patients, because it often requires blood sampling from an\u00a0arterial catheter. A widely used alternative to arterial sampling is SVCA, which identifies the\u00a0voxels with minimal specific binding in the PET images, thus extracting a pseudo-reference\u00a0region for non-invasive quantification. Unlike other reference region approaches, SVCA does\u00a0not require specification of an anatomical reference region a priori, which alleviates the\u00a0limitation of TSPO contamination in anatomically-defined reference regions in individuals\u00a0with underlying inflammatory processes. Furthermore, SVCA can be applied to any TSPO\u00a0PET tracer across different neurological and neuropsychiatric conditions, providing noninvasivequantification of TSPO expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We provide an overview of the development of SVCA as well as step-by-step instructions for\u00a0implementing SVCA with suggestions for specific settings. We review the literature on SVCAapplications using first- and second- generation TSPO PET tracers and discuss potential\u00a0clinically relevant limitations and applications.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The correct implementation of SVCA can provide robust and reproducible estimates of brain\u00a0TSPO expression. This review encourages the standardisation of SVCA methodology in\u00a0TSPO PET analysis, ultimately aiming to improve replicability and comparability across\u00a0study sites.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-021-05309-z","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T08:02:24Z","timestamp":1617004944000},"page":"257-268","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Supervised clustering for TSPO PET imaging"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-7272","authenticated-orcid":false,"given":"Julia","family":"Schubert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Tonietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Turkheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Zanotti-Fregonara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-0683","authenticated-orcid":false,"given":"Mattia","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"5309_CR1","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1038\/jcbfm.2011.107","volume":"31","author":"P Zanotti-Fregonara","year":"2011","unstructured":"Zanotti-Fregonara P, Chen K, Liow JS, Fujita M, Innis RB. Image-derived input function for brain PET studies: many challenges and few opportunities. J Cereb Blood Flow Metab. 2011;31:1986\u201398. https:\/\/doi.org\/10.1038\/jcbfm.2011.107.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR2","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.neuroimage.2012.08.007","volume":"63","author":"P Zanotti-fregonara","year":"2012","unstructured":"Zanotti-fregonara P, Hines CS, Zoghbi SS, Liow J, Zhang Y, Pike VW, et al. Population-based input function and image-derived input function for [11C](R)-rolipram PET imaging: methodology, validation and application to the study of major depressive disorder. Neuroimage. 2012;63:1532\u201341.","journal-title":"Neuroimage."},{"key":"5309_CR3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/BF02984467","volume":"18","author":"S Takagi","year":"2004","unstructured":"Takagi S, Takahashi W, Shinohara Y, Yasuda S, Ide M, Shohtsu A, et al. Quantitative PET cerebral glucose metabolism estimates using a single non-arterialized venous-blood sample. Ann Nucl Med. 2004;18:297\u2013302.","journal-title":"Ann Nucl Med"},{"key":"5309_CR4","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1177\/0271678X18771242","volume":"39","author":"G Tomasi","year":"2019","unstructured":"Tomasi G, Veronese M, Bertoldo A, Smith CB, Schmidt KC. Substitution of venous for arterial blood sampling in the determination of regional rates of cerebral protein synthesis with L-[1-11C]leucine PET: a validation study. J Cereb Blood Flow Metab. 2019;39:1849\u201363.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR5","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/jcbfm.2009.245","volume":"30","author":"RT Ogden","year":"2010","unstructured":"Ogden RT, Zanderigo F, Choy S, Mann JJ, Parsey RV. Simultaneous estimation of input functions: an empirical study. J Cereb Blood Flow Metab. 2010;30:816\u201326. https:\/\/doi.org\/10.1038\/jcbfm.2009.245.