{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:55:32Z","timestamp":1790931332979,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidad de Sevilla","id":[{"id":"https:\/\/ror.org\/03yxnpp24","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate whether semiquantitative striatal [\u00b9\u00b2\u00b3I]FP-CIT SPECT-derived metrics improve clinical differentiation of degenerative parkinsonism using an integrated machine learning approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross-sectional study included 487 patients with Parkinson\u2019s disease (PD) and 219 with atypical parkinsonisms (APS), classified as progressive supranuclear palsy (PSP,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009127), multiple system atrophy parkinsonian type (MSA-P,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200937), multiple system atrophy cerebellar type (MSA-C,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912), and corticobasal degeneration (CBD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200943). All participants underwent a [\u00b9\u00b2\u00b3I]FP-CIT SPECT. Striatal [\u00b9\u00b2\u00b3I]FP-CIT uptake was quantified using anatomical (caudate, putamen, ventral striatum) and functional (limbic, executive, sensorimotor) parcellations to calculate specific binding ratios, asymmetry indices, and inter-regional ratios. Discriminative performance of each metric was evaluated using receiver operating characteristic (ROC) curves analyses. A random forest classifier integrating all semiquantitative metrics was trained and validated, enabling data-driven identification diagnostic pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Caudate-to-putamen and sensorimotor-to-limbic inter-regional ratios showed the strongest discriminative performance (AUC up to 0.95) for differentiating PD from APS. The random forest achieved a 64% overall accuracy with high per-class specificities (&gt;\u200984%) and revealed two diagnostic pathways. A lower caudate-to-posterior putamen ratio, primarily grouped PSP, CBD and MSA-C, where lower contralateral sensorimotor uptake pointing to PSP while higher values and ipsilateral caudate uptake subregion further distinguishing CBD from MSA-C. A higher caudate-to-posterior putamen ratio, included PD and MSA-P, where lower ipsilateral caudate uptake together with a higher sensorimotor-to-cognitive ratio mainly differentiate both groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrating anatomical and functional [\u00b9\u00b2\u00b3I]FP-CIT SPECT metrics within a machine learning framework enhances the clinical differentiation of degenerative parkinsonisms and supports [\u00b9\u00b2\u00b3I]FP-CIT SPECT as a robust in vivo disease biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08022-x","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:32:59Z","timestamp":1783042379000},"page":"7391-7406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Semiquantitative [\u00b9\u00b2\u00b3I]FP-CIT SPECT metrics combined with machine learning improve clinical differentiation of Parkinson\u2019s disease and atypical parkinsonian syndrome"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8669-5389","authenticated-orcid":false,"given":"Paula","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-069X","authenticated-orcid":false,"given":"Pablo","family":"Franco-Rosado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6155-5585","authenticated-orcid":false,"given":"Patricia","family":"Diaz-Galvan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-1824","authenticated-orcid":false,"given":"Laura","family":"Mu\u00f1oz-Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0689-049X","authenticated-orcid":false,"given":"Antonio