Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson’s Disease

Article type: Research Article

Authors: Fabbri, Margherita^{a; 1} | Reimão, Sofia^{a; b; 1} | Carvalho, Miguel^c | Nunes, Rita G.^{c; d} | Abreu, Daisy^a | Guedes, Leonor Correia^{a; e} | Bouça, Raquel^a | Lobo, Patricia P.^a | Godinho, Catarina^{a; f; g} | Coelho, Miguel^{a; e} | Gonçalves, Nilza C.^a | Rosa, Mario Miguel^{a; e} | Antonini, Angelo^h | Ferreira, Joaquim J.^{a; g; i; *}

Affiliations: [a] Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal | [b] Department of Neurological Imaging, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal | [c] Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, University of Lisbon, Lisbon, Portugal | [d] Department of Bioengineering and Institute for Systems and Robotics (LARSyS), Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal | [e] Department of Neurosciences, Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal | [f] Center for Interdisciplinary Research Egas Moniz(CiiEM), Instituto Superior de Ciências da Saúde EgasMoniz, Monte de Caparica, Portugal | [g] CNS – Campus Neurológico Sénior, Torres Vedras, Portugal | [h] Fondazione Ospedale San Camillo”-I.R.C.C.S., Parkinson and Movement Disorders Unit, Venice, Italy | [i] Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

Correspondence: [*] Correspondence to: Joaquim J Ferreira, MD, PhD, Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal. Tel.: +351 21 7802120; Fax: +351 21 7802129; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson’s disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. Objective:to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages. Methods:A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2–5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods. Results:13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2–5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2–5 year PD. NM signal area significantly correlated with HY (R = –0.37; P < 0.05) and Movement disorder Society Unified Parkinson’s Disease Rating Scale part II (MDS-UPDRS) (R = –0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = –0.26; P: 0.1). Conclusion:SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients.

Keywords: Neuromelanin, Parkinson’s disease, late-stage, disease progression, biomarker

DOI: 10.3233/JPD-171135

Journal: Journal of Parkinson's Disease, vol. 7, no. 3, pp. 491-501, 2017