Affiliations: [a] ISR-Lisboa/LARSyS and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| [b] Neurological Imaging Department, Hospital de Santa Maria – CHULN, Lisbon, Portugal
| [c] Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [d] Department of Neuroscience and Mental Health, Neurology, Hospital de Santa Maria – CHULN, Lisbon, Portugal
| [e] CNS – Campus Neurológico Sénior, Torres Vedras, Portugal
| [f] Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [g] Imaging University Clinic, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Correspondence to: Rita G. Nunes, PhD, Institute for Systems and Robotics, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal. Tel.: +351 218418277; E-mail: [email protected].
Note:  These authors contributed equally to this work.
Abstract: Background:Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder inducing motor, psychiatric changes and cognitive decline, characterized pathologically by striatal atrophy. Pathological changes in the extra-striatal structures, such as the substantia nigra (SN), and abnormalities in pre-synaptic striatal dopamine neurotransmission are also known to occur. Neuromelanin (NM)-sensitive magnetic resonance imaging (NM-MRI) is an innovative technique that was recently developed allowing the in vivo study of pathological changes in the dopaminergic neurons of the SN. Objective:To investigate the SN MR signal in HD patients. Methods:We performed a cross-sectional study using a specific T1-weighted MR sequence to visualize NM. The areas and signal intensity contrast ratios of the T1 hyperintense SN regions were obtained using a semi-automatic segmentation method. Results:A total of 8 HD patients and 12 healthy subjects were evaluated. The SN area was markedly reduced in the HD group compared with the control group (p = 0.02), even after normalization of the SN area with the midbrain area and age correction (p = 0.01). There was a significant reduction in the intensity contrast ratio of the hyperintense SN areas to crus cerebri in HD patients comparing with controls (p = 0.04) after correction for age. Conclusions:NM-sensitive MR techniques were used for the first time to study the SN in HD patients, showing loss of NM in this region, supporting the implication of dopaminergic neuronal changes in disease pathology. Future research needs to be conducted to evaluate the potential of SN area and intensity contrast as biomarkers for HD.
Keywords: Huntington’s disease, neuromelanin-sensitive magnetic resonance imaging, neurodegeneration, substantia nigra