Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies
Marta Lancione,
Graziella Donatelli,
Eleonora Del Prete,
Nicole Campese,
Daniela Frosini,
Matteo Cencini,
Mauro Costagli,
Laura Biagi,
Giacomo Lucchi,
Michela Tosetti,
Massimiliano Godani,
Dario Arnaldi,
Michele Terzaghi,
Federica Provini,
Claudio Pacchetti,
Pietro Cortelli,
Enrica Bonanni,
Roberto Ceravolo,
Mirco Cosottini
Affiliations
Marta Lancione
Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy; Imago7 Research Foundation, Pisa, Italy
Graziella Donatelli
Imago7 Research Foundation, Pisa, Italy; Neuroradiology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Corresponding author at: Neuroradiology Unit, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa 2, 56124 Pisa, Italy.
Eleonora Del Prete
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Nicole Campese
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Daniela Frosini
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Matteo Cencini
Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy; Imago7 Research Foundation, Pisa, Italy
Mauro Costagli
Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI), University of Genoa, Genoa, Italy
Laura Biagi
Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy; Imago7 Research Foundation, Pisa, Italy
Giacomo Lucchi
Neuroradiology Unit, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Michela Tosetti
Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy; Imago7 Research Foundation, Pisa, Italy
Massimiliano Godani
Neurology Unit, Sant'Andrea Hospital, La Spezia, Italy
Dario Arnaldi
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Michele Terzaghi
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; IRCCS Mondino Foundation, Pavia, Italy
Federica Provini
IRCCS Istituto delle Scienze Neurologiche di Bologna, Clinica Neurologica Rete Metropolitana, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
Claudio Pacchetti
Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
Pietro Cortelli
IRCCS Istituto delle Scienze Neurologiche di Bologna, Clinica Neurologica Rete Metropolitana, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
Enrica Bonanni
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Roberto Ceravolo
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Mirco Cosottini
Neuroradiology Unit, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.
