Regional Associations of Cortical Superficial Siderosis and β-Amyloid-Positron-Emission-Tomography Positivity in Patients With Cerebral Amyloid Angiopathy.

Anika Finze,Anika Finze,Frank Arne Wollenweber,Hannes Wahl,Cihan Catak,Katharina Buerger,Jennifer Linn,Sophia Stöcklein,Sophia Stöcklein,Matthias Brendel,Matthias Brendel,Matthias Brendel,Matthias Brendel,Axel Rominger,Axel Rominger,Daniel Janowitz,Peter Bartenstein,Peter Bartenstein,Peter Bartenstein

doi:10.3389/fnagi.2021.786143

Abstract

ObjectiveThis is a cross-sectional study to evaluate whether β-amyloid-(Aβ)-PET positivity and cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA) are regionally colocalized.MethodsTen patients with probable or possible CAA (73.3 ± 10.9 years, 40% women) underwent MRI examination with a gradient-echo-T2*-weighted-imaging sequence to detect cSS and 18F-florbetaben PET examination to detect fibrillar Aβ. In all cortical regions of the Hammers Atlas, cSS positivity (MRI: ITK-SNAP segmentation) and Aβ-PET positivity (PET: ≥ mean value + 2 standard deviations of 14 healthy controls) were defined. Regional agreement of cSS- and Aβ-PET positivity was evaluated. Aβ-PET quantification was compared between cSS-positive and corresponding contralateral cSS-negative atlas regions. Furthermore, the Aβ-PET quantification of cSS-positive regions was evaluated in voxels close to cSS and in direct cSS voxels.ResultscSS- and Aβ-PET positivity did not indicate similarity of their regional patterns, despite a minor association between the frequency of Aβ-positive patients and the frequency of cSS-positive patients within individual regions (rs = 0.277, p = 0.032). However, this association was driven by temporal regions lacking cSS- and Aβ-PET positivity. When analyzing all composite brain regions, Aβ-PET values in regions close to cSS were significantly higher than in regions directly affected with cSS (p < 0.0001). However, Aβ-PET values in regions close to cSS were not different when compared to corresponding contralateral cSS-negative regions (p = 0.603).ConclusionIn this cross-sectional study, cSS and Aβ-PET positivity did not show regional association in patients with CAA and deserve further exploitation in longitudinal designs. In clinical routine, a specific cross-sectional evaluation of Aβ-PET in cSS-positive regions is probably not useful for visual reading of Aβ-PETs in patients with CAA.

Highlights

MATERIALS AND METHODSCerebral amyloid angiopathy (CAA) is characterized by leptomeningeal and cortical beta-amyloid (Aβ) accumulation in small vessels (Vinters, 1987)
The patients presented themselves to the respective clinics with focal neurological symptoms
Of the four women (66.2 ± 14.4 years) and six men (78.0 ± 4.9 years), three patients were diagnosed with a possible CAA and seven patients with a probable CAA, according to the modified Boston criteria (Linn et al, 2010)

Summary

Introduction

MATERIALS AND METHODSCerebral amyloid angiopathy (CAA) is characterized by leptomeningeal and cortical beta-amyloid (Aβ) accumulation in small vessels (Vinters, 1987). The aforementioned findings suggest that there is a regional relationship between Aβ accumulation and cSS, and we aimed to test this hypothesis by in vivo imaging. In this regard, fibrillar Aβ is sufficiently detectable by FDA-approved PET tracers in living patients (Clark et al, 2011; Curtis et al, 2015; Sabri et al, 2015), and modern data analysis pipelines allow to investigate the PET and MRI data in matched spatial orientation (Wollenweber et al, 2014). We hypothesized that regionally pronounced Aβ accumulation leads to a colocalized increase of cSS due to higher vessel vulnerability in these regions This could facilitate improved judgment of Aβ-PET positivity by the specific analysis of cSS-positive brain regions. A detailed segmentation approach was used to investigate the regional agreement between fibrillar Aβ accumulation and cSS

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