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR6","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.neuroimage.2018.11.020","volume":"188","author":"P Plav\u00e9n-Sigray","year":"2019","unstructured":"Plav\u00e9n-Sigray P, Schain M, Zanderigo F, Farde L, Halldin C, Forsberg A, et al. Accuracy and reliability of [ 11 C]PBR28 specific binding estimated without the use of a reference region. Neuroimage. 2019;188:102\u201310.","journal-title":"Neuroimage."},{"key":"5309_CR7","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1042\/BST20150058","volume":"43","author":"FE Turkheimer","year":"2015","unstructured":"Turkheimer FE, Rizzo G, Bloomfield PS, Howes O, Zanotti-Fregonara P, Bertoldo A, et al. The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans. 2015;43:586\u201392.","journal-title":"Biochem Soc Trans"},{"key":"5309_CR8","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0969-8051(02)00410-9","volume":"30","author":"A Lockhart","year":"2003","unstructured":"Lockhart A, Davis B, Matthews JC, Rahmoune H, Hong G, Gee A, et al. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant \u03b11-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. Nucl Med Biol. 2003;30:199\u2013206.","journal-title":"Nucl Med Biol"},{"key":"5309_CR9","doi-asserted-by":"publisher","first-page":"701","DOI":"10.2967\/jnumed.114.146027","volume":"56","author":"CH Lyoo","year":"2015","unstructured":"Lyoo CH, Ikawa M, Liow J-S, Zoghbi SS, Morse C, Pike VW, et al. Cerebellum can serve as a pseudo-reference region in Alzheimer\u2019s disease to detect neuroinflammation measured with PET radioligand binding to translocator protein (TSPO). J Nucl Med. 2015;56:701\u20136.","journal-title":"J Nucl Med"},{"key":"5309_CR10","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/brain\/awu377","volume":"138","author":"ML Loggia","year":"2015","unstructured":"Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, et al. Evidence for brain glial activation in chronic pain patients. Brain. 2015;138:604\u201315.","journal-title":"Brain"},{"key":"5309_CR11","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.nicl.2015.01.009","volume":"7","author":"NR Z\u00fcrcher","year":"2015","unstructured":"Z\u00fcrcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, et al. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [11C]-PBR28. NeuroImage Clin. 2015;7:409\u201314. https:\/\/doi.org\/10.1016\/j.nicl.2015.01.009.","journal-title":"NeuroImage Clin"},{"key":"5309_CR12","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.2967\/jnumed.113.135129","volume":"55","author":"A Colasanti","year":"2014","unstructured":"Colasanti A, Guo Q, Muhlert N, Giannetti P, Onega M, Newbould RD, et al. In vivo assessment of brain white matter inflammation in multiple sclerosis with 18F-PBR111 PET. J Nucl Med. 2014;55:1112\u20138.","journal-title":"J Nucl Med"},{"key":"5309_CR13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/jcbfm.2011.108","volume":"32","author":"FE Turkheimer","year":"2012","unstructured":"Turkheimer FE, Selvaraj S, Hinz R, Murthy V, Bhagwagar Z, Grasby P, et al. Quantification of ligand PET studies using a reference region with a displaceable fraction: application to occupancy studies with 11C-DASB as an example. J Cereb Blood Flow Metab. 2012;32:70\u201380.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR14","first-page":"158","volume":"48","author":"FE Turkheimer","year":"2007","unstructured":"Turkheimer FE, Edison P, Pavese N, Roncaroli F, Anderson AN, Hammers A, et al. Reference and target region modeling of [11C]-(R)-PK11195 brain studies. J Nucl Med. 2007;48:158\u201367.","journal-title":"J Nucl Med"},{"key":"5309_CR15","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1038\/jcbfm.2012.59","volume":"32","author":"M Yaqub","year":"2012","unstructured":"Yaqub M, Van Berckel BNM, Schuitemaker A, Hinz R, Turkheimer FE, Tomasi G, et al. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[ 11C]PK11195 brain PET studies. J Cereb Blood Flow Metab. 2012;32:1600\u20138.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR16","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.nbd.2008.08.001","volume":"32","author":"P Edison","year":"2008","unstructured":"Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer\u2019s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412\u20139. https:\/\/doi.org\/10.1016\/j.nbd.2008.08.001.","journal-title":"Neurobiol Dis"},{"key":"5309_CR17","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.neurobiolaging.2012.04.021","volume":"34","author":"A Schuitemaker","year":"2013","unstructured":"Schuitemaker A, Kropholler MA, Boellaard R, van der Flier WM, Kloet RW, van der Doef TF, et al. Microglial activation in Alzheimer\u2019s disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiol Aging. 