Imaging Studies Play a Pivotal Role in Elucidating the Pathophysiology of Parkinson Disease

HomeRadiologyVol. 311, No. 3 PreviousNext Reviews and CommentaryFree AccessEditorialImaging Studies Play a Pivotal Role in Elucidating the Pathophysiology of Parkinson DiseaseKei Yamada Kei Yamada Author AffiliationsFrom the Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan 602-8566.Address correspondence to the author (email: [email protected]).Kei Yamada Published Online:Jun 25 2024https://doi.org/10.1148/radiol.241285See also the article by Basaia et al in this issue.MoreSectionsPDF ToolsAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookXLinked In See also the article by Basaia et al in this issue.Dr Yamada received his MD from Kyoto Prefectural University of Medicine (KPUM) and did his fellowship training at University of Maryland, University of Rochester, and Harvard Medical School. He has served as professor and chair of KPUM, secretary general of the Asian-Oceanian Society of Neuroradiology and Head & Neck Radiology, president of the Japanese College of Radiology, and program chair of the International Society for Magnetic Resonance in Medicine.Download as PowerPointParkinson disease (PD) is not an uncommon condition: Almost everyone has one or two relatives or friends within their social circle who have this unsettling condition. However, our understanding of PD remains incomplete. This was even more true 40 years ago, when I was in medical school in Kyoto. Some of the few things we learned—or I should say, I remember learning at that time—about PD were that it is a neurodegenerative disease, it affects the central brain structures, and it is dopamine responsive.A few decades have passed since I was in medical school, and there has been a substantial gain in knowledge. Notable achievements in PD research arose from pathology studies, such as the work of Braak and colleagues (1). They showed that PD can be characterized by the presence of inclusion bodies containing aggregated α-synuclein. They also showed that progression of this PD pathology follows a specific pattern. It starts from the lower brainstem and anterior olfactory structures, slowly propagates rostrally, and eventually reaches the cerebral cortex. This observation led to the Braak staging model.It was later suggested that this orderly propagation of the pathology is induced by cell-to-cell transportation of the misfolded protein (2). This discovery was based on findings in young patients who had undergone transplant of fetal mesencephalic dopaminergic neurons (3). When their brains were dissected at autopsy, it was found that these transplanted cells had undergone degeneration secondary to α-synuclein deposition. This observation led to the theory that misfolded proteins have infectivity, leading to the "prion hypothesis."In this issue of Radiology, Basaia et al (4) try to elucidate whether the structural and functional architectures of the brain, as depicted with MRI, have any role in predicting the progression of cortical atrophy. In their prospective study conducted over a 3-year period, they evaluated two different cohorts: 60 healthy controls without any neurologic, psychiatric, or other disorders and 86 participants with mild PD. The healthy controls underwent diffusion tensor imaging and resting-state functional MRI to depict the structural and functional architectures of the brain. The data from the controls were used to generate a brain connectome. Patients with PD underwent three-dimensional T1-weighted MRI, and regional gray matter atrophy was calculated at baseline and every year for 3 years. The authors calculated partial correlations between structural and functional disease exposure (DE) indexes (indexes of disease pathology) at 1 or 2 years and atrophy progression at 2 or 3 years across gray matter regions. In addition, they applied feature selection models to predict atrophy over time.Basaia et al were successful in showing that there is indeed a correlation between the functional and structural organization of the brain and the pattern of cortical atrophy. DE indexes were correlated with gray matter atrophy progression at 2- and 3-year follow-up in patients with PD (r range, 0.22–0.33; P value range, .002–.04). Models including DE indexes, gray matter atrophy, and demographic and clinical variables were predictive of atrophy accumulation in some brain regions (R2 range, 0.40–0.61; P < .001).These results support the concept of staged progression of PD. It is noteworthy that this type of longitudinal observation is now possible using noninvasive imaging. There are a few apparent limitations of the study. First, gray matter atrophy is an indirect measure of neurodegeneration: Observations are limited to what can be captured using MRI. Second, this is a group analysis of a given cohort, and the findings cannot be applied to make decisions in individual cases.Nevertheless, I have no doubt that imaging studies will continue to play a pivotal role in investigating the pathophysiology of PD. There have been a number of other achievements in the past decades. For instance, a study of structural brain MRI scans showed that neuromelanin at the