Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Department of Biomedical Imaging and Image guided Therapy Medical University of Vienna Austria

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Nuclear Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Radiology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Radiodiagnostic Department Na Homolce Hospital Prague Czech Republic

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Acosta‐Cabronero, J. , Betts, M. J. , Cardenas‐Blanco, A. , Yang, S. , & Nestor, P. J. (2016). In vivo MRI mapping of brain iron deposition across the adult lifespan. Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 36, 364–374. PubMed PMC

Acosta‐Cabronero, J. , Cardenas‐Blanco, A. , Betts, M. J. , Butryn, M. , Valdes‐Herrera, J. P. , Galazky, I. , & Nestor, P. J. (2017). The whole‐brain pattern of magnetic susceptibility perturbations in Parkinson's disease. Brain, 140, 118–131. PubMed

Acosta‐Cabronero, J. , Milovic, C. , Mattern, H. , Tejos, C. , Speck, O. , & Callaghan, M. F. (2018). A robust multi‐scale approach to quantitative susceptibility mapping. NeuroImage, 183, 7–24. PubMed PMC

Al‐Qassabi, A. , Tsao, T.‐S. , Racolta, A. , Kremer, T. , Cañamero, M. , Belousov, A. , Santana, M. A. , Beck, R. C. , Zhang, H. , Meridew, J. , Pugh, J. , Lian, F. , Robida, M. D. , Ritter, M. , Czech, C. , Beach, T. G. , Pestic‐Dragovich, L. , Taylor, K. I. , Zago, W. , … Postuma, R. B. (2021). Immunohistochemical detection of synuclein pathology in skin in idiopathic rapid eye movement sleep behavior disorder and Parkinsonism. Movement Disorders, 36, 895–904. PubMed PMC

Arnaldi, D. , Chincarini, A. , Hu, M. T. , Sonka, K. , Boeve, B. , Miyamoto, T. , Puligheddu, M. , de Cock, V. C. , Terzaghi, M. , Plazzi, G. , Tachibana, N. , Morbelli, S. , Rolinski, M. , Dusek, P. , Lowe, V. , Miyamoto, M. , Figorilli, M. , Verbizier, D. , Bossert, I. , … Nobili, F. (2021). Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain: A Journal of Neurology, 144, 278–287. PubMed PMC

Avants, B. B. , Epstein, C. L. , Grossman, M. , & Gee, J. C. (2008). Symmetric diffeomorphic image registration with cross‐correlation: Evaluating automated labeling of elderly and neurodegenerative brain. Medical Image Analysis, 12, 26–41. PubMed PMC

Bae, Y. J. , Kim, J. M. , Kim, K. J. , Kim, E. , Park, H. S. , Kang, S. Y. , Yoon, I. Y. , Lee, J. Y. , Jeon, B. , & Kim, S. E. (2018). Loss of Substantia nigra hyperintensity at 3.0‐T MR imaging in idiopathic REM sleep behavior disorder: Comparison with 123I‐FP‐CIT SPECT. Radiology, 287, 285–293. PubMed

Barber, T. R. , Griffanti, L. , Bradley, K. M. , McGowan, D. R. , Lo, C. , Mackay, C. E. , Hu, M. T. , & Klein, J. C. (2020). Nigrosome 1 imaging in REM sleep behavior disorder and its association with dopaminergic decline. Annals of Clinical Translational Neurology, 7, 26–35. PubMed PMC

Barber, T. R. , Lawton, M. , Rolinski, M. , Evetts, S. , Baig, F. , Ruffmann, C. , Gornall, A. , Klein, J. C. , Lo, C. , Dennis, G. , Bandmann, O. , Quinnell, T. , Zaiwalla, Z. , Ben‐Shlomo, Y. , & Hu, M. T. M. (2017). Prodromal Parkinsonism and neurodegenerative risk stratification in REM sleep behavior disorder. Sleep, 40, zsx071. PubMed PMC

Barbosa, J. H. O. , Santos, A. C. , Tumas, V. , Liu, M. , Zheng, W. , Haacke, E. M. , & Salmon, C. E. G. (2015). Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2*. Magnetic Resonance Imaging, 33, 559–565. PubMed

Betts, M. J. , Acosta‐Cabronero, J. , Cardenas‐Blanco, A. , Nestor, P. J. , & Düzel, E. (2016). High‐resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7T. NeuroImage, 138, 43–63. PubMed