Cristobal","family":"Luque-Ambrosiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3576-1777","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Labrador-Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-0103","authenticated-orcid":false,"given":"Jes\u00fas","family":"Silva-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0054-7869","authenticated-orcid":false,"given":"Elena","family":"Ojeda-Lepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-1529","authenticated-orcid":false,"given":"Daniel","family":"Mac\u00edas-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-9289","authenticated-orcid":false,"given":"Astrid","family":"Adarmes-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-4628","authenticated-orcid":false,"given":"Silvia","family":"Jes\u00fas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Carrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-8250","authenticated-orcid":false,"given":"Jose Antonio","family":"Lojo-Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Garc\u00eda","family":"Solis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2600-9022","authenticated-orcid":false,"given":"Michel J.","family":"Grothe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-302X","authenticated-orcid":false,"given":"Pablo","family":"Mir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"issue":"7","key":"8022_CR1","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.amjmed.2019.03.001","volume":"132","author":"MT Hayes","year":"2019","unstructured":"Hayes MT. Parkinson\u2019s disease and parkinsonism. Am J Med. 2019;132(7):802\u20137. https:\/\/doi.org\/10.1016\/j.amjmed.2019.03.001.","journal-title":"Am J Med"},{"issue":"6","key":"8022_CR2","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1002\/mds.23713","volume":"26","author":"GK Wenning","year":"2011","unstructured":"Wenning GK, Litvan I, Tolosa E. Milestones in atypical and secondary parkinsonisms: atypical and secondary parkinsonism. Mov Disord. 2011;26(6):1083\u201395. https:\/\/doi.org\/10.1002\/mds.23713.","journal-title":"Mov Disord"},{"key":"8022_CR3","first-page":"155","volume":"165","author":"G Fabbrini","year":"2019","unstructured":"Fabbrini G, Fabbrini A, Suppa A. Progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration. Handbook of Clinical Neurology. Elsevier. 165;2019:pp. 155\u201377.","journal-title":"Elsevier"},{"issue":"9996","key":"8022_CR4","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","volume":"386","author":"LV Kalia","year":"2015","unstructured":"Kalia LV, Lang AE. Parkinson\u2019s disease. Lancet. 2015;386(9996):896\u2013912. https:\/\/doi.org\/10.1016\/S0140-6736(14)61393-3.","journal-title":"Lancet"},{"issue":"4 Movement Diso","key":"8022_CR5","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1212\/CON.0000000000000348","volume":"22","author":"NR McFarland","year":"2016","unstructured":"McFarland NR. Diagnostic approach to atypical parkinsonian syndromes. Continuum (Minneap Minn). 2016;22(4 Movement Disorders):1117\u201342. https:\/\/doi.org\/10.1212\/CON.0000000000000348.","journal-title":"Continuum (Minneap Minn)"},{"issue":"6","key":"8022_CR6","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1212\/WNL.0000000000002350","volume":"86","author":"G Rizzo","year":"2016","unstructured":"Rizzo G, Copetti M, Arcuti S, et al Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology. 2016;86(6):566\u201376. https:\/\/doi.org\/10.1212\/WNL.0000000000002350.","journal-title":"Neurology"},{"issue":"4","key":"8022_CR7","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1007\/s40120-024-00614-9","volume":"13","author":"EE Dunning","year":"2024","unstructured":"Dunning EE, Decourt B, Zawia NH, et al. Pharmacotherapies for the treatment of progressive supranuclear palsy: a narrative review. Pharmacotherapies for the treatment of progressive supranuclear palsy: a narrative review. Neurol Ther. 2024;13(4):975\u20131013. https:\/\/doi.org\/10.1007\/s40120-024-00614-9.","journal-title":"Neurol