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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2014

Open Access 01-12-2014 | Research

Diagnostic effectiveness of quantitative [18F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus

Authors: Ville Leinonen, Juha O Rinne, Dean F Wong, David A Wolk, John Q Trojanowski, Paul F Sherwin, Adrian Smith, Kerstin Heurling, Mandy Su, Igor D Grachev

Published in: Acta Neuropathologica Communications | Issue 1/2014

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Abstract

Introduction

PET imaging of amyloid-β (Aβ) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer’s disease (AD) and mild cognitive impairment. AD-like Aβ pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting or intracranial pressure monitoring underwent [18F]flutemetamol PET before (N = 28) or after (N = 22) surgery. Cortical uptake of [18F]flutemetamol was assessed visually by blinded reviewers, and also quantitatively via standard uptake value ratio (SUVR) in specific neocortical regions in relation to either cerebellum or pons reference region: the cerebral cortex of (prospective studies) or surrounding (retrospective studies) the biopsy site, the contralateral homolog, and a calculated composite brain measure. Aβ pathology in the biopsy specimen (standard of truth [SoT]) was measured using Bielschowsky silver and thioflavin S plaque scores, percentage area of grey matter positive for monoclonal antibody to Aβ (4G8), and overall pathology impression. We set out to find (1) which pair(s) of PET SUVR and pathology SoT endpoints matched best, (2) whether quantitative measures of [18F]flutemetamol PET were better for predicting the pathology outcome than blinded image examination (BIE), and (3) whether there was a better match between PET image findings in retrospective vs. prospective studies.

Results

Of the 24 possible endpoint/SoT combinations, the one with composite-cerebellum SUVR and SoT based on overall pathology had the highest Youden index (1.000), receiver operating characteristic area under the curve (1.000), sensitivity (1.000), specificity (1.000), and sum of sensitivity and specificity for the pooled data as well as for the retrospective and prospective studies separately (2.00, for all 3). The BIE sum of sensitivity and specificity, comparable to that for quantitation, was highest using Bielschowsky silver as SoT for all SUVRs (ipsilateral, contralateral, and composite, for both reference regions). The composite SUVR had a 100% positive predictive value (both reference regions) for the overall pathology diagnosis. All SUVRs had a 100% negative predictive value for the Bielschowsky silver result.

Conclusion

Bielschowsky silver stain and overall pathology judgment showed the strongest associations with imaging results.
Appendix
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Metadata
Title
Diagnostic effectiveness of quantitative [18F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus
Authors
Ville Leinonen
Juha O Rinne
Dean F Wong
David A Wolk
John Q Trojanowski
Paul F Sherwin
Adrian Smith
Kerstin Heurling
Mandy Su
Igor D Grachev
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/2051-5960-2-46

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