{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:02:07Z","timestamp":1785409327368,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"crossref","award":["1292326N"],"award-info":[{"award-number":["1292326N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1292326N"],"award-info":[{"award-number":["1292326N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson\u2019s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in PD and (2) the comparative and combined diagnostic accuracy of striatal dopaminergic and cardiac sympathetic imaging in PD. Methods: We searched PubMed (October 2025) for studies assessing both a striatal dopaminergic and a cardiac sympathetic imaging biomarker in the same PD cohort, supplemented by citation chaining. Diagnostic accuracy studies were evaluated using QUADAS-2. Results: Nineteen studies met the inclusion criteria. Ten studies examined within-subject associations; six reported significant correlations ranging from weak to strong (\u03c1 ~0.2\u20130.8). Two studies observed a significant correlation for the akinetic-rigid subtype but not for the tremor-dominant subtype of PD. Ten studies compared diagnostic accuracies, five of which used pre-defined thresholds and consistently found higher sensitivity for [123I]FP-CIT SPECT (78\u2013100%) compared to [123I]MIBG scintigraphy (65\u201382%), but higher specificity for [123I]MIBG (range 75\u2013100%) than for [123I]FP-CIT (range 11\u201373%). Adding [123I]MIBG scintigraphy to [123I]FP-CIT SPECT generally increased specificity but had inconsistent effects on overall accuracy. QUADAS-2 revealed substantial risks of patient selection bias, data-driven thresholds, and limited blinding. Conclusions: Reported correlations between nigrostriatal dopaminergic degeneration and cardiac sympathetic denervation in PD are inconsistent, likely reflecting both methodological heterogeneity and real variation between phenotypes. There may be a stronger correlation in the akinetic-rigid phenotype. Dopaminergic imaging is more sensitive in early PD, while cardiac sympathetic imaging is more specific for differentiating PD from atypical Parkinsonian syndromes. However, study designs greatly restrict the generalizability of reported diagnostic accuracies.<\/jats:p>","DOI":"10.3390\/brainsci16050484","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:47:28Z","timestamp":1777546048000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Striatal Dopaminergic and Cardiac Sympathetic Imaging in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3475-1079","authenticated-orcid":false,"given":"Louis","family":"Versweyveld","sequence":"first","affiliation":[{"name":"Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-4121","authenticated-orcid":false,"given":"Greet","family":"Vanderlinden","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Delva","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-7245","authenticated-orcid":false,"given":"Koen","family":"Van Laere","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"},{"name":"Division of Nuclear Medicine, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1212\/WNL.0000000000000641","article-title":"Low clinical diagnostic accuracy of early vs advanced Parkinson disease: Clinicopathologic study","volume":"83","author":"Adler","year":"2014","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"286","DOI":"10.2967\/jnumed.124.268365","article-title":"Longitudinal Trajectory of Dopamine and Serotonin Transporters in Parkinson Disease","volume":"66","author":"Song","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.tins.2016.10.008","article-title":"The Threshold Theory for Parkinson\u2019s Disease","volume":"40","author":"Engelender","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_5","first-page":"1921","article-title":"Progressive Olfactory Impairment and Cardiac Sympathetic Denervation in REM Sleep Behavior Disorder","volume":"12","author":"Janzen","year":"2022","journal-title":"J. Park. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106101","DOI":"10.1016\/j.parkreldis.2024.106101","article-title":"Brain-first vs. body-first Parkinson\u2019s disease: An update on recent evidence","volume":"122","author":"Horsager","year":"2024","journal-title":"Park. Relat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.7861\/clinmedicine.16-4-371","article-title":"Imaging in Parkinson\u2019s disease","volume":"16","author":"Pagano","year":"2016","journal-title":"Clin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pitton Rissardo, J., and Fornari Caprara, A.L. (2023). Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson\u2019s Disease: A Comprehensive Review. Brain Sci., 13.","DOI":"10.3390\/brainsci13101471"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jns.2017.01.042","article-title":"Combined use of dopamine transporter imaging (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson\u2019s disease","volume":"375","author":"Yoshii","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1552-6569.2012.00774.x","article-title":"Iodine-123 Metaiodobenzylguanidine Scintigraphy and Iodine-123 Ioflupane Single Photon Emission Computed Tomography in Lewy Body Diseases: Complementary or Alternative Techniques?","volume":"24","author":"Treglia","year":"2014","journal-title":"J. Neuroimaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.5692\/clinicalneurol.cn-000848","article-title":"[123I]-Ioflupane SPECT in combination with MIBG myocardial scintigraphy in Parkinson\u2019s disease: A case series study","volume":"56","author":"Yamada","year":"2016","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/MNM.0000000000000898","article-title":"Usefulness of the combination of iodine-123-metaiodobenzylguanidine scintigraphy and iodine-123-ioflupane scintigraphy in new-onset Parkinson\u2019s disease","volume":"39","author":"Okada","year":"2018","journal-title":"Nucl. Med. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1097\/RLU.0000000000003098","article-title":"Is There Any Clinical Value of Adding 123I-Metaiodobenzylguanidine Myocardial Scintigraphy to 123I-Ioflupane (DaTscan) in the Differential Diagnosis of Parkinsonism?","volume":"45","author":"Stathaki","year":"2020","journal-title":"Clin. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"De Feo, M.S., Frantellizzi, V., Locuratolo, N., Di Rocco, A., Farcomeni, A., Pauletti, C., Marongiu, A., Lazri, J., Nuvoli, S., and Fattapposta, F. (2023). Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson\u2019s Disease: A Multicenter Study. Life, 13.","DOI":"10.3390\/life13081786"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.33160\/yam.2018.06.004","article-title":"The Utility of the Combined Use of 123I-FP-CIT and 123I-MIBG Myocardial Scintigraphy in Differentiating Parkinson\u2019s Disease from Other Parkinsonian Syndromes","volume":"61","author":"Matsusue","year":"2018","journal-title":"Yonago Acta Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1007\/s00259-020-05168-0","article-title":"A diagnostic strategy for Parkinsonian syndromes using quantitative indices of DAT SPECT and MIBG scintigraphy: An investigation using the classification and regression tree analysis","volume":"48","author":"Iwabuchi","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/MNM.0000000000000674","article-title":"The utility of the combination of a SPECT study with [123I]-FP-CIT of dopamine transporters and [123I]-MIBG myocardial scintigraphy in differentiating Parkinson disease from other degenerative parkinsonian syndromes","volume":"38","author":"Uyama","year":"2017","journal-title":"Nucl. Med. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2967\/jnumed.110.086959","article-title":"Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: A multidimensional statistical approach","volume":"52","author":"Antke","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.parkreldis.2019.02.012","article-title":"Striatal dopamine activity and myocardial 123I-metaiodobenzylguanidine uptake in early Parkinson\u2019s disease","volume":"63","author":"Oh","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_23","first-page":"1","article-title":"Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson\u2019s Disease","volume":"1","author":"Spiegel","year":"2007","journal-title":"Open Neurol. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/mds.20369","article-title":"FP-CIT and MIBG scintigraphy in early Parkinson\u2019s disease","volume":"20","author":"Spiegel","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2176\/nmc.oa.2015-0234","article-title":"Importance of 123I-ioflupane SPECT and Myocardial MIBG Scintigraphy to Determine the Candidate of Deep Brain Stimulation for Parkinson\u2019s Disease","volume":"56","author":"Asahi","year":"2016","journal-title":"Neurol. Med. Chir."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102956","DOI":"10.1016\/j.neucli.2024.102956","article-title":"Correlation with sympathetic skin response, 123I-MIBG scintigraphy, and 123I-FP-CIT SPECT in Parkinson\u2019s disease","volume":"54","author":"Ozawa","year":"2024","journal-title":"Neurophysiol. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e26995","DOI":"10.1097\/MD.0000000000026995","article-title":"Intrasubject relationship between striatal 18F-FP-CIT uptake and cardiac 123I-MIBG uptake differs by motor subtype in early Parkinson disease","volume":"100","author":"Jang","year":"2021","journal-title":"Medicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s12149-013-0702-z","article-title":"Cardiac sympathetic denervation is not related to nigrostriatal degeneration in Parkinson\u2019s disease","volume":"27","author":"Chiaravalloti","year":"2013","journal-title":"Ann. Nucl. Med."},{"key":"ref_29","first-page":"1769","article-title":"PET Measurement of Cardiac and Nigrostriatal Denervation in Parkinsonian Syndromes","volume":"47","author":"Raffel","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00259-009-1202-1","article-title":"Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson\u2019s disease who were diagnosed with dopamine PET","volume":"37","author":"Ishibashi","year":"2010","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/mds.21499","article-title":"Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson\u2019s disease","volume":"22","author":"Spiegel","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.jocn.2010.12.024","article-title":"Differences in myocardial sympathetic degeneration and the clinical features of the subtypes of Parkinson\u2019s disease","volume":"18","author":"Chung","year":"2011","journal-title":"J. Clin. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1468-1331.2009.02898.x","article-title":"Differences in nigro-striatal impairment in clinical variants of early Parkinson\u2019s disease: Evidence from a FP-CIT SPECT study","volume":"17","author":"Rossi","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1002\/mds.10579","article-title":"Correlation of dopamine transporter imaging with parkinsonian motor handicap: How close is it?","volume":"18","author":"Pirker","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41593-025-01910-9","article-title":"Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals","volume":"28","author":"Andersen","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/RLU.0000000000002424","article-title":"Initial Versus Follow-up Sequential Myocardial 123I-MIBG Scintigraphy to Discriminate Parkinson Disease From Atypical Parkinsonian Syndromes","volume":"44","author":"Ryu","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/mds.30255","article-title":"Normal [18F]FE-PE2I PET in Patients with Persistent Diagnostic Uncertainty after Abnormal [123I]FP-CIT SPECT","volume":"40","author":"Dhadamus","year":"2025","journal-title":"Mov. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15069","DOI":"10.1038\/s41598-023-42135-9","article-title":"Diagnostic accuracy of 18F-FP-CIT PET for clinically uncertain Parkinsonian syndrome","volume":"13","author":"Oh","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.parkreldis.2012.01.009","article-title":"123I-MIBG myocardial scintigraphy for differentiating Parkinson\u2019s disease from other neurodegenerative parkinsonism: A systematic review and meta-analysis","volume":"18","author":"Orimo","year":"2012","journal-title":"Park. Relat. Disord."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/5\/484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:26:52Z","timestamp":1777696012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/5\/484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["brainsci16050484"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16050484","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}