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Disruption of neurite morphology parallels MS progression
Barbara Spanò1, Giovanni Giulietti1, Valerio Pisani1
1Neuroimaging Laboratory (B.S., G.G., M.B., M.C.), Santa Lucia Foundation, IRCCS; Department of Clinical and Behavioural Neurology (V.P., U.N., C.C.), Santa Lucia Foundation, IRCCS; Neurovascular Diagnosis Unit (M.M.), Department of Medical and Surgical Sciences and Biotechnology, Section of Neurology, Sapienza, University of Rome; Department of Neurology and Psychiatry (M.M., A.F.), Multiple Sclerosis Center, Sapienza, University of Rome, Italy; High Field Magnetic Resonance (E.T.), Max Planck Institute for Biological Cybernetics, Tuebingen, Germany; Department of System Medicine (U.N., C.C.), University of Rome "Tor Vergata," Italy; and Department of Neuroscience (M.B., M.C.), Brighton & Sussex Medical School, Falmer, United Kingdom.
Objectives:
To apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability.
Methods:
A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques.
Results:
Patients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas (p < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (p < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS.
Conclusions:
NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.
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