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In vivo assessment of myelin breakdown pattern in multiple sclerosis: a hybrid PET/MR [18F]florbetaben study
ECTRIMS Online Library. Carotenuto A. Oct 12, 2018; 232024
Antonio Carotenuto
Antonio Carotenuto
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Abstract: 271

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Remyelination in Multiple Sclerosis (MS) is a topic of increasing interest but reliable in vivo markers for myelin changes are needed. PET studies using selective amyloid-β targeting tracers might assess myelin pathology but a comparison with other advanced MRI techniques is still lacking.
We performed a hybrid PET-MR imaging study to evaluate pathological microstructural white matter damage in MS. Twelve relapsing-remitting MS patients and 12 healthy controls (HCs) underwent clinical assessments and a [18F]florbetaben PET/MR scan. [18F]florbetaben binding was quantified using both the Logan graphical reference to generate the distribution volume ratio (DVR) through a supervised cluster analysis and the standardized uptake value (SUV70-90). Fractional anisotropy, mean, axial and radial diffusivity were calculated from diffusion tensor imaging, whereas the cerebral blood perfusion was derived from arterial spin labelling data.
[18F]florbetaben DVR decreased in T2, T1, and T1 gadolinium enhancing lesions compared to HCs' white matter (-9.5%, -10.5% and -7.1%, respectively; P< 0.001) with a progressive reduction from normal-appearing white matter (NAWM) to lesion center (P< 0.001). The mean DVR in T2 lesions correlated with fractional anisotropy (coeff. = 0.313, P=0.003), mean, axial and radial diffusivity (coeff. £ -0.19, P=0.001). Mean cerebral perfusion was reduced in white matter tissue with reduced DVR compared to NAWM (-24%, P=0.001). T2 lesions' DVR correlated with EDSS (coeff. = -1.48), California verbal learning test (coeff. = 4.28), the brief visuo-spatial memory test (coeff. = 13.07), symbol digit modalities test (coeff. = 10.75) and the paced auditory serial addition test (coeff. = 6.27; all P< 0.001). DVR and SUV showed a comparable accuracy in differentiating NAWM from T2 lesions at ROC analysis (AUC 0.80 and 0.63, respectively; P=0.12).
We demonstrated an in-vivo a gradient of myelin loss from NAWM to MS lesions through a hybrid PET/MRI imaging. Myelin damages were associated with clinical markers of disease burden. [18F]florbetaben PET/MRI scan is a promising measure of myelination which might support clinicians in therapeutic decisions and allow the assessment the efficacy of newly developed drugs promoting remyelination.
Disclosure: Antonio Carotenuto, Beniamino Giordano, George Dervenoulas, Heather Wilson, Mattia Veronese, Zachary Chappell, Sotirios Polychronis, Flavia Niccolini, Jane MacKewn, Federico E. Turkheimer, Steven C.R. Williams and Alexander Hammers declare no potential conflicts of interest with respect to the research, authorship and/or publication of this abstract. Dr Eli Silber and Peter Brex received travel funding, research support and lecture from Biogen. Dr. Eli silber is the principal investigator and Dr. Peter A Brex is the sub-investigator for the anti-lingo study sponsored by Biogen. Professor Marios Politis' research is supported by Parkinson's UK, Lily and Edmond J. Safra Foundation, Michael J Fox Foundation (MJFF) for Parkinson's research, and CHDI Foundation.
Funding: This research was financially supported by Piramal Imaging (UK) Ltd. This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT 203148/Z/16/Z) and the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.

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