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Quantitation of PET spatial extent as a potential adjunct to visual interpretation of [18F]flortaucipir imaging : TAU-SPEX

Coomans, Emma M. LU ; van Tol, Bastiaan ; Groot, Colin LU ; Smith, Ruben LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Pontecorvo, Michael J. ; Shcherbinin, Sergey ; Kennedy, Ian and Kotari, Vikas , et al. (2025) In European Journal of Nuclear Medicine and Molecular Imaging 52(13). p.5135-5149
Abstract

Purpose: Among visually Tau-PET-positive scans, large variation exists in the size of the visually tau-positive area. Here, we propose a metric quantifying the spatial extent of visual Tau-PET-positivity, termed “TAU-SPEX”, and evaluate associations with visual read status, neurofibrillary tangle (NFT) pathology at autopsy, and cognition. Methods: [18F]flortaucipir data from 1,645 participants (aged 71.9 ± 8.2 years, 50.3% females) from four cohorts were visually read as positive or negative. TAU-SPEX was calculated as the percentage of gray matter voxels with suprathreshold Tau-PET uptake (using a threshold identical to that used for visual reading) in a spatially unconstrained whole-brain mask. We additionally computed... (More)

Purpose: Among visually Tau-PET-positive scans, large variation exists in the size of the visually tau-positive area. Here, we propose a metric quantifying the spatial extent of visual Tau-PET-positivity, termed “TAU-SPEX”, and evaluate associations with visual read status, neurofibrillary tangle (NFT) pathology at autopsy, and cognition. Methods: [18F]flortaucipir data from 1,645 participants (aged 71.9 ± 8.2 years, 50.3% females) from four cohorts were visually read as positive or negative. TAU-SPEX was calculated as the percentage of gray matter voxels with suprathreshold Tau-PET uptake (using a threshold identical to that used for visual reading) in a spatially unconstrained whole-brain mask. We additionally computed Tau-PET SUVr in a whole-brain and temporal meta-region. We tested the performance of TAU-SPEX for distinguishing visually tau-negative from tau-positive participants and for distinguishing participants with and without NFT Braak-V/VI pathology at autopsy (n = 18), and tested associations of TAU-SPEX with concurrent and longitudinal cognition. The performance of TAU-SPEX was compared to SUVr. Results: TAU-SPEX demonstrated strong performance in distinguishing tau-negative from tau-positive participants (AUC: 0.97). Moreover, TAU-SPEX showed high accuracy, sensitivity, specificity, positive predictive value and negative predictive value (all > 0.90) for identifying tau-positive participants, and showed high sensitivity (87.5%) and specificity (100.0%) for identifying participants with NFT Braak-V/VI pathology. TAU-SPEX was moderately associated with concurrent (β=-0.36 [-0.29, -0.43], p < 0.001) and longitudinal (β=-0.19 [-0.15, -0.22], p < 0.001) cognition. Across analyses, TAU-SPEX generally outperformed SUVr. Conclusion: TAU-SPEX was strongly associated with visual read, NFT Braak-V/VI pathology and cognition, and might be useful in clinical settings as a potential adjunct to [18F]flortaucipir visual interpretation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Diagnosis, PET, Tau
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
52
issue
13
pages
15 pages
publisher
Springer
external identifiers
  • pmid:40481862
  • scopus:105007330878
ISSN
1619-7070
DOI
10.1007/s00259-025-07384-y
language
English
LU publication?
yes
id
010defc1-12eb-4aaa-9ab7-1ad0967ba9bd
date added to LUP
2026-01-08 10:50:22
date last changed
2026-01-09 03:21:03
@article{010defc1-12eb-4aaa-9ab7-1ad0967ba9bd,
  abstract     = {{<p>Purpose: Among visually Tau-PET-positive scans, large variation exists in the size of the visually tau-positive area. Here, we propose a metric quantifying the spatial extent of visual Tau-PET-positivity, termed “TAU-SPEX”, and evaluate associations with visual read status, neurofibrillary tangle (NFT) pathology at autopsy, and cognition. Methods: [<sup>18</sup>F]flortaucipir data from 1,645 participants (aged 71.9 ± 8.2 years, 50.3% females) from four cohorts were visually read as positive or negative. TAU-SPEX was calculated as the percentage of gray matter voxels with suprathreshold Tau-PET uptake (using a threshold identical to that used for visual reading) in a spatially unconstrained whole-brain mask. We additionally computed Tau-PET SUVr in a whole-brain and temporal meta-region. We tested the performance of TAU-SPEX for distinguishing visually tau-negative from tau-positive participants and for distinguishing participants with and without NFT Braak-V/VI pathology at autopsy (n = 18), and tested associations of TAU-SPEX with concurrent and longitudinal cognition. The performance of TAU-SPEX was compared to SUVr. Results: TAU-SPEX demonstrated strong performance in distinguishing tau-negative from tau-positive participants (AUC: 0.97). Moreover, TAU-SPEX showed high accuracy, sensitivity, specificity, positive predictive value and negative predictive value (all &gt; 0.90) for identifying tau-positive participants, and showed high sensitivity (87.5%) and specificity (100.0%) for identifying participants with NFT Braak-V/VI pathology. TAU-SPEX was moderately associated with concurrent (β=-0.36 [-0.29, -0.43], p &lt; 0.001) and longitudinal (β=-0.19 [-0.15, -0.22], p &lt; 0.001) cognition. Across analyses, TAU-SPEX generally outperformed SUVr. Conclusion: TAU-SPEX was strongly associated with visual read, NFT Braak-V/VI pathology and cognition, and might be useful in clinical settings as a potential adjunct to [<sup>18</sup>F]flortaucipir visual interpretation.</p>}},
  author       = {{Coomans, Emma M. and van Tol, Bastiaan and Groot, Colin and Smith, Ruben and Palmqvist, Sebastian and Stomrud, Erik and Pontecorvo, Michael J. and Shcherbinin, Sergey and Kennedy, Ian and Kotari, Vikas and van der Flier, Wiesje M. and Pijnenburg, Yolande A.L. and Mattsson-Carlgren, Niklas and Hansson, Oskar and van de Giessen, Elsmarieke and Ossenkoppele, Rik}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Diagnosis; PET; Tau}},
  language     = {{eng}},
  number       = {{13}},
  pages        = {{5135--5149}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Quantitation of PET spatial extent as a potential adjunct to visual interpretation of [<sup>18</sup>F]flortaucipir imaging : TAU-SPEX}},
  url          = {{http://dx.doi.org/10.1007/s00259-025-07384-y}},
  doi          = {{10.1007/s00259-025-07384-y}},
  volume       = {{52}},
  year         = {{2025}},
}