substantia nigra decreases as the disease progresses (5). Diffusion tensor imaging studies have shown microstructural damage to the nigrostriatal projection fibers (6), increased free water in the substantia nigra (7), and glymphatic dysfunction (8). Other studies have focused on functional aspects of PD. For instance, one study showed brain temperature alteration in PD, possibly reflecting neuroinflammation (9). Another study with MR spectroscopy showed impaired energy metabolism in the basal ganglia (10).These are just a fraction of the recent developments, and there is a lot more to learn from future studies. I would like to congratulate Basaia et al (4) for adding another discovery. I sincerely hope that these novel biomarkers will eventually lead to a deeper understanding of PD, which could potentially help researchers develop an effective disease-modifying therapy. Let us hope that we are coming one step closer to overcoming this devastating condition.Disclosures of conflicts of interest: K.Y. Board member of the Japan Radiological Society, Japanese College of Radiology, Kyoto College of Medical Science, and International Society for Magnetic Resonance in Medicine; editorial board member for Radiology, MAGMA, Korean Journal of Radiology, Japanese Journal of Radiology, The Neuroradiology Journal, and Investigative Magnetic Resonance Imaging; consultant or advisory role for the Asian-Oceanian Society of Neuroradiology and Head & Neck Radiology (secretary general) and Fujifilm Healthcare (consultant); and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Bracco, Eisai, GE HealthCare, GE HealthCare Pharma, Guerbet Japan, Kyowa Kirin, Mitsubishi Tanabe Pharma, Nihon Medi-Physics, Philips Healthcare, PDRadiopharma, Siemens Healthineers, Sanofi, Takeda Pharmaceuticals, Terumo, and United Imaging.Supported by the Japanese Ministry of Health, Labour, and Welfare and Doctor Net.References1. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24(2):197–211. MedlineGoogle Scholar2. Visanji NP, Brooks PL, Hazrati LN, Lang AE. The prion hypothesis in Parkinson's disease: Braak to the future. Acta Neuropathol Commun 2013;1(1):2. MedlineGoogle Scholar3. Li JY, Englund E, Holton JL, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008;14(5):501–503. MedlineGoogle Scholar4. Basaia S, Agosta F, Sarasso E, et al. Brain connectivity networks constructed using MRI for predicting patterns of atrophy progression in Parkinson disease. Radiology 2024;311(3):e232454. Google Scholar5. Matsuura K, Maeda M, Tabei KI, et al. A longitudinal study of neuromelanin-sensitive magnetic resonance imaging in Parkinson's disease. Neurosci Lett 2016;633:112–117. MedlineGoogle Scholar6. Yoshikawa K, Nakata Y, Yamada K, Nakagawa M. Early pathological changes in the parkinsonian brain demonstrated by diffusion tensor MRI. J Neurol Neurosurg Psychiatry 2004;75(3):481–484. MedlineGoogle Scholar7. Burciu RG, Ofori E, Archer DB, et al. Progression marker of Parkinson's disease: a 4-year multi-site imaging study. Brain 2017;140(8):2183–2192. MedlineGoogle Scholar8. Bae YJ, Kim JM, Choi BS, et al. Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space. Parkinsonism Relat Disord 2023;114:105767. MedlineGoogle Scholar9. Chen HL, Yamada K, Sakai K, Lu CH, Chen MH, Lin WC. Alteration of brain temperature and systemic inflammation in Parkinson's disease. Neurol Sci 2020;41(5):1267–1276. MedlineGoogle Scholar10. Prasuhn J, Schiefen T, Güber T, et al. Levodopa impairs the energy metabolism of the basal ganglia in vivo. Ann Neurol 2024;95(5):849–857. MedlineGoogle ScholarArticle HistoryReceived: Apr 30 2024Revision requested: May 6 2024Revision received: May 13 2024Accepted: May 13 2024Published online: June 25 2024 FiguresReferencesRelatedDetailsAccompanying This ArticleBrain Connectivity Networks Constructed Using MRI for Predicting Patterns of Atrophy Progression in Parkinson DiseaseJun 25 2024RadiologyRecommended Articles Using MRI to Identify Supranuclear Palsy from Parkinson Disease and Dementia with Lewy BodiesRadiology2019Volume: 293Issue: 3pp. 654-655Brain Connectivity Networks Constructed Using MRI for Predicting Patterns of Atrophy Progression in Parkinson DiseaseRadiology2024Volume: 311Issue: 3Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian SyndromesRadiology2021Volume: 300Issue: 2pp. 260-278Structural Brain Connectome and Cognitive Impairment in Parkinson DiseaseRadiology2016Volume: 283Issue: 2pp. 515-525The "Glymphatic" Window on Neurodegeneration in SynucleinopathiesRadiology2023Volume: 307Issue: 5See More RSNA Education Exhibits Shedding light on the Substantia Nigra: Anatomy, Function, Imaging Technique and Pathophysiology.Digital Posters2022Deep Brain Stimulation (DBS) - Pre and Post Operative Imaging, From Adequate Nucleus and Fiber Tract Localization to Electrode MisplacementDigital Posters2022Need-to-know Neuroimaging with Clinical Correlation: Parkinson's Disease and Related Movement DisordersDigital Posters2022 RSNA Case Collection Multiple System Atrophy (MSA)RSNA Case Collection2021NeuroferritinopathyRSNA Case Collection2021Non-accidental anoxic brain injury RSNA Case Collection2021 Vol. 311, No. 3 Metrics Altmetric Score PDF download