2013;34:128\u201336. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.04.021.","journal-title":"Neurobiol Aging"},{"key":"5309_CR18","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/ana.22455","volume":"70","author":"AF Ramlackhansingh","year":"2011","unstructured":"Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol. 2011;70:374\u201383.","journal-title":"Ann Neurol"},{"key":"5309_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/npjschz.2016.31","volume":"2","author":"TF Van Der Doef","year":"2016","unstructured":"Van Der Doef TF, De Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, et al. In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. npj Schizophr. 2016;2:1\u20135. https:\/\/doi.org\/10.1038\/npjschz.2016.31.","journal-title":"npj Schizophr"},{"key":"5309_CR20","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1007\/s00259-013-2447-2","volume":"40","author":"Z Su","year":"2013","unstructured":"Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A, et al. [11C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging. 2013;40:1406\u201319.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"5309_CR21","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s40336-015-0138-7","volume":"3","author":"R Hinz","year":"2015","unstructured":"Hinz R, Boellaard R. Challenges of quantification of TSPO in the human brain. Clin Transl Imaging. 2015;3:403\u201316.","journal-title":"Clin Transl Imaging"},{"key":"5309_CR22","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1177\/0271678X17742004","volume":"39","author":"G Rizzo","year":"2019","unstructured":"Rizzo G, Veronese M, Tonietto M, Bodini B, Stankoff B, Wimberley C, et al. Generalization of endothelial modelling of TSPO PET imaging: considerations on tracer affinities. J Cereb Blood Flow Metab. 2019;39:874\u201385.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR23","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1177\/0271678X17692599","volume":"38","author":"D Garc\u00eda-Lorenzo","year":"2018","unstructured":"Garc\u00eda-Lorenzo D, Lavisse S, Leroy C, Wimberley C, Bodini B, Remy P, et al. Validation of an automatic reference region extraction for the quantification of [ 18 F]DPA-714 in dynamic brain PET studies. J Cereb Blood Flow Metab. 2018;38:333\u201346.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR24","doi-asserted-by":"publisher","first-page":"978","DOI":"10.2967\/jnumed.118.222927","volume":"60","author":"P Zanotti-Fregonara","year":"2019","unstructured":"Zanotti-Fregonara P, Kreisl WC, Innis RB, Lyoo CH. Automatic extraction of a reference region for the noninvasive quantification of translocator protein in brain using 11C-PBR28. J Nucl Med. 2019;60:978\u201384.","journal-title":"J Nucl Med"},{"key":"5309_CR25","doi-asserted-by":"publisher","first-page":"5897","DOI":"10.2174\/1381612820666140613120212","volume":"20","author":"D Ory","year":"2014","unstructured":"Ory D, Celen S, Verbruggen A, Bormans G. PET radioligands for in vivo visualization of neuroinflammation. Curr Pharm Des. 2014;20:5897\u2013913.","journal-title":"Curr Pharm Des"},{"key":"5309_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jcbfm.2011.147","volume":"32","author":"DR Owen","year":"2012","unstructured":"Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa Translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1\u20135. https:\/\/doi.org\/10.1038\/jcbfm.2011.147.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR27","doi-asserted-by":"crossref","unstructured":"Boellaard R, Turkheimer FE, Hinz R, Schuitemaker A, Scheltens P, van Berckel BNM, et al. Performance of a modified supervised cluster algorithm for extracting reference region input functions from (R)-[11C]PK11195 brain PET studies. 2008 IEEE Nucl Sci Symp Conf Rec. IEEE; 2008. p. 5400\u20132.","DOI":"10.1109\/NSSMIC.2008.4774453"},{"key":"5309_CR28","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.2967\/jnumed.115.156083","volume":"56","author":"S Lavisse","year":"2015","unstructured":"Lavisse S, Garc\u00eda-Lorenzo D, Peyronneau M-AM-AA, Bodini B, Thiriez C, Kuhnast B, et al. Optimized quantification of translocator protein radioligand 18F-DPA-714 uptake in the brain of genotyped healthy volunteers. J Nucl Med. 2015;56:1048\u201354.","journal-title":"J Nucl Med"},{"key":"5309_CR29","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1038\/jcbfm.2013.133","volume":"33","author":"Y Ikoma","year":"2013","unstructured":"Ikoma Y, Edison P, Ramlackhansingh A, Brooks DJ, Turkheimer FE. Reference region automatic extraction in dynamic [ 11 C]PIB. J Cereb Blood Flow Metab. 