Comparison of 18F-florbetaben quantification results using the standard Centiloid, MR-based, and MR-less CapAIBL® approaches: Validation against histopathology

Vincent Doré; Santiago Bullich; Christopher C Rowe; Pierrick Bourgeat; Salamata Konate; Osama Sabri; Andrew W Stephens; Henryk Barthel; Jurgen Fripp; Colin L Masters; Ludger Dinkelborg; Olivier Salvado; Victor L Villemagne; Susan De Santi

doi:10.1016/j.jalz.2019.02.005

Comparison of ¹⁸F-florbetaben quantification results using the standard Centiloid, MR-based, and MR-less CapAIBL^® approaches: Validation against histopathology

Alzheimers Dement. 2019 Jun;15(6):807-816. doi: 10.1016/j.jalz.2019.02.005. Epub 2019 May 14.

Authors

Affiliations

¹ Department of Molecular Imaging & Therapy, Austin Health, Melbourne, VIC, Australia; CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Brisbane, QLD, Australia. Electronic address: vincent.dore@csiro.au.
² Life Molecular Imaging, GmbH, Berlin, Germany.
³ Department of Molecular Imaging & Therapy, Austin Health, Melbourne, VIC, Australia; Department of Medicine, Austin Health, The University of Melbourne, Melbourne, VIC, Australia.
⁴ CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Brisbane, QLD, Australia.
⁵ Department of Molecular Imaging & Therapy, Austin Health, Melbourne, VIC, Australia; CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Brisbane, QLD, Australia.
⁶ Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
⁷ The Florey Institute of Neurosciences and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
⁸ Life Molecular Imaging Inc, Boston, MA, USA.

PMID: 31101517
DOI: 10.1016/j.jalz.2019.02.005

Abstract

Introduction: ¹⁸F-florbetaben is currently approved for the visual rule out of β-amyloid (Aβ) pathology. It is also used for recruitment and as an outcome measure in therapeutic trials, requiring accurate and reproducible quantification of Aβ burden in the brain.

Methods: Data from eighty-eight subjects (52 male subjects, aged 79.8 ± 10.6 years) who underwent antemortem ¹⁸F-florbetaben positron emission tomography scan and magnetic resonance imaging less than a year before neuropathological assessment at autopsy were evaluated. Image analysis was performed using the standard Centiloid (CL) statistical parametric mapping approach and CapAIBL^®. Imaging results were compared against autopsy data.

Results: Against combined Bielschowsky silver staining and immunohistochemistry histopathological scores, statistical parametric mapping had 96% sensitivity, 96% specificity, and 95% accuracy, whereas magnetic resonance-less CapAIBL standardized uptake value ratio_{Whole Cerebellum} had 94% sensitivity, 96% specificity, and 95% accuracy. Based on the combined histopathological scores, a CL threshold band of 19 ± 7 CL was determined.

Discussion: Quantification of ¹⁸F-florbetaben positron emission tomography scans using magnetic resonance-based and magnetic resonance-less CapAIBL^® approaches showed high agreement, establishing a pathology-based threshold in CL.

Keywords: Alzheimer's disease; Centiloid; Dementia; Florbetaben; Histopathology; Positron emission tomography (PET); β-amyloid.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnostic imaging*
Alzheimer Disease / pathology
Amyloid beta-Peptides / metabolism
Aniline Compounds*
Autopsy
Brain* / diagnostic imaging
Brain* / metabolism
Cerebellum / metabolism
Female
Humans
Image Processing, Computer-Assisted*
Magnetic Resonance Imaging*
Male
Middle Aged
Positron-Emission Tomography
Radiopharmaceuticals*
Sensitivity and Specificity
Stilbenes*

Substances

Amyloid beta-Peptides
Aniline Compounds
Radiopharmaceuticals
Stilbenes
4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene