Abstract #1974

Microglial activation is accompanied by diffuse axonal loss in multiple sclerosis: in vivo evidence by multimodal 11C-PBR28 MR-PET and multi-shell diffusion imaging

Elena Herranz^1,2, Silvia De Santis ³, Constantina Andrada Treaba^1,2, Tobias Granberg^1,2,4,5, Russell Ouellette¹, Jacob Sloane^2,6, Eric Klawiter^1,2,7, Nicola Toschi⁸, and Caterina Mainero^1,2

¹Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³CSIC-UMH, Instituto de Neurociencias de Alicante, Alicante, Spain, ⁴Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden, ⁵Department of Radiology, Karolinska University Hospital, Stockholm, Sweden, ⁶Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁷Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁸Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

Neuropathological studies of multiple sclerosis (MS) established that diffuse microglia activation with axonal loss in the normal appearing white matter (NAWM) is a main determinant of disease progression. The in vivo study of neuroinflammation and axonal integrity is still challenging. We combined 11C-PBR28 MR-PET with multi-shell diffusion imaging to investigate neuroinflammation and microstructural abnormalities in the NAWM of MS subjects. Results showed evidence of diffuse neuroinflammation accompanied by microstructural diffusion abnormalities with decreased axonal density. The axonal density estimate from the Composite Hindered and Restricted Model of Diffusion was more sensitive than diffusion tensor imaging measures in disclosing axonal damage.

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