{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:21:29Z","timestamp":1790688089169,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EK1605A HitTau"],"award-info":[{"award-number":["01EK1605A HitTau"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2145 SyNergy \u2013 ID 390857198)"],"award-info":[{"award-number":["EXC 2145 SyNergy \u2013 ID 390857198)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinik M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>[<jats:sup>18<\/jats:sup>F]PI-2620 positron emission tomography (PET) detects misfolded tau in progressive supranuclear palsy (PSP) and Alzheimer\u2019s disease (AD). We questioned the feasibility and value of absolute [<jats:sup>18<\/jats:sup>F]PI-2620 PET quantification for assessing tau by regional distribution volumes (V<jats:sub>T<\/jats:sub>). Here, arterial input functions (AIF) represent the gold standard, but cannot be applied in routine clinical practice, whereas image-derived input functions (IDIF) represent a non-invasive alternative. We aimed to validate IDIF against AIF and we evaluated the potential to discriminate patients with PSP and AD from healthy controls by non-invasive quantification of [<jats:sup>18<\/jats:sup>F] PET.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the first part of the study, we validated AIF derived from radial artery whole blood against IDIF by investigating 20 subjects (ten controls and ten patients). IDIF were generated by manual extraction of the carotid artery using the average and the five highest (max5) voxel intensity values and by automated extraction of the carotid artery using the average and the maximum voxel intensity value. In the second part of the study, IDIF quantification using the IDIF with the closest match to the AIF was transferred to group comparison of a large independent cohort of 40 subjects (15 healthy controls, 15 PSP patients and 10 AD patients). We compared V<jats:sub>T<\/jats:sub> and V<jats:sub>T<\/jats:sub> ratios, both calculated by Logan plots, with distribution volume (DV) ratios using simplified reference tissue modelling and standardized uptake value (SUV) ratios.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>AIF and IDIF showed highly correlated input curves for all applied IDIF extraction methods (0.78\u2009&lt;\u2009r\u2009&lt;\u20090.83, all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001; area under the curves (AUC): 0.73\u2009&lt;\u2009r\u2009\u2264\u20090.82, all <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0003). Regarding the V<jats:sub>T<\/jats:sub> values, correlations were mainly found between those generated by the AIF and by the IDIF methods using the maximum voxel intensity values. Lowest relative differences (RD) were observed by applying the manual method using the five highest voxel intensity values (max5) (AIF vs. IDIF manual, avg: RD\u2009=\u2009-82%; AIF vs. IDIF automated, avg: RD\u2009=\u2009-86%; AIF vs. IDIF manual, max5: RD\u2009=\u2009-6%; AIF vs. IDIF automated, max: RD\u2009=\u2009-26%). Regional V<jats:sub>T<\/jats:sub> values revealed considerable variance at group level, which was strongly reduced upon scaling by the inferior cerebellum. The resulting V<jats:sub>T<\/jats:sub> ratio values were adequate to detect group differences between patients with PSP or AD and healthy controls (HC) (PSP target region (globus pallidus): HC vs. PSP vs. AD: 1.18 vs. 1.32 vs. 1.16; AD target region (Braak region I): HC vs. PSP vs. AD: 1.00 vs. 1.00 vs. 1.22). V<jats:sub>T<\/jats:sub> ratios and DV ratios outperformed SUV ratios and V<jats:sub>T<\/jats:sub> in detecting differences between PSP and healthy controls, whereas all quantification approaches performed similarly in comparing AD and healthy controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Blood-free IDIF is a promising approach for quantification of [<jats:sup>18<\/jats:sup>F]PI-2620 PET, serving as correlating surrogate for invasive continuous arterial blood sampling. Regional [<jats:sup>18<\/jats:sup>F]PI-2620 V<jats:sub>T<\/jats:sub> show large variance, in contrast to regional [<jats:sup>18<\/jats:sup>F]PI-2620 V<jats:sub>T<\/jats:sub> ratios scaled with the inferior cerebellum, which are appropriate for discriminating PSP, AD and healthy controls. DV ratios obtained by simplified reference tissue modeling are similarly suitable for this purpose.