Biondetti, E. , Santin, M. D. , Valabrègue, R. , Mangone, G. , Gaurav, R. , Pyatigorskaya, N. , Hutchison, M. , Yahia‐Cherif, L. , Villain, N. , Habert, M. O. , Arnulf, I. , Leu‐Semenescu, S. , Dodet, P. , Vila, M. , Corvol, J. C. , Vidailhet, M. , & Lehéricy, S. (2021). The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease. Brain, 144, 3114–3125. PubMed PMC

Brammerloh, M. , Morawski, M. , Friedrich, I. , Reinert, T. , Lange, C. , Pelicon, P. , Vavpetič, P. , Jankuhn, S. , Jäger, C. , Alkemade, A. , Balesar, R. , Pine, K. , Gavriilidis, F. , Trampel, R. , Reimer, E. , Arendt, T. , Weiskopf, N. , & Kirilina, E. (2021). Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry. NeuroImage, 239, 118255. PubMed PMC

Bušková, J. , Ibarburu, V. , Šonka, K. , & Růžička, E. (2016). Screening for REM sleep behavior disorder in the general population. Sleep Medicine, 24, 147. PubMed

Campabadal, A. , Segura, B. , Junque, C. , & Iranzo, A. (2021). Structural and functional magnetic resonance imaging in isolated REM sleep behavior disorder: A systematic review of studies using neuroimaging software. Sleep Medicine Reviews, 59, 101495. PubMed

Campabadal, A. , Segura, B. , Junque, C. , Serradell, M. , Abos, A. , Uribe, C. , Baggio, H. C. , Gaig, C. , Santamaria, J. , Compta, Y. , Bargallo, N. , & Iranzo, A. (2019). Cortical gray matter and hippocampal atrophy in idiopathic rapid eye movement sleep behavior disorder. Frontiers in Neurology, 10, 312. PubMed PMC

Chen, Q. , Boeve, B. F. , Forghanian‐Arani, A. , Senjem, M. L. , Jack, C. R., Jr. , Przybelski, S. A. , Lesnick, T. G. , Kremers, W. K. , Fields, J. A. , Schwarz, C. G. , Gunter, J. L. , Trzasko, J. D. , Graff‐Radford, J. , Savica, R. , Knopman, D. S. , Dickson, D. W. , Ferman, T. J. , Graff‐Radford, N. , Petersen, R. C. , & Kantarci, K. (2021). MRI quantitative susceptibility mapping of the substantia nigra as an early biomarker for Lewy body disease. Journal of Neuroimaging, 31, 1020–1027. PubMed PMC

Chen, Q. , Chen, Y. , Zhang, Y. , Wang, F. , Yu, H. , Zhang, C. , Jiang, Z. , & Luo, W. (2019). Iron deposition in Parkinson's disease by quantitative susceptibility mapping. BMC Neuroscience, 20, 23. PubMed PMC

Damier, P. , Hirsch, E. C. , Agid, Y. , & Graybiel, A. M. (1999). The substantia nigra of the human brain. II. Patterns of loss of dopamine‐containing neurons in Parkinson's disease. Brain Journal of Neurology, 122(Pt 8), 1437–1448. PubMed

Darcourt, J. , Booij, J. , Tatsch, K. , Varrone, A. , Vander Borght, T. , Kapucu, Ö. L. , Någren, K. , Nobili, F. , Walker, Z. , & van Laere, K. (2010). EANM procedure guidelines for brain neurotransmission SPECT using (123)I‐labelled dopamine transporter ligands, version 2. European Journal of Nuclear Medicine and Molecular Imaging, 37, 443–450. PubMed

De Marzi, R. , Seppi, K. , Högl, B. , Müller, C. , Scherfler, C. , Stefani, A. , Iranzo, A. , Tolosa, E. , Santamarìa, J. , Gizewski, E. , Schocke, M. , Skalla, E. , Kremser, C. , & Poewe, W. (2016). Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility‐weighted imaging in idiopathic rapid eye movement sleep behavior disorder. Annals of Neurology, 79, 1026–1030. PubMed

Deistung, A. , Schäfer, A. , Schweser, F. , Biedermann, U. , Turner, R. , & Reichenbach, J. R. (2013). Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude‐, phase‐, and R2*‐imaging at ultra‐high magnetic field strength. NeuroImage, 65, 299–314. PubMed

