# Assessing activation in the human brain using ultra-high performance FDG functional PET to investigate neurodegenerative disorders

> **NIH NIH F30** · YALE UNIVERSITY · 2024 · $33,958

## Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Early diagnosis of AD and
AD-related dementias (ADRD) is crucial to both avoiding potentially harmful delays in medical care, and
stratifying patients for treatment and research studies. AD pathogenesis is associated with several biomarkers,
including brain deposition of amyloid-beta (Aß) plaques and hyperphosphorylated tau, classified by the A/T/N
framework. The “A” and “T” represent measures of Aß and tau, respectively. The “N” encompasses biomarkers
of neuronal injury and neurodegeneration, including neuronal activity. While reductions in neuronal activity are
associated with rapid cognitive decline in ADRD including amnestic AD, neuronal activity has not been
established as a sensitive biomarker for AD, possibly due to limitations on current neuroimaging techniques to
detect such changes early in disease course.
 Although 18F-flourodeoxyglucose (FDG) functional positron emission tomography (fPET) measurements
can directly quantify neuronal metabolism, the use of FDG-fPET has previously been discouraged by
inadequate spatial resolution and sensitivity. Addressing this limitation, the Carson lab and our collaborators
recently developed the NeuroEXPLORER (NX), a brain-dedicated PET imaging system with ultra-high
sensitivity that is tenfold greater than the current state-of-the-art, the High Resolution Research Tomography
(HRRT), with ultra-high resolution and continuous head-motion tracking.
 Leveraging the ultra-high performance (UHP) of the NX to measure visual-stimulation induced neuronal
activity using FDG-fPET could permit reliable measurements of metabolism in small brain regions. Further,
several studies have demonstrated olfactory dysfunction (OD) early along ADRD, and Parkinson’s disease
progression. However, olfactory impairments specific to AD, that may permit its early detection or distinction
from other diseases, have not yet been established. Thus, it is hypothesized that NX FDG-fPET will yield
measurements of small differences in olfactory-stimulation induced neuronal activity between ADRD and
cognitively normal subjects. Finally, it is hypothesized that NX FDG-fPET signals will be correlated, but
temporally and spatially distinguishable from functional magnetic resonance imaging (fMRI). Aim 1 of this study
will investigate the capability of the NX to measure dynamic changes in glucose metabolism in small brain
nuclei. Aim 2 will investigate the application of a novel paradigm, olfactory-stimulation FDG-fPET, to
investigating early neurodegeneration in ADRD. Both aims will compare NX FDG-fPET to fMRI.
 My research will set the groundwork for future studies evaluating metabolism and tau, using ultra-high
sensitivity and resolution, as AD biomarkers, while validating and extending tasks currently reliant on fMRI. The
rigorous research skills I will obtain throughout this study, in combination with my training plan and excellent
mentorship will prepare me to b...

## Key facts

- **NIH application ID:** 10900927
- **Project number:** 1F30AG087667-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Nikkita Khattar
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,958
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900927

## Citation

> US National Institutes of Health, RePORTER application 10900927, Assessing activation in the human brain using ultra-high performance FDG functional PET to investigate neurodegenerative disorders (1F30AG087667-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900927. Licensed CC0.

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