Ther"},{"issue":"20","key":"8022_CR8","doi-asserted-by":"publisher","first-page":"11234","DOI":"10.3390\/ijms222011234","volume":"22","author":"G Palermo","year":"2021","unstructured":"Palermo G, Giannoni S, Bellini G, et al Dopamine transporter imaging, current status of a potential biomarker: a comprehensive review. Int J Mol Sci. 2021;22(20):11234. . https:\/\/doi.org\/10.3390\/ijms222011234.","journal-title":"Int J Mol Sci"},{"issue":"8","key":"8022_CR9","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.2967\/jnumed.112.105379","volume":"54","author":"K Tatsch","year":"2013","unstructured":"Tatsch K, Poepperl G Nigrostriatal dopamine terminal imaging with dopamine transporter SPECT: an update. J Nucl Med. 2013;54(8):1331\u20138. https:\/\/doi.org\/10.2967\/jnumed.112.105379.","journal-title":"J Nucl Med"},{"issue":"1","key":"8022_CR10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1600-0404.2011.01583.x","volume":"126","author":"D Contrafatto","year":"2012","unstructured":"Contrafatto D, Mostile G, Nicoletti A, et al. [123I]FP-CIT-SPECT asymmetry index to differentiate Parkinson\u2019s disease from vascular parkinsonism. Acta Neurol Scand. 2012;126(1):12\u20136. https:\/\/doi.org\/10.1111\/j.1600-0404.2011.01583.x.","journal-title":"Acta Neurol Scand"},{"issue":"2","key":"8022_CR11","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1136\/jnnp-2012-302618","volume":"84","author":"S Ben\u00edtez-Rivero","year":"2013","unstructured":"Ben\u00edtez-Rivero S, Marin-Oyaga V, Garc\u00eda-Solis D, et al Clinical features and 123I-FP-CIT SPECT imaging in vascular parkinsonism and Parkinson\u2019s disease. J Neurol Neurosurg Psychiatry. 2013;84(2):122\u20139. https:\/\/doi.org\/10.1136\/jnnp-2012-302618.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"8022_CR12","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s00259-014-2882-8","volume":"42","author":"I Huertas-Fern\u00e1ndez","year":"2015","unstructured":"Huertas-Fern\u00e1ndez I, Garc\u00eda-G\u00f3mez FJ, Garc\u00eda-Sol\u00eds D, et al. Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson\u2019s disease using [123I]FP- CIT SPECT. Eur J Nucl Med Mol Imaging. 2015;42(1):112\u20139. https:\/\/doi.org\/10.1007\/s00259-014-2882-8.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"3","key":"8022_CR13","doi-asserted-by":"publisher","first-page":"399","DOI":"10.2967\/jnumed.111.095224","volume":"53","author":"M Oh","year":"2012","unstructured":"Oh M, Kim JS, Kim JY, et al. Subregional Patterns of Preferential Striatal Dopamine Transporter Loss Differ in Parkinson Disease, Progressive Supranuclear Palsy, and Multiple- System Atrophy. J Nucl Med. 2012;53(3):399\u2013406. https:\/\/doi.org\/10.2967\/jnumed.111.095224.","journal-title":"J Nucl Med"},{"key":"8022_CR14","doi-asserted-by":"publisher","first-page":"572976","DOI":"10.3389\/fneur.2020.572976","volume":"11","author":"U Saeed","year":"2020","unstructured":"Saeed U, Lang A, Masellis M Neuroimaging advances in Parkinson\u2019s disease and atypical parkinsonian syndromes. Front Neurol. 2020;11:572976. https:\/\/doi.org\/10.3389\/fneur.2020.572976.","journal-title":"Front Neurol"},{"issue":"3","key":"8022_CR15","doi-asserted-by":"publisher","first-page":"145","DOI":"10.33160\/yam.2018.09.001","volume":"61","author":"T Ogawa","year":"2018","unstructured":"Ogawa T, Fujii S, Kuya K, et al Role of Neuroimaging on Differentiation of Parkinson\u2019s Disease and Its Related Diseases. Yonago Acta Med. 2018;61(3):145\u201355. https:\/\/doi.org\/10.33160\/yam.2018.09.001.","journal-title":"Yonago Acta Med"},{"issue":"6","key":"8022_CR16","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/jon.12530","volume":"28","author":"M Matesan","year":"2018","unstructured":"Matesan M, Gaddikeri S, Longfellow K, et al. I-123 DaTscan SPECT Brain Imaging in Parkinsonian Syndromes: Utility of the Putamen-to-Caudate Ratio. J Neuroimaging. 