Doty, R. L. , Shaman, P. , & Dann, M. (1984). Development of the University of Pennsylvania Smell Identification Test: A standardized microencapsulated test of olfactory function. Physiology & Behavior, 32, 489–502. PubMed

Du, G. , Liu, T. , Lewis, M. M. , Kong, L. , Wang, Y. , Connor, J. , Mailman, R. B. , & Huang, X. (2016). Quantitative susceptibility mapping of the midbrain in Parkinson's disease. Movement Disorders, 31, 317–324. PubMed PMC

Dusek, P. , Bezdicek, O. , Brožová, H. , Antonia, I. D. , Dostálová, S. , Havránková, P. , Klempír, J. , Mana, J. , Mašková, J. , Nepožitek, J. , Roth, J. , Perinova, P. , Ruzicka, F. , Serranová, T. , Trnka, J. , Ulmanová, O. , Zogala, D. , Jech, R. , Šonka, K. , & Růžička, E. (2020). Clinical characteristics of newly diagnosed Parkinson's disease patients included in the longitudinal BIO‐PD study. Ceská a Slovenská Neurologie a Neurochirurgie, 83(116), 633–639.

Dusek, P. , Lescinskij, A. , Ruzicka, F. , Acosta‐Cabronero, J. , Bruha, R. , Sieger, T. , Hajek, M. , & Dezortova, M. (2021). Associations of brain atrophy and cerebral iron accumulation at MRI with clinical severity in Wilson disease. Radiology, 299, 662–672. PubMed

Dušek, P. , Ibarburu, V. L. L. , Bezdicek, O. , Dall'antonia, I. , Dostálová, S. , Kovalská, P. , Krupička, R. , Nepožitek, J. , Nikolai, T. , Novotný, M. , Peřinová, P. , Rusz, J. , Serranová, T. , Tykalová, T. , Ulmanová, O. , Mecková, Z. , Ptáčník, V. , Trnka, J. , Zogala, D. , … Šonka, K. (2019). Relations of non‐motor symptoms and dopamine transporter binding in REM sleep behavior disorder. Scientific Reports, 9, 15463. PubMed PMC

Eckstein, K. , Bachrata, B. , Hangel, G. , Widhalm, G. , Enzinger, C. , Barth, M. , Trattnig, S. , & Robinson, S. D. (2021). Improved susceptibility weighted imaging at ultra‐high field using bipolar multi‐echo acquisition and optimized image processing: CLEAR‐SWI. NeuroImage, 237, 118175. PubMed PMC

Ewert, S. , Horn, A. , Finkel, F. , Li, N. , Kühn, A. A. , & Herrington, T. M. (2019). Optimization and comparative evaluation of nonlinear deformation algorithms for atlas‐based segmentation of DBS target nuclei. NeuroImage, 184, 586–598. PubMed PMC

Fereshtehnejad, S.‐M. , Romenets, S. R. , Anang, J. B. M. , Latreille, V. , Gagnon, J. F. , & Postuma, R. B. (2015). New clinical subtypes of Parkinson disease and their longitudinal progression: A prospective cohort comparison with other phenotypes. JAMA Neurology, 72, 863–873. PubMed

Fischl, B. , & Dale, A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences, 97, 11050–11055. PubMed PMC

Freeman, R. , Wieling, W. , Axelrod, F. B. , Benditt, D. G. , Benarroch, E. , Biaggioni, I. , Cheshire, W. P. , Chelimsky, T. , Cortelli, P. , Gibbons, C. H. , Goldstein, D. S. , Hainsworth, R. , Hilz, M. J. , Jacob, G. , Kaufmann, H. , Jordan, J. , Lipsitz, L. A. , Levine, B. D. , Low, P. A. , … van Dijk, J. G. (2011). Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clinical Autonomic Research, 21, 69–72. PubMed

Frosini, D. , Cosottini, M. , Donatelli, G. , Costagli, M. , Biagi, L. , Pacchetti, C. , Terzaghi, M. , Cortelli, P. , Arnaldi, D. , Bonanni, E. , Tosetti, M. , Bonuccelli, U. , & Ceravolo, R. (2017). Seven tesla MRI of the substantia nigra in patients with rapid eye movement sleep behavior disorder. Parkinsonism & Related Disorders, 43, 105–109. PubMed

