18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis

Antonio Carotenuto,Alexander Hammers,Federico E Turkheimer,Steven C R Williams,Marios Politis,George Dervenoulas,Jane Mackewn,Zachary Chappell,Beniamino Giordano,Sotirios Polychronis,Heather Wilson,Eli Silber,Gennaro Pagano,Peter Brex,Mattia Veronese

doi:10.1007/s00259-019-04533-y

Abstract

PurposeWe evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [18F]florbetapir PET-MR imaging.MethodsWe included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [18F]florbetapir PET-MR and both a clinical and cognitive assessment. [18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70–90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling.Results[18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV70–90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26).ConclusionOur findings demonstrate that [18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

Highlights

Multiple Sclerosis (MS) usually presents with episodes of transient neurological deficits, called ‘relapses’ [1]
We demonstrated that [18F]florbetapir positron emission tomography (PET) is a valid tool to detect the pattern of demyelination in MS, with a comparable accuracy between SUV70–90 PET measure and the computational distribution volume ratio (DVR) analysis methods
Combining PET with advanced magnetic resonance imaging (MRI) techniques, we showed that myelin damage was correlated with microstructural white matter changes and lower perfusion rate, providing additional information

Summary

Introduction

Multiple Sclerosis (MS) usually presents with episodes of transient neurological deficits, called ‘relapses’ [1]. Diffusion tensor imaging enables us to detect microstructural tissue damages in brain regions [5, 6], whereas arterial spin labelling provides a quantitative measure of the cerebral blood flow. Radioligands developed to measure amyloid-β pathology in grey matter for Alzheimer’s disease, such as [11C]PIB, [18F]florbetaben and [18F]florbetapir [8,9,10] showed affinity for myelin protein. This is due to the fact that these stilbene and benzothiazole derivatives have a very flat structure, interacting with the secondary structure of myelin basic protein to the way they interact with amyloid [11, 12]. We compared SUV70–90 analyses with the DVR kinetic modelling to estimate the clinical applicability of PET imaging through simplified semi-quantitative PET measures

Materials and methods

Results

Discussion

Findings

Compliance with ethical standards