2018;28(6):629\u201334. https:\/\/doi.org\/10.1111\/jon.12530.","journal-title":"J Neuroimaging"},{"issue":"7","key":"8022_CR17","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1007\/s00415-019-09330-z","volume":"266","author":"N Nicastro","year":"2019","unstructured":"Nicastro N, Wegrzyk J, Preti MG, et al Classification of degenerative parkinsonism subtypes by support-vector-machine analysis and striatal 123I-FP-CIT indices. J Neurol. 2019;266(7):1771\u201381. https:\/\/doi.org\/10.1007\/s00415-019-09330-z.","journal-title":"J Neurol"},{"key":"8022_CR18","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.neuroimage.2017.08.009","volume":"161","author":"I van Huertas","year":"2017","unstructured":"Huertas I, Oldehinkel M, van Oort ESB, et al. A Bayesian spatial model for neuroimaging data based on biologically informed basis functions. NeuroImage. 2017;161:134\u201348. https:\/\/doi.org\/10.1016\/j.neuroimage.2017.08.009.","journal-title":"NeuroImage"},{"issue":"6","key":"8022_CR19","doi-asserted-by":"publisher","first-page":"e296","DOI":"10.1097\/RLU.0000000000003609","volume":"46","author":"MA Labrador-Espinosa","year":"2021","unstructured":"Labrador-Espinosa MA, Grothe MJ, Mac\u00edas-Garc\u00eda D, et al. Levodopa-Induced Dyskinesia in Parkinson Disease Specifically Associates With Dopaminergic Depletion in Sensorimotor-Related Functional Subregions of the Striatum. Clin Nucl Med. 2021;46(6):e296\u2013306. https:\/\/doi.org\/10.1097\/RLU.0000000000003609.","journal-title":"Clin Nucl Med"},{"key":"8022_CR20","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1093\/cercor\/bhs397","volume":"24","author":"AC Tziortzi","year":"2014","unstructured":"Tziortzi AC, Haber SN, Searle GE, et al. Connectivity-based functional analysis of dopamine release in the striatum using diffusion-weighted MRI and positron emission tomography. Cereb Cortex. 2014;24:1165\u201377. https:\/\/doi.org\/10.1093\/cercor\/bhs397.","journal-title":"Cereb Cortex"},{"issue":"2","key":"8022_CR21","doi-asserted-by":"publisher","first-page":"243","DOI":"10.2214\/AJR.19.21088","volume":"213","author":"KP Banks","year":"2019","unstructured":"Banks KP, Peacock JG, Clemenshaw MN, et al Optimizing the Diagnosis of Parkinsonian Syndromes With 123I-Ioflupane Brain SPECT. AJR Am J Roentgenol. 2019;213(2):243\u201353. https:\/\/doi.org\/10.2214\/AJR.19.21088.","journal-title":"AJR Am J Roentgenol"},{"issue":"8","key":"8022_CR22","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1007\/s00259-020-04817-8","volume":"47","author":"S Morbelli","year":"2020","unstructured":"Morbelli S, Esposito G, Arbizu J, et al EANM practice guideline\/SNMMI procedure standard for dopaminergic imaging in Parkinsonian syndromes 1.0. Eur J Nucl Med Mol Imaging. 2020;47(8):1885\u2013912. https:\/\/doi.org\/10.1007\/s00259-020-04817-8.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"2","key":"8022_CR23","doi-asserted-by":"publisher","first-page":"e230133","DOI":"10.1148\/rg.230133","volume":"44","author":"MK Mercer","year":"2024","unstructured":"Mercer MK, Revels J, Blacklock LC, et al Practical overview of 123I-ioflupane imaging in parkinsonian syndromes. Radiographics. 2024;44(2):e230133. https:\/\/doi.org\/10.1148\/rg.230133.","journal-title":"Radiographics"},{"issue":"6","key":"8022_CR24","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/mds.29005","volume":"37","author":"GK Wenning","year":"2022","unstructured":"Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022;37(6):1131\u201348. https:\/\/doi.org\/10.1002\/mds.29005.","journal-title":"Mov Disord"},{"issue":"12","key":"8022_CR25","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov Disord. 