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

## TL;DR

This study introduces TAU-SPEX, a new metric to quantify the spatial extent of tau positivity in PET scans, which shows strong performance in identifying tau-positive cases and predicting cognitive decline.

## Contribution

The novel contribution is the development and validation of TAU-SPEX, a quantitative metric for tau PET imaging that improves on standard SUVr measures.

## Key findings

- TAU-SPEX achieved an AUC of 0.97 in distinguishing tau-negative from tau-positive participants.
- TAU-SPEX showed high sensitivity and specificity for identifying NFT Braak-V/VI pathology.
- TAU-SPEX was moderately associated with both concurrent and longitudinal cognitive decline.

## Abstract

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.

[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.

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.

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.

The online version contains supplementary material available at 10.1007/s00259-025-07384-y.