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Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal Intensity
Sudeepti Southekal1, Michael D Devous2, Ian Kennedy2
1Avid Radiopharmaceuticals, Inc. (a wholly owned subsidiary of Eli Lilly and Company), Philadelphia Pennsylvania southekal@avidrp.com.
Summary
A new PET imaging technique, PERSI, improves tau pathology detection in Alzheimer disease by using white matter reference regions. This method reduces variability and enhances diagnostic accuracy for evaluating new therapies.
Area of Science:
- Neuroimaging
- Nuclear Medicine
- Alzheimer Disease Research
Background:
- Positron Emission Tomography (PET) imaging of tau pathology in Alzheimer disease (AD) often utilizes reference regions for tracer uptake normalization.
- White matter reference regions offer reduced variability compared to cerebellar regions but are susceptible to partial-volume effects.
- Accurate normalization is crucial for reliable quantification of tau burden and disease staging.
Purpose of the Study:
- To introduce and validate a novel technique, Parametric Estimation of Reference Signal Intensity (PERSI), for flortaucipir F 18 PET imaging.
- To leverage white matter reference regions while mitigating partial-volume blurring effects for improved tracer normalization.
- To assess the performance of PERSI in terms of test-retest variability and diagnostic group separation.
Main Methods:
- PERSI was developed by fitting a bimodal Gaussian distribution to white matter voxel-intensity histograms to define reference signal intensity.
- Flortaucipir F 18 PET data from subjects with Alzheimer disease, mild cognitive impairment, and normal cognition were analyzed.
- Test-retest variability and cross-sectional/longitudinal group differences (Aβ-positive impaired vs. Aβ-negative normal) were compared between PERSI and conventional reference regions.
Main Results:
- PERSI demonstrated superior test-retest reproducibility (1.84%) compared to other evaluated reference regions.
- PERSI achieved enhanced group separation ability, with significant Cohen's d values for cross-sectional (9.45) and longitudinal (2.34) data.
- Minimal baseline standardized uptake value ratio (SUVr) variability and change in SUVr (ΔSUVr) were observed in control subjects using PERSI.
Conclusions:
- PERSI effectively reduces variability in flortaucipir F 18 PET imaging, enhancing discrimination between diagnostic groups.
- This technique offers more accurate disease staging and robust measurement of tau burden changes over time.
- PERSI holds promise for improving the evaluation of therapeutic interventions for Alzheimer disease.