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-024-06741-7","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T08:01:51Z","timestamp":1715155311000},"page":"3252-3266","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Assessment of [18F]PI-2620 Tau-PET Quantification via Non-Invasive Automatized Image Derived Input Function"],"prefix":"10.1007","volume":"51","author":[{"given":"Maria","family":"Meindl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Zatcepin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gn\u00f6rich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Scheifele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirlind","family":"Zaganjori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattes","family":"Gro\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Simmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Roemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Katzdobler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"H\u00f6glinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Cathrin","family":"Bischof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryk","family":"Barthel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Sabri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bartenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Saller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"6741_CR1","doi-asserted-by":"publisher","first-page":"911","DOI":"10.2967\/jnumed.119.236224","volume":"61","author":"A Mueller","year":"2020","unstructured":"Mueller A, Bullich S, Barret O, et al. Tau PET imaging with 18F-PI-2620 in patients with Alzheimer disease and healthy controls: a first-in-humans study. J Nucl Med. 2020;61:911\u20139.","journal-title":"J Nucl Med"},{"key":"6741_CR2","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1001\/jamaneurol.2020.2526","volume":"77","author":"M Brendel","year":"2020","unstructured":"Brendel M, Barthel H, van Eimeren T, et al. Assessment of 18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol. 2020;77:1408\u201319.","journal-title":"JAMA Neurol"},{"key":"6741_CR3","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1002\/mds.28624","volume":"36","author":"C Palleis","year":"2021","unstructured":"Palleis C, Brendel M, Finze A, et al. Cortical [18F] PI-2620 Binding Differentiates Corticobasal Syndrome Subtypes. Mov Disord. 2021;36:2104\u201315.","journal-title":"Mov Disord"},{"key":"6741_CR4","doi-asserted-by":"publisher","first-page":"3872","DOI":"10.1007\/s00259-021-05391-3","volume":"48","author":"M Song","year":"2021","unstructured":"Song M, Scheifele M, Barthel H, et al. Feasibility of short imaging protocols for [18 F] PI-2620 tau-PET in progressive supranuclear palsy. Eur J Nucl Med Mol Imaging. 2021;48:3872\u201385.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"6741_CR5","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1177\/0271678X211018904","volume":"41","author":"M Song","year":"2021","unstructured":"Song M, Beyer L, Kaiser L, et al. Binding characteristics of [18F] PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. J Cereb Blood Flow Metab. 2021;41:2957\u201372.","journal-title":"J Cereb Blood Flow Metab"},{"key":"6741_CR6","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1021\/acschemneuro.2c00291","volume":"13","author":"G K\u00fcnze","year":"2022","unstructured":"K\u00fcnze G, K\u00fcmpfel R, Rullmann M, et al. Molecular Simulations Reveal Distinct Energetic and Kinetic Binding Properties of [18F] PI-2620 on Tau Filaments from 3R\/4R and 4R Tauopathies. ACS Chem Neurosci. 2022;13:2222\u201334.","journal-title":"ACS Chem Neurosci"},{"key":"6741_CR7","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1038\/s41467-022-28896-3","volume":"13","author":"N Franzmeier","year":"2022","unstructured":"Franzmeier N, Brendel M, Beyer L, et al. Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Commun. 2022;13:1362.","journal-title":"Nat Commun"},{"key":"6741_CR8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00401-020-02158-2","volume":"140","author":"GG Kovacs","year":"2020","unstructured":"Kovacs GG, Lukic MJ, Irwin DJ, et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol. 2020;140:99\u2013119.","journal-title":"Acta Neuropathol"},{"key":"6741_CR9","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.26987","volume":"32","author":"GU H\u00f6glinger","year":"2017","unstructured":"H\u00f6glinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853\u201364.","journal-title":"Mov Disord"},{"key":"6741_CR10","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:535\u201362.","journal-title":"Alzheimers Dement"},{"key":"6741_CR11","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S1474-4422(20)30314-8","volume":"19","author":"G Ch\u00e9telat","year":"2020","unstructured":"Ch\u00e9telat G, Arbizu J, Barthel H, et al. Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer\u2019s disease and other dementias. Lancet Neurol. 