# Methods for Quantitative Neuroimaging of Tau Burden in Pre-symptomatic AD

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $533,405

## Abstract

Whereas amyloid deposition tends to occur broadly throughout cortical regions and with relatively uniform pattern
of progression over time, the distribution of tau is highly focal at the early stages of pathology and its propagation
to other regions demonstrates a more complex spatiotemporal evolution. In addition the relatively lower
abundance in brain of tau compared to amyloid imparts greater requirements for binding affinity and selectivity
of tau radiotracers. Although second generation tau tracers reported within the past few years appear to have
more favorable properties in this regard, all tau tracers studied to date have been reported to exhibit off-target
binding to various substrates that can confound the quantification and interpretation of imaging data.
The goal of this application is to develop innovative technologies that improve the quantification of tau PET
imaging and enhance its utility in both research and eventual clinical settings. To address the focal nature of tau
deposition especially at prodromal stages of disease, we propose a novel kernel-based reconstruction method
that uses structural MR images as prior information and incorporates motion correction to obtain images with
unprecedented spatial resolution, allowing improved localization and quantification of tau in small structures such
as the rhinal cortex and the locus coeruleus. To mitigate the effects of off-target binding, we propose a kinetic
analysis strategies to identify non-specific, tau-specific, and off-target components. We also propose modeling
tactics to estimate maps of cerebral perfusion and to complement measures of tau burden as an additional index
of brain function. Lastly, we propose deep learning strategies to gain new insights into the spreading of tau and
to predict this progression in individual subjects.

## Key facts

- **NIH application ID:** 11011183
- **Project number:** 7R01AG076153-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Georges El Fakhri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $533,405
- **Award type:** 7
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11011183

## Citation

> US National Institutes of Health, RePORTER application 11011183, Methods for Quantitative Neuroimaging of Tau Burden in Pre-symptomatic AD (7R01AG076153-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11011183. Licensed CC0.

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