18F-AV1451 PET imaging and multimodal MRI changes in progressive supranuclear palsy

Nicolas Nicastro,Franklin I Aigbirhio,John T O’Brien,Luca Passamonti,William Richard Bevan-Jones,James B Rowe,P Simon Jones,Patricia Vazquez Rodriguez,Maura Malpetti

doi:10.1007/s00415-019-09566-9

Abstract

ObjectivesProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter (GM) of deep nuclei and cerebellum. We examined the relationship between tau pathology (assessed via 18F-AV1451 PET) and multimodal MRI imaging using GM volume, cortical thickness (CTh), and diffusion tensor imaging (DTI).MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3 T brain MRI including DTI. Twenty-one patients also had 18F-AV1451 PET imaging. Voxelwise volume-based morphometry, surface-based morphometry, and DTI correlations were performed with 18F-AV1451 binding in typical PSP regions of interest (putamen, thalamus and dentate cerebellum). Clinical impairment was also assessed in relation to the different imaging modalities.ResultsPSP subjects showed GM volume loss in frontotemporal regions, basal ganglia, midbrain, and cerebellum (FDR-corrected p < 0.05), reduced CTh in the left entorhinal and fusiform gyrus (p < 0.001) as well as DTI changes in the corpus callosum, internal capsule, and superior longitudinal fasciculus (FWE-corrected p < 0.05). In PSP, higher 18F-AV1451 binding correlated with GM volume loss in frontal regions, DTI changes in motor tracts, and cortical thinning in parietooccipital areas. Cognitive impairment was related to decreased GM volume in frontotemporal regions, thalamus and pallidum, as well as DTI alteration in corpus callosum and cingulum.ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and grey and white matter degeneration in PSP. This adds to the present literature about the complex interplay between structural changes and protein deposition.

Highlights

Progressive supranuclear palsy (PSP) encompasses a broad spectrum of motor, cognitive, and behavioural impairments
Using multimodal MRI imaging with volume-based morphometry (VBM), SBM and diffusion tensor imaging (DTI), we demonstrate that higher 18F-AV1451 binding in tau-prone regions affected by PSP was correlated with changes in grey and white matter
In comparing PSP patients with controls independently of 18F-AV1451 binding, extensive structural impairment was observed, with grey matter (GM) volume loss affecting frontotemporal regions, basal ganglia, midbrain and cerebellum, cortical thickness (CTh) reduction in left entorhinal and fusiform gyri, and DTI changes in the corpus callosum, internal capsule, corona radiata, and posterior thalamic radiations, among others. These results are in keeping with the previous observations [12,13,14, 17, 18], suggesting a key role of grey and white matter changes in the pathophysiology of PSP, especially the PSP-Richardson syndrome [26]

Summary

Introduction

Progressive supranuclear palsy (PSP) encompasses a broad spectrum of motor, cognitive, and behavioural impairments. These include akinesia, postural instability with early falls, John T. 18F-AV1451 binding is consistently increased in the basal ganglia, thalamus, and dentate cerebellum in patients with PSP relative to controls [5,6,7], mirroring its neuropathological distribution [4]. Albeit 18FAV1451 affinity for tau inclusions in non-AD tauopathies is less than in AD [8,9,10] and is not specific to tau [11], the distribution of 18F-AV1451 shows distinctive features in PSP [6]. Where high clinic-pathological correlations indicate likely PSP tau pathology, 18F-AV1451 can be used to quantify it and compare to other disease processes such as white matter pathology

Objectives

Methods

Results

Conclusion