Galbiati, A. , Verga, L. , Giora, E. , Zucconi, M. , & Ferini‐Strambi, L. (2019). The risk of neurodegeneration in REM sleep behavior disorder: A systematic review and meta‐analysis of longitudinal studies. Sleep Medicine Reviews, 43, 37–46. PubMed

Gaser, C. , Dahnke, R. , Thompson, P. M. , Kurth, F. , Luders, E. , & Alzheimer's Disease Neuroimaging Initiative . (2022). CAT – A computational anatomy toolbox for the analysis of structural MRI data. bioRxiv Preprint at. 10.1101/2022.06.11.495736 PubMed DOI PMC

Goetz, C. G. , Fahn, S. , Martinez‐Martin, P. , Poewe, W. , Sampaio, C. , Stebbins, G. T. , Stern, M. B. , Tilley, B. C. , Dodel, R. , Dubois, B. , Holloway, R. , Jankovic, J. , Kulisevsky, J. , Lang, A. E. , Lees, A. , Leurgans, S. , LeWitt, P. A. , Nyenhuis, D. , Olanow, C. W. , … LaPelle, N. (2007). Movement Disorder Society‐sponsored revision of the unified Parkinson's disease rating scale (MDS‐UPDRS): Process, format, and clinimetric testing plan. Movement Disorder, 22, 41–47. PubMed

Good, C. D. , Johnsrude, I. S. , Ashburner, J. , Henson, R. N. A. , Friston, K. J. , & Frackowiak, R. S. J. (2001). A voxel‐based morphometric study of ageing in 465 normal adult human brains. NeuroImage, 14, 21–36. PubMed

Goto, M. , Abe, O. , Miyati, T. , Aoki, S. , Takao, H. , Hayashi, N. , Mori, H. , Kunimatsu, A. , Ino, K. , Yano, K. , & Ohtomo, K. (2013). Association between iron content and gray matter missegmentation with voxel‐based morphometry in basal ganglia. Journal of Magnetic Resonance Imaging, 38, 958–962. PubMed

He, N. , Ling, H. , Ding, B. , Huang, J. , Zhang, Y. , Zhang, Z. , Liu, C. , Chen, K. , & Yan, F. (2015). Region‐specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping. Human Brain Mapping, 36, 4407–4420. PubMed PMC

Huddleston, D. E. , Langley, J. , Dusek, P. , He, N. , Faraco, C. C. , Crosson, B. , Factor, S. , & Hu, X. P. (2018). Imaging Parkinsonian pathology in Substantia nigra with MRI. Current Radiology Reports, 6, 15.

Iranzo, A. , Borrego, S. , Vilaseca, I. , Martí, C. , Serradell, M. , Sánchez‐Valle, R. , Kovacs, G. G. , Valldeoriola, F. , Gaig, C. , Santamaria, J. , Tolosa, E. , & Gelpi, E. (2018). α‐Synuclein aggregates in labial salivary glands of idiopathic rapid eye movement sleep behavior disorder. Sleep, 41, zsy101. PubMed

Keller, S. S. , Wilke, M. , Wieshmann, U. C. , Sluming, V. A. , & Roberts, N. (2004). Comparison of standard and optimized voxel‐based morphometry for analysis of brain changes associated with temporal lobe epilepsy. NeuroImage, 23, 860–868. PubMed

Kim, E. Y. , Sung, Y. H. , Shin, H. G. , Noh, Y. , Nam, Y. , & Lee, J. (2018). Diagnosis of early‐stage idiopathic Parkinson's disease using high‐resolution quantitative susceptibility mapping combined with histogram analysis in the Substantia nigra at 3 T. Journal of Clinical Neurology, 14, 90–97. PubMed PMC

Kim, Y. , Kim, Y. E. , Park, E. O. , Shin, C. W. , Kim, H. J. , & Jeon, B. (2018). REM sleep behavior disorder portends poor prognosis in Parkinson's disease: A systematic review. Journal of Clinical Neuroscience, 47, 6–13. PubMed

Lancione, M. , Donatelli, G. , del Prete, E. , Campese, N. , Frosini, D. , Cencini, M. , Costagli, M. , Biagi, L. , Lucchi, G. , Tosetti, M. , Godani, M. , Arnaldi, D. , Terzaghi, M. , Provini, F. , Pacchetti, C. , Cortelli, P. , Bonanni, E. , Ceravolo, R. , & Cosottini, M. (2022). Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies. NeuroImage, 260, 119454. PubMed