2013;33:1725\u201331.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR30","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/jcbfm.1995.17","volume":"15","author":"NA Lassen","year":"1995","unstructured":"Lassen NA, Bartenstein PA, Lammertsma AA, Prevett MC, Turton DR, Luthra SK, et al. Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle. J Cereb Blood Flow Metab. 1995;15:152\u201365.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR31","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1177\/0271678X17712388","volume":"38","author":"M Veronese","year":"2018","unstructured":"Veronese M, Reis Marques T, Bloomfield PS, Rizzo G, Singh N, Jones D, et al. Kinetic modelling of [ 11 C]PBR28 for 18 kDa translocator protein PET data: a validation study of vascular modelling in the brain using XBD173 and tissue analysis. J Cereb Blood Flow Metab. 2018;38:1227\u201342.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR32","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/jcbfm.2014.46","volume":"34","author":"DR Owen","year":"2014","unstructured":"Owen DR, Guo Q, Kalk NJ, Colasanti A, Kalogiannopoulou D, Dimber R, et al. Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study. J Cereb Blood Flow Metab. 2014;34:989\u201394.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR33","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1198\/000313001300339897","volume":"55","author":"JM Hoenig","year":"2001","unstructured":"Hoenig JM, Heisey DM. The abuse of power. Am Stat. 2001;55:19\u201324.","journal-title":"Am Stat"},{"key":"5309_CR34","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1093\/brain\/awu331","volume":"138","author":"P Giannetti","year":"2015","unstructured":"Giannetti P, Politis M, Su P, Turkheimer FE, Malik O, Keihaninejad S, et al. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain. 2015;138:110\u20139.","journal-title":"Brain."},{"key":"5309_CR35","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.neurobiolaging.2010.09.016","volume":"33","author":"A Schuitemaker","year":"2012","unstructured":"Schuitemaker A, van der Doef TF, Boellaard R, van der Flier WM, Yaqub M, Windhorst AD, et al. Microglial activation in healthy aging. Neurobiol Aging. 2012;33:1067\u201372. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2010.09.016.","journal-title":"Neurobiol Aging"},{"key":"5309_CR36","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, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533\u20139.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR37","doi-asserted-by":"publisher","first-page":"3819","DOI":"10.1088\/0031-9155\/48\/23\/002","volume":"48","author":"FE Turkheimer","year":"2003","unstructured":"Turkheimer FE, Hinz R, Gunn RN, Aston JAD, Gunn SR, Cunningham VJ. Rank-shaping regularization of exponential spectral analysis for application to functional parametric mapping. Phys Med Biol. 2003;48:3819\u201341.","journal-title":"Phys Med Biol"},{"key":"5309_CR38","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s13550-018-0455-8","volume":"8","author":"P Plav\u00e9n-Sigray","year":"2018","unstructured":"Plav\u00e9n-Sigray P, Matheson GJ, Csel\u00e9nyi Z, Jucaite A, Farde L, Cervenka S. Test-retest reliability and convergent validity of (R)-[11C]PK11195 outcome measures without arterial input function. EJNMMI Res. 2018;8:102.","journal-title":"EJNMMI Res"},{"key":"5309_CR39","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.2967\/jnumed.119.231340","volume":"61","author":"B Bodini","year":"2020","unstructured":"Bodini B, Poirion E, Tonietto M, Benoit C, Palladino R, Maillart E, et al. Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of worsening disability in multiple sclerosis. J Nucl Med. 2020;61:1043\u20139.","journal-title":"J Nucl Med"},{"key":"5309_CR40","first-page":"289","volume":"58","author":"S Love","year":"2017","unstructured":"Love S, Jaouen V, Annan M, Cottier J-P, Vercouillie J, Guilloteau D, et al. Robust supervised clustering analysis of 18F DPA-714 dynamic clinical PET data. J Nucl Med. 2017;58:289.","journal-title":"J Nucl Med"},{"key":"5309_CR41","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1177\/0271678X19859034","volume":"40","author":"N Van Camp","year":"2020","unstructured":"Van Camp N, Balbastre Y, Herard A-S, Lavisse S, Tauber C, Wimberley C, et al. Assessment of simplified methods for quantification of [ 18 F]-DPA-714 using 3D whole-brain TSPO immunohistochemistry in a non-human primate. J Cereb Blood Flow Metab. 