2015;30(12):1591\u2013601. https:\/\/doi.org\/10.1002\/mds.26424.","journal-title":"Mov Disord"},{"issue":"6","key":"8022_CR26","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(6):853\u201364. https:\/\/doi.org\/10.1002\/mds.26987.","journal-title":"Mov Disord"},{"issue":"5","key":"8022_CR27","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1212\/WNL.0b013e31827f0fd1","volume":"80","author":"MJ Armstrong","year":"2013","unstructured":"Armstrong MJ, Litvan I, Lang AE, et al Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80(5):496\u2013503. https:\/\/doi.org\/10.1212\/WNL.0b013e31827f0fd1.","journal-title":"Neurology"},{"key":"8022_CR28","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.remn.2013.02.009","volume":"32","author":"FJ Garc\u00eda-G\u00f3mez","year":"2013","unstructured":"Garc\u00eda-G\u00f3mez FJ, Garc\u00eda-Sol\u00eds D, Luis-Sim\u00f3n FJ, et al Elaboration of the SPMtemplate for the standardization of SPECT images with 123I-Ioflupane. Rev Esp Med Nucl Imagen Mol Engl Ed. 2013;32:350\u20136. https:\/\/doi.org\/10.1016\/j.remn.2013.02.009.","journal-title":"Rev Esp Med Nucl Imagen Mol Engl Ed"},{"key":"8022_CR29","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 Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533\u20139. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600493.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"8022_CR30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.neuroimage.2010.06.044","volume":"54","author":"AC Tziortzi","year":"2011","unstructured":"Tziortzi AC, Searle GE, Tzimopoulou S, et al Imaging dopamine receptors in humans with [11 C]-(+)-PHNO: dissection of D3 signal and anatomical delineation of binding. NeuroImage. 2011;54(1):264\u201377. https:\/\/doi.org\/10.1016\/j.neuroimage.2010.06.044.","journal-title":"NeuroImage"},{"issue":"1","key":"8022_CR31","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/RLU.0000000000002869","volume":"45","author":"I Apostolova","year":"2020","unstructured":"Apostolova I, Lange C, Frings L, et al Nigrostriatal degeneration in the cognitive part of the striatum in Parkinson disease is associated with frontomedial hypometabolism. Clin Nucl Med. 2020;45(1):10\u20136. https:\/\/doi.org\/10.1097\/RLU.0000000000002869.","journal-title":"Clin Nucl Med"},{"key":"8022_CR32","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/s00702-017-1747-2","volume":"124","author":"D K\u00fcbler","year":"2017","unstructured":"K\u00fcbler D, Schroll H, Buchert R, et al Cognitive performance correlates with the degree of dopaminergic degeneration in the associative part of the striatum in non-demented Parkinson\u2019s patients. J Neural Transm (Vienna). 2017;124:1073\u201381. https:\/\/doi.org\/10.1007\/s00702-017-1747-2.","journal-title":"J Neural Transm (Vienna)"},{"issue":"4","key":"8022_CR33","doi-asserted-by":"publisher","first-page":"980","DOI":"10.3390\/tomography7040081","volume":"7","author":"M Neill","year":"2021","unstructured":"Neill M, Fisher JM, Brand C, et al. Practical Application of DaTQUANT with Optimal Threshold for Diagnostic Accuracy of Dopamine Transporter SPECT. Tomography. 2021;7(4):980\u20139. https:\/\/doi.org\/10.3390\/tomography7040081.","journal-title":"Tomography"},{"issue":"4","key":"8022_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11040453","volume":"11","author":"M Song","year":"2021","unstructured":"Song M, Jung H, Lee S, et al. Diagnostic classification and biomarker identification of Alzheimer\u2019s disease with random forest algorithm. Brain Sci. 2021;11(4):453. https:\/\/doi.org\/10.3390\/brainsci11040453.","journal-title":"Brain Sci"},{"issue":"1","key":"8022_CR35","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1613\/jair.953","volume":"16","author":"NV Chawla","year":"2002","unstructured":"Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP SMOTE: synthetic minority over-sampling technique. J Artif Intell Res. 2002;16(1):321\u201357. https:\/\/doi.org\/10.1613\/jair.953.","journal-title":"J Artif Intell Res"},{"issue":"2","key":"8022_CR36","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","volume":"24","author":"H Del Braak","year":"2003","unstructured":"Braak H, Del Tredici K, R\u00fcb U, et al Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol Aging. 