2020;19:951\u201362.","journal-title":"Lancet Neurol"},{"key":"6741_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/WAD.0000000000000144","volume":"30","author":"J Sevigny","year":"2016","unstructured":"Sevigny J, Suhy J, Chiao P, et al. Amyloid PET screening for enrichment of early-stage Alzheimer disease clinical trials. Alzheimer Dis Assoc Disorders. 2016;30:1\u20137.","journal-title":"Alzheimer Dis Assoc Disorders"},{"key":"6741_CR13","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1007\/s00259-022-06087-y","volume":"50","author":"F V\u00f6lter","year":"2023","unstructured":"V\u00f6lter F, Beyer L, Eckenweber F, et al. Assessment of perfusion deficit with early phases of [18F] PI-2620 tau-PET versus [18F] flutemetamol-amyloid-PET recordings. Eur J Nuclear Med Molec Imaging. 2023;50:1384\u201394.","journal-title":"Eur J Nuclear Med Molec Imaging"},{"key":"6741_CR14","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.nicl.2016.10.005","volume":"14","author":"S Daerr","year":"2017","unstructured":"Daerr S, Brendel M, Zach C, et al. Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases. NeuroImage: Clinical. 2017;14:77\u201386.","journal-title":"NeuroImage: Clinical"},{"key":"6741_CR15","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1097\/MNM.0b013e328356185c","volume":"33","author":"P Zanotti-Fregonara","year":"2012","unstructured":"Zanotti-Fregonara P, Liow J-S, Comtat C, et al. Image-derived input function in PET brain studies: blood-based methods are resistant to motion artifacts. Nucl Med Commun. 2012;33:982\u20139.","journal-title":"Nucl Med Commun"},{"key":"6741_CR16","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1177\/0271678X21991393","volume":"41","author":"S Kuttner","year":"2021","unstructured":"Kuttner S, Wickstr\u00f8m KK, Lubberink M, et al. Cerebral blood flow measurements with 15O-water PET using a non-invasive machine-learning-derived arterial input function. J Cereb Blood Flow Metab. 2021;41:2229\u201341.","journal-title":"J Cereb Blood Flow Metab"},{"key":"6741_CR17","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3233\/ADR-170023","volume":"1","author":"M Brendel","year":"2017","unstructured":"Brendel M, Wagner L, Levin J, et al. Perfusion-phase [18F] THK5351 Tau-PET imaging as a surrogate marker for neurodegeneration. J Alzheimer\u2019s Dis Reports. 2017;1:109\u201313.","journal-title":"J Alzheimer's Dis Reports"},{"key":"6741_CR18","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/jcbfm.1990.127","volume":"10","author":"J Logan","year":"1990","unstructured":"Logan J, Fowler JS, Volkow ND, et al. Graphical analysis of reversible radioligand binding from time\u2014activity measurements applied to [N-11C-methyl]-(\u2212)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. 1990;10:740\u20137.","journal-title":"J Cereb Blood Flow Metab"},{"key":"6741_CR19","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1007\/s00429-016-1352-4","volume":"222","author":"M Keuken","year":"2017","unstructured":"Keuken M, Bazin P-L, Backhouse K, et al. Effects of aging on T_ 1 T 1, T_ 2^* T 2\u2217, and QSM MRI values in the subcortex. Brain Struct Funct. 2017;222:2487\u2013505.","journal-title":"Brain Struct Funct"},{"key":"6741_CR20","doi-asserted-by":"publisher","first-page":"3508","DOI":"10.1093\/cercor\/bhw157","volume":"26","author":"L Fan","year":"2016","unstructured":"Fan L, Li H, Zhuo J, et al. The human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex. 2016;26:3508\u201326.","journal-title":"Cereb Cortex"},{"key":"6741_CR21","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/hbm.10123","volume":"19","author":"A Hammers","year":"2003","unstructured":"Hammers A, Allom R, Koepp MJ, et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003;19:224\u201347.","journal-title":"Hum Brain Mapp"},{"key":"6741_CR22","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1093\/brain\/awm104","volume":"130","author":"DR Williams","year":"2007","unstructured":"Williams DR, Holton JL, Strand C, et al. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson\u2019s syndrome. Brain. 2007;130:1566\u201376.","journal-title":"Brain"},{"key":"6741_CR23","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s12021-018-9384-y","volume":"17","author":"FJ L\u00f3pez-Gonz\u00e1lez","year":"2019","unstructured":"L\u00f3pez-Gonz\u00e1lez FJ, Paredes-Pacheco J, Thurnhofer-Hemsi K, et al. QModeling: a multiplatform, easy-to-use and open-source toolbox for PET kinetic analysis. Neuroinformatics. 2019;17:103\u201314.","journal-title":"Neuroinformatics"},{"key":"6741_CR24","doi-asserted-by":"publisher","first-page":"458","DOI":"10.3390\/biom12030458","volume":"12","author":"M Rullmann","year":"2022","unstructured":"Rullmann M, Brendel M, Schroeter ML, et al. Multicenter 18F-PI-2620 PET for in vivo Braak staging of tau pathology in Alzheimer\u2019s disease. Biomolecules. 2022;12:458.","journal-title":"Biomolecules"},{"key":"6741_CR25","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1177\/0271678X16656197","volume":"37","author":"H Sari","year":"2017","unstructured":"Sari H, Erlandsson K, Law I, et al. Estimation of an image derived input function with MR-defined carotid arteries in FDG-PET human studies using a novel partial volume correction method. J Cereb Blood Flow Metab. 2017;37:1398\u2013409.","journal-title":"J Cereb Blood Flow Metab"},{"key":"6741_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118194","volume":"237","author":"M Galovic","year":"2021","unstructured":"Galovic M, Erlandsson K, Fryer TD, et al. Validation of a combined image derived input function and venous sampling approach for the quantification of [18F] GE-179 PET binding in the brain. Neuroimage. 2021;237: 118194.","journal-title":"Neuroimage"},{"key":"6741_CR27","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.neuroimage.2007.10.022","volume":"39","author":"JE Mourik","year":"2008","unstructured":"Mourik JE, Lubberink M, Klumpers UM, et al. Partial volume corrected image derived input functions for dynamic PET brain studies: methodology and validation for [11C] flumazenil. Neuroimage. 2008;39:1041\u201350.","journal-title":"Neuroimage"},{"key":"6741_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13024-017-0162-3","volume":"12","author":"L Saint-Aubert","year":"2017","unstructured":"Saint-Aubert L, Lemoine L, Chiotis K, et al. Tau PET imaging: present and future directions. Mol Neurodegener. 2017;12:1\u201321.","journal-title":"Mol Neurodegener"},{"key":"6741_CR29","doi-asserted-by":"publisher","first-page":"920","DOI":"10.2967\/jnumed.119.236240","volume":"61","author":"S Bullich","year":"2020","unstructured":"Bullich S, Barret O, Constantinescu C, et al. Evaluation of dosimetry, quantitative methods, and test\u2013retest variability of 18F-PI-2620 PET for the assessment of tau deposits in the human brain. J Nucl Med. 2020;61:920\u20137.","journal-title":"J Nucl Med"},{"key":"6741_CR30","doi-asserted-by":"publisher","first-page":"20","DOI":"10.14802\/jmd.19061","volume":"13","author":"S Ando","year":"2020","unstructured":"Ando S, Kanazawa M, Onodera OJJoMD. Progressive supranuclear palsy with predominant cerebellar ataxia. J Movement Disorders. 2020;13:20.","journal-title":"J Movement Disorders"},{"key":"6741_CR31","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1111\/j.1750-3639.2010.00469.x","volume":"21","author":"D Sepulveda-Falla","year":"2011","unstructured":"Sepulveda-Falla D, Matschke J, Bernreuther C, et al. Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer\u2019s disease. Brain Pathol. 2011;21:452\u201363.","journal-title":"Brain Pathol"},{"key":"6741_CR32","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.2967\/jnumed.112.113654","volume":"54","author":"BN van Berckel","year":"2013","unstructured":"van Berckel BN, Ossenkoppele R, Tolboom N, et al. Longitudinal amyloid imaging using 11C-PiB: methodologic considerations. J Nucl Med. 2013;54:1570\u20136.","journal-title":"J Nucl Med"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-024-06741-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-024-06741-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-024-06741-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T18:02:36Z","timestamp":1725300156000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-024-06741-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["6741"],"URL":"https:\/\/doi.org\/10.1007\/s00259-024-06741-7","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]},"assertion":[{"value":"15 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"G.H. received research support from GE Healthcare and Neuropore; has ongoing research collaborations with Orion and Prothena; serves as a consultant for AbbVie, AlzProtect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Roche, Sanofi, UCB; received honoraria for scientific presentations from AbbVie, Biogen, Roche, Teva, UCB, and Zambon; and holds a patent on PERK Activation for the Treatment of Neurodegenerative Diseases (PCT\/EP2015\/068734). O.S. receives research support from LMI. M.B. received speaker honoraria from GE healthcare and LMI and is an advisor of LMI. All other authors do not report a conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the LMU Munich (approval IDs 21\u20130170, 17\u2013569 and 19\u2013022).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images in Figure(s) , ,  and .","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}