Langkammer, C. , Pirpamer, L. , Seiler, S. , Deistung, A. , Schweser, F. , Franthal, S. , Homayoon, N. , Katschnig‐Winter, P. , Koegl‐Wallner, M. , Pendl, T. , Stoegerer, E. M. , Wenzel, K. , Fazekas, F. , Ropele, S. , Reichenbach, J. R. , Schmidt, R. , & Schwingenschuh, P. (2016). Quantitative susceptibility mapping in Parkinson's disease. PLoS One, 11, e0162460. PubMed PMC

Langkammer, C. , Schweser, F. , Krebs, N. , Deistung, A. , Goessler, W. , Scheurer, E. , Sommer, K. , Reishofer, G. , Yen, K. , Fazekas, F. , Ropele, S. , & Reichenbach, J. R. (2012). Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study. NeuroImage, 62, 1593–1599. PubMed PMC

Lee, J. , Shmueli, K. , Fukunaga, M. , van Gelderen, P. , Merkle, H. , Silva, A. C. , & Duyn, J. H. (2010). Sensitivity of MRI resonance frequency to the orientation of brain tissue microstructure. Proceedings of the National Academy of Sciences, 107, 5130–5135. PubMed PMC

Lee, J.‐H. , Han, Y. H. , Cho, J. W. , Lee, J. S. , Lee, S. J. , Kim, D. J. , Kim, T. H. , Kang, B. M. , Kim, T. H. , & Mun, C. W. (2014). Evaluation of brain iron content in idiopathic REM sleep behavior disorder using quantitative magnetic resonance imaging. Parkinsonism & Related Disorders, 20, 776–778. PubMed

Li, G. , Zhai, G. , Zhao, X. , An, H. , Spincemaille, P. , Gillen, K. M. , Ku, Y. , Wang, Y. , Huang, D. , & Li, J. (2019). 3D texture analyses within the substantia nigra of Parkinson's disease patients on quantitative susceptibility maps and R2* maps. NeuroImage, 188, 465–472. PubMed

Lorio, S. , Lutti, A. , Kherif, F. , Ruef, A. , Dukart, J. , Chowdhury, R. , Frackowiak, R. S. , Ashburner, J. , Helms, G. , Weiskopf, N. , & Draganski, B. (2014). Disentangling in vivo the effects of iron content and atrophy on the ageing human brain. NeuroImage, 103, 280–289. PubMed PMC

Lotfipour, A. K. , Wharton, S. , Schwarz, S. T. , Gontu, V. , Schäfer, A. , Peters, A. M. , Bowtell, R. W. , Auer, D. P. , Gowland, P. A. , & Bajaj, N. P. S. (2012). High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson's disease. Journal of Magnetic Resonance Imaging, 35, 48–55. PubMed

Maskova J, Skoloudik D, Stofanikova P, Ibarburu V, Kemlink D, Zogala D, Trnka J, Krupicka R, Sonka K, Ruzicka E, Dusek P. (2020). Comparative study of the substantia nigra echogenicity and (123)I‐Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder. Sleep Med, 70, 116–123. PubMed

Miyata, M. , Kakeda, S. , Toyoshima, Y. , Ide, S. , Okada, K. , Adachi, H. , Wang, Y. , & Korogi, Y. (2019). Potential usefulness of signal intensity of cerebral gyri on quantitative susceptibility mapping for discriminating corticobasal degeneration from progressive supranuclear palsy and Parkinson's disease. Neuroradiology, 61, 1251–1259. PubMed

Morris, G. , Berk, M. , Carvalho, A. F. , Maes, M. , Walker, A. J. , & Puri, B. K. (2018). Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases. Behavioural Brain Research, 341, 154–175. PubMed

Nepozitek, J. , Varga, Z. , Dostalova, S. , Perinova, P. , Keller, J. , Robinson, S. , Ibarburu, V. , Prihodova, I. , Bezdicek, O. , Ruzicka, E. , Sonka, K. , & Dusek, P. (2023). Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder. NPJ Parkinson's Disease, 9, 1–8. PubMed PMC

Ohlhauser, L. , Smart, C. M. , & Gawryluk, J. R. (2019). Tract‐based spatial statistics reveal lower white matter integrity specific to idiopathic rapid eye movement sleep behavior disorder as a proxy for prodromal Parkinson's disease. Journal of Parkinson's Disease, 9, 723–731. PubMed