2003;24(2):197\u2013211. . https:\/\/doi.org\/10.1016\/S0197-4580(02)00065-9.","journal-title":"Neurobiol Aging"},{"issue":"11","key":"8022_CR37","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1002\/mds.22207","volume":"23","author":"GG Kovacs","year":"2008","unstructured":"Kovacs GG, Milenkovic IJ, Preusser M, et al Nigral burden of alpha-synuclein correlates with striatal dopamine deficit. Mov Disord. 2008;23(11):1608\u201312. https:\/\/doi.org\/10.1002\/mds.22207.","journal-title":"Mov Disord"},{"issue":"4","key":"8022_CR38","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/ana.410380407","volume":"38","author":"JP Seibyl","year":"1995","unstructured":"Seibyl JP, Marek KL, Quinlan D, et al Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson\u2019s disease. Ann Neurol. 1995;38(4):589\u201398. https:\/\/doi.org\/10.1002\/ana.410380407.","journal-title":"Ann Neurol"},{"issue":"11","key":"8022_CR39","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.3390\/biomedicines11112893","volume":"26","author":"J Villena-Salinas","year":"2023","unstructured":"Villena-Salinas J, Ortega-Lozano SJ, Amrani-Raissouni T, et al Follow-Up Findings in Multiple System Atrophy from [123I]Ioflupane Single-Photon Emission Computed Tomography (SPECT): A Prospective Study. Biomedicines. 2023;26(11):2893. https:\/\/doi.org\/10.3390\/biomedicines11112893.","journal-title":"Biomedicines"},{"issue":"9","key":"8022_CR40","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1007\/s002590050295","volume":"25","author":"C Messa","year":"1998","unstructured":"Messa C, Volont\u00e9 MA, Fazio F, et al Differential distribution of striatal [ 123 I]beta-CIT in Parkinson\u2019s disease and progressive supranuclear palsy, evaluated with single-photon emission tomography. Eur J Nucl Med. 1998;25(9):1270\u20136. https:\/\/doi.org\/10.1007\/s002590050295.","journal-title":"Eur J Nucl Med"},{"issue":"4","key":"8022_CR41","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/mds.21907","volume":"23","author":"KE Murphy","year":"2008","unstructured":"Murphy KE, Karaconji T, Hardman CD, et al Excessive dopamine neuron loss in progressive supranuclear palsy. Mov Disord. 2008;23(4):607\u201310. https:\/\/doi.org\/10.1002\/mds.21907.","journal-title":"Mov Disord"},{"issue":"2","key":"8022_CR42","doi-asserted-by":"publisher","first-page":"e96","DOI":"10.1097\/RLU.0000000000001477","volume":"42","author":"N Nicastro","year":"2017","unstructured":"Nicastro N, Garibotto V, Allali G, et al Added value of combined semi-quantitative and visual [123I]-FP-CIT SPECT analyses for the diagnosis of dementia with Lewy bodies. Clin Nucl Med. 2017;42(2):e96\u2013102. https:\/\/doi.org\/10.1097\/RLU.0000000000001477.","journal-title":"Clin Nucl Med"},{"issue":"6","key":"8022_CR43","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1111\/ane.12932","volume":"137","author":"LL Bu","year":"2018","unstructured":"Bu LL, Liu FT, Jiang CF, et al. Patterns of dopamine transporter imaging in subtypes of multiple system atrophy. Acta Neurol Scand. 2018;137(6):620\u20138. https:\/\/doi.org\/10.1111\/ane.12932.","journal-title":"Acta Neurol Scand"},{"issue":"3","key":"8022_CR44","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00259-015-3191-6","volume":"43","author":"HW Kim","year":"2016","unstructured":"Kim HW, Kim JS, Oh M, et al Different loss of dopamine transporter according to subtype of multiple system atrophy. Eur J Nucl Med Mol Imaging. 2016;43(3):517\u201325. https:\/\/doi.org\/10.1007\/s00259-015-3191-6.