2020;40:1103\u201316.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR42","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13550-018-0467-4","volume":"8","author":"IF Vieira","year":"2018","unstructured":"Vieira IF, Ory D, Casteels C, Lima FRA, Van Laere K, Bormans G, et al. Volume-of-interest-based supervised cluster analysis for pseudo-reference region selection in [18F]DPA-714 PET imaging of the rat brain. EJNMMI Res. 2018;8:112.","journal-title":"EJNMMI Res"},{"key":"5309_CR43","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1177\/0271678X15610585","volume":"36","author":"M Tonietto","year":"2016","unstructured":"Tonietto M, Rizzo G, Veronese M, Fujita M, Zoghbi SS, Zanotti-Fregonara P, et al. Plasma radiometabolite correction in dynamic PET studies: insights on the available modeling approaches. J Cereb Blood Flow Metab. 2016;36:326\u201339.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR44","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1038\/jcbfm.2014.55","volume":"34","author":"G Rizzo","year":"2014","unstructured":"Rizzo G, Veronese M, Tonietto M, Zanotti-Fregonara P, Turkheimer FE, Bertoldo A. Kinetic modeling without accounting for the vascular component impairs the quantification of [11C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014;34:1060\u20139.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR45","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s40336-015-0141-z","volume":"3","author":"DR Owen","year":"2015","unstructured":"Owen DR, Guo Q, Rabiner EA, Gunn RN. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clin Transl Imaging. 2015;3:417\u201322.","journal-title":"Clin Transl Imaging"},{"key":"5309_CR46","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1088\/0031-9155\/55\/3\/010","volume":"55","author":"KR Gray","year":"2010","unstructured":"Gray KR, Contractor KB, Kenny LM, Al-Nahhas A, Shousha S, Stebbing J, et al. Kinetic filtering of [18F]fluorothymidine in positron emission tomography studies. Phys Med Biol. 2010;55:695\u2013709.","journal-title":"Phys Med Biol"},{"key":"5309_CR47","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1038\/jcbfm.2015.120","volume":"35","author":"M Veronese","year":"2015","unstructured":"Veronese M, Bodini B, Garc\u00eda-Lorenzo D, Battaglini M, Bongarzone S, Comtat C, et al. Quantification of [11C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography. J Cereb Blood Flow Metab. 2015;35:1771\u201382.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR48","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/jcbfm.2014.202","volume":"35","author":"CA Salinas","year":"2015","unstructured":"Salinas CA, Searle GE, Gunn RN. The simplified reference tissue model: model assumption violations and their impact on binding potential. J Cereb Blood Flow Metab. 2015;35:304\u201311.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5309_CR49","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2967\/jnumed.116.178335","volume":"59","author":"DS Albrecht","year":"2018","unstructured":"Albrecht DS, Normandin MD, Shcherbinin S, Wooten DW, Schwarz AJ, Z\u00fcrcher NR, et al. Pseudoreference regions for glial imaging with 11 C-PBR28: investigation in 2 clinical cohorts. J Nucl Med. 2018;59:107\u201314.","journal-title":"J Nucl Med"},{"key":"5309_CR50","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1002\/syn.20966","volume":"65","author":"RN Gunn","year":"2011","unstructured":"Gunn RN, Murthy V, Catafau AM, Searle G, Bullich S, Slifstein M, et al. Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1. Synapse. 2011;65:1319\u201332.","journal-title":"Synapse"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-021-05309-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-021-05309-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-021-05309-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T23:19:43Z","timestamp":1675120783000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-021-05309-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5309"],"URL":"https:\/\/doi.org\/10.1007\/s00259-021-05309-z","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]},"assertion":[{"value":"1 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"M. Veronese has received consulting honoraria from GSK. J. Schubert, M. Tonietto, F. Turkheimer and P. Zanotti-Fregonara declare that they have no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}]}}