Pereira, J. B. , Weintraub, D. , Chahine, L. , Aarsland, D. , Hansson, O. , & Westman, E. (2019). Cortical thinning in patients with REM sleep behavior disorder is associated with clinical progression. NPJ Parkinsons Disease, 5, 1–8. PubMed PMC

Postuma, R. B. , Berg, D. , Stern, M. , Poewe, W. , Olanow, C. W. , Oertel, W. , Obeso, J. , Marek, K. , Litvan, I. , Lang, A. E. , Halliday, G. , Goetz, C. G. , Gasser, T. , Dubois, B. , Chan, P. , Bloem, B. R. , Adler, C. H. , & Deuschl, G. (2015). MDS clinical diagnostic criteria for Parkinson's disease. Movement Disorders, 30, 1591–1601. PubMed

Postuma, R. B. , Iranzo, A. , Hu, M. , Högl, B. , Boeve, B. F. , Manni, R. , Oertel, W. H. , Arnulf, I. , Ferini‐Strambi, L. , Puligheddu, M. , Antelmi, E. , Cochen de Cock, V. , Arnaldi, D. , Mollenhauer, B. , Videnovic, A. , Sonka, K. , Jung, K. Y. , Kunz, D. , Dauvilliers, Y. , … Pelletier, A. (2019). Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: A multicentre study. Brain, 142, 744–759. PubMed PMC

Pyatigorskaya, N. , Gaurav, R. , Arnaldi, D. , Leu‐Semenescu, S. , Yahia‐Cherif, L. , Valabregue, R. , Vidailhet, M. , Arnulf, I. , & Lehéricy, S. (2017). Magnetic resonance imaging biomarkers to assess Substantia nigra damage in idiopathic rapid eye movement sleep behavior disorder. Sleep, 40, zsx149. PubMed

Ravanfar, P. , Loi, S. M. , Syeda, W. T. , van Rheenen, T. E. , Bush, A. I. , Desmond, P. , Cropley, V. L. , Lane, D. J. R. , Opazo, C. M. , Moffat, B. A. , Velakoulis, D. , & Pantelis, C. (2021). Systematic review: Quantitative susceptibility mapping (QSM) of brain iron profile in neurodegenerative diseases. Frontiers in Neuroscience, 15, 618435. PubMed PMC

Schwarz, S. T. , Mougin, O. , Xing, Y. , Blazejewska, A. , Bajaj, N. , Auer, D. P. , & Gowland, P. (2018). Parkinson's disease related signal change in the nigrosomes 1–5 and the substantia nigra using T2* weighted 7T MRI. NeuroImage Clinical, 19, 683–689. PubMed PMC

Shahmaei, V. , Faeghi, F. , Mohammadbeigi, A. , Hashemi, H. , & Ashrafi, F. (2019). Evaluation of iron deposition in brain basal ganglia of patients with Parkinson's disease using quantitative susceptibility mapping. European Journal of Radiology Open, 6, 169–174. PubMed PMC

Sprenger, F. S. , Stefanova, N. , Gelpi, E. , Seppi, K. , Navarro‐Otano, J. , Offner, F. , Vilas, D. , Valldeoriola, F. , Pont‐Sunyer, C. , Aldecoa, I. , Gaig, C. , Gines, A. , Cuatrecasas, M. , Högl, B. , Frauscher, B. , Iranzo, A. , Wenning, G. K. , Vogel, W. , Tolosa, E. , & Poewe, W. (2015). Enteric nervous system α‐synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology, 85, 1761–1768. PubMed PMC

Sun, J. , Lai, Z. , Ma, J. , Gao, L. , Chen, M. , Chen, J. , Fang, J. , Fan, Y. , Bao, Y. , Zhang, D. , Chan, P. , Yang, Q. , Ye, C. , Wu, T. , & Ma, T. (2020). Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder. Movement Disorders, 35, 478–485. PubMed

Sung, Y. H. , Noh, Y. , & Kim, E. Y. (2021). Early‐stage Parkinson's disease: Abnormal nigrosome 1 and 2 revealed by a voxelwise analysis of neuromelanin‐sensitive MRI. Human Brain Mapping, 42, 2823–2832. PubMed PMC

