Flortaucipir F 18 quantitation using parametric estimation of reference signal intensity.
Open accessAbstract
PET imaging of tau pathology in Alzheimer disease may benefit from the use of white matter reference regions. These regions have shown reduced variability compared with conventional cerebellar regions in amyloid imaging. However, they are susceptible to contamination from partial-volume blurring of tracer uptake in the cortex. We present a new technique, PERSI (Parametric Estimation of Reference Signal Intensity), for flortaucipir F 18 count normalization that leverages the advantages of white matter reference regions while mitigating potential partial-volume effects. Methods: Subjects with a clinical diagnosis of Alzheimer disease, mild cognitive impairment, or normal cognition underwent T1-weighted MRI and florbetapir imaging (to determine amyloid [Aβ] status) at screening and flortaucipir F 18 imaging at single or multiple time points. Flortaucipir F 18 images, acquired as 4 × 5 min frames 80 min after a 370-MBq injection, were motion-corrected, averaged, and transformed to Montreal Neurological Institute (MNI) space. The PERSI reference region was calculated for each scan by fitting a bimodal gaussian distribution to the voxel-intensity histogram within an atlas-based white matter region and using the center and width of the lower-intensity peak to identify the voxel intensities to be included. Four conventional reference regions were also evaluated: whole cerebellum, cerebellar gray matter, atlas-based white matter, and subject-specific white matter. SUVr (standardized uptake value ratio) was calculated for a statistically defined neocortical volume of interest. Performance was evaluated with respect to test–retest variability in a phase 2 study of 21 subjects (5–34 d between scans). Baseline variability in controls (SD of SUVr and ΔSUVr) and effect sizes for group differences (Cohen d; Aβ-positive impaired vs. Aβ-negative normal) were evaluated in another phase 2 study with cross-sectional data (n = 215) and longitudinal data (n = 142/215; 18 ± 2 mo between scans). Results: PERSI showed superior test–retest reproducibility (1.84%) and group separation ability (cross-sectional Cohen d = 9.45; longitudinal Cohen d = 2.34) compared with other reference regions. Baseline SUVr variability and ΔSUVr were minimal in Aβ control subjects with no specific flortaucipir F 18 uptake (SUVr, 1.0 ± 0.04; ΔSUVr, 0.0 ± 0.02). Conclusion: PERSI reduced variability while enhancing discrimination between diagnostic cohorts. Such improvements could lead to more accurate disease staging and robust measurements of changes in tau burden over time for the evaluation of putative therapies.
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Flortaucipir is being developed as a positron emission tomography tracer for detection of the aggregated tau of Alzheimer disease.
“Flortaucipir is being developed as a PET tracer for detection of the aggregated tau of AD.19,21,22,23,24”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [22]
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- Authors
- Southekal, S., Devous, M. D., Kennedy, I., Navitsky, M., Lu, M., Joshi, A. D., Pontecorvo, M. J., & Mintun, M. A.
- Affiliations
- Avid Radiopharmaceuticals (United States) (US)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2017-11-30
- Volume
- 59
- Issue
- 6
- Pages
- 944-951
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2771176174
- Cited by
- 92
- References
- 34
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 10 · 2023: 12 · 2022: 14 · 2021: 13 · 2020: 10 · 2019: 13 · 2018: 7 · 2017: 1
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Avid Radiopharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- tau PET, Persis, standardized uptake value ratio, test-retest reproducibility, Alzheimer's disease, mild cognitive impairment, amyloid status, florbetapir
- MeSH terms
- Aged, Alzheimer Disease, Carbolines, Female, Humans, Image Processing, Computer-Assisted, Male, Reference Standards, Positron-Emission Tomography
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