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"8022_CR45","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.parkreldis.2019.02.006","volume":"63","author":"S Vergnet","year":"2019","unstructured":"Vergnet S, Hives F, Foubert-Samier A, et al Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type. Parkinsonism Relat Disord. 2019;63:199\u2013203. . https:\/\/doi.org\/10.1016\/j.parkreldis.2019.02.006.","journal-title":"Parkinsonism Relat Disord"},{"issue":"18","key":"8022_CR46","doi-asserted-by":"publisher","first-page":"e2006","DOI":"10.1212\/WNL.0000000000013172","volume":"99","author":"T Wirth","year":"2022","unstructured":"Wirth T, Namer IJ, Monga B, et al Progression of nigrostriatal denervation in cerebellar multiple system atrophy. Neurology. 2022;99(18):e2006\u2013e. 2014 10.1212\/WNL.0000000000013172. https:\/\/doi.org\/10.1212\/WNL.0000000000013172.","journal-title":"Neurology"},{"issue":"24","key":"8022_CR47","doi-asserted-by":"publisher","first-page":"e209759","DOI":"10.1212\/WNL.0000000000209612","volume":"102","author":"A Hastings","year":"2024","unstructured":"Hastings A, Mann DM, Lees AJ, et al Neuropathologic validation and diagnostic accuracy of presynaptic dopaminergic imaging in atypical parkinsonism. Neurology. 2024;102(24):e209759. . https:\/\/doi.org\/10.1212\/WNL.0000000000209612.","journal-title":"Neurology"},{"issue":"5","key":"8022_CR48","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s00702-025-02921-3","volume":"132","author":"WH Jost","year":"2025","unstructured":"Jost WH, Rau A, Brumberg J, et al Neuroimaging in multiple system atrophy: clinical implication and novel developments. J Neural Transm (Vienna). 2025;132(5):733\u201344. . https:\/\/doi.org\/10.1007\/s00702-025-02921-3.","journal-title":"J Neural Transm (Vienna)"},{"issue":"2","key":"8022_CR49","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2967\/jnmt.113.134940","volume":"42","author":"PH Kuo","year":"2014","unstructured":"Kuo PH, Lei HH, Avery R, et al. Evaluation of an Objective Striatal Analysis Program for Determining Laterality in Uptake of \u00b9\u00b2\u00b3I-Ioflupane SPECT Images: Comparison to Clinical Symptoms and to Visual Reads. J Nucl Med Technol. 2014;42(2):105\u20138. https:\/\/doi.org\/10.2967\/jnmt.113.134940.","journal-title":"J Nucl Med Technol"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08022-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-08022-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08022-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:31:48Z","timestamp":1790929908000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-08022-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["8022"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-08022-x","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"assertion":[{"value":"27 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"DMG has received honoraria from AbbVie and Merz. AAG has received honoraria from AbbVie, Bial, Merz, Italfarmaco, Esteve and Zambon. SJ has received honoraria from AbbVie, Bial, Merz, UCB, Italfarmaco, Orion and Zambon. LMD has received honoraria from AbbVie, Merz and Zambon. Paula FR has received support from GE HealthCare. PM has also received support for attending meetings and\/or travel or honorarium for lecturing from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon. The remaining authors declare that they have no relevant financial or non-financial interests to disclose.","order":1,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Hospital Universitario Virgen del Roc\u00edo.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from all alive participants during their clinical visits. For deceased patients, the ethics committees explicitly authorized the retrospective use of their imaging and clinical data without the need for additional consent.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}}]}}