Takahashi, H. , Watanabe, Y. , Tanaka, H. , Mihara, M. , Mochizuki, H. , Liu, T. , Wang, Y. , & Tomiyama, N. (2018). Quantifying changes in nigrosomes using quantitative susceptibility mapping and neuromelanin imaging for the diagnosis of early‐stage Parkinson's disease. The British Journal of Radiology, 91, 20180037. PubMed PMC

Thomas, G. E. C. , Zarkali, A. , Ryten, M. , Shmueli, K. , Gil‐Martinez, A. L. , Leyland, L. A. , McColgan, P. , Acosta‐Cabronero, J. , Lees, A. J. , & Weil, R. S. (2021). Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease. Brain, 144, 1787–1798. PubMed PMC

Tzourio‐Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single‐subject brain. Neuroimage, 15, 273‐289. PubMed

Uchida, Y. , Kan, H. , Sakurai, K. , Arai, N. , Kato, D. , Kawashima, S. , Ueki, Y. , & Matsukawa, N. (2019). Voxel‐based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment. Movement Disorders, 34, 1164–1173. PubMed

Uchida, Y. , Kan, H. , Sakurai, K. , Inui, S. , Kobayashi, S. , Akagawa, Y. , Shibuya, K. , Ueki, Y. , & Matsukawa, N. (2020). Magnetic susceptibility associates with dopaminergic deficits and cognition in Parkinson's disease. Movement Disorders, 35, 1396–1405. PubMed

Visser, M. , Marinus, J. , Stiggelbout, A. M. , & Van Hilten, J. J. (2004). Assessment of autonomic dysfunction in Parkinson's disease: The SCOPA‐AUT. Movement Disorder, 19, 1306–1312. PubMed

Vogel, D. , Shah, A. , Coste, J. , Lemaire, J. J. , Wårdell, K. , & Hemm, S. (2020). Anatomical brain structures normalization for deep brain stimulation in movement disorders. NeuroImage Clinical, 27, 102271. PubMed PMC

Xu, J. , Xiao, C. , Song, W. , Cui, X. , Pan, M. , Wang, Q. , Feng, Y. , & Xu, Y. (2021). Elevated heme oxygenase‐1 correlates with increased brain iron deposition measured by quantitative susceptibility mapping and decreased hemoglobin in patients with Parkinson's disease. Frontiers in Aging Neuroscience, 13, 656626. PubMed PMC

Yang, L. , Cheng, Y. , Sun, Y. , Xuan, Y. , Niu, J. , Guan, J. , Rong, Y. , Jia, Y. , Zhuang, Z. , Yan, G. , & Wu, R. (2022). Combined application of quantitative susceptibility mapping and diffusion kurtosis imaging techniques to investigate the effect of iron deposition on microstructural changes in the brain in Parkinson's disease. Frontiers in Aging Neuroscience, 14, 792778. PubMed PMC

Yu, X. , Li, W. , Ma, Y. , Tossell, K. , Harris, J. J. , Harding, E. C. , Ba, W. , Miracca, G. , Wang, D. , Li, L. , Guo, J. , Chen, M. , Li, Y. , Yustos, R. , Vyssotski, A. L. , Burdakov, D. , Yang, Q. , Dong, H. , Franks, N. P. , & Wisden, W. (2019). GABA and glutamate neurons in the VTA regulate sleep and wakefulness. Nature Neuroscience, 22, 106–119. PubMed PMC

Zhang, X. , Chai, C. , Ghassaban, K. , Ye, J. , Huang, Y. , Zhang, T. , Wu, W. , Zhu, J. , Zhang, X. , Haacke, E. M. , Wang, Z. , Xue, R. , & Xia, S. (2021). Assessing brain iron and volume of subcortical nuclei in idiopathic rapid eye movement sleep behavior disorder. Sleep, 44, zsab131. PubMed

Zhao, Y. , Qu, H. , Wang, W. , Liu, J. , Pan, Y. , Li, Z. , Xu, G. , & Hu, C. (2022). Assessing mild cognitive impairment in Parkinson's disease by magnetic resonance quantitative susceptibility mapping combined voxel‐wise and radiomic analysis. European Neurology, 85, 280–290. PubMed

Zhao, Y.‐N. , Jiang, J. B. , Tao, S. Y. , Zhang, Y. , Chen, Z. K. , Qu, W. M. , Huang, Z. L. , & Yang, S. R. (2022). GABAergic neurons in the rostromedial tegmental nucleus are essential for rapid eye movement sleep suppression. Nature Communications, 13, 7552. PubMed PMC