Aging & Longevity

Dynamic 18F-FDG PET characterizes age-related changes in fitted ventricular FDG kinetics in humans.

Zhou Z, Zhao T, et al. • Imaging neuroscience (Cambridge, Mass.) • 2026

TL;DR

Dynamic 18F-FDG PET can characterize ventricular tracer kinetics without intrathecal contrast administration, revealing a robust age-dependent decline in both tracer entry and removal processes and supporting its potential utility for studying ventricular CSF transport dynamics in aging and disease.

Key Findings

Results

Ventricular FDG kinetic parameter K1 (effective tracer entry) demonstrated a strong negative correlation with age.

Pearson correlation r = -0.700, p < 0.001
K1 describes effective tracer entry into the ventricular compartment
The correlation remained significant after multivariable adjustment for sex, ventricular volume, and depression severity
Data were derived from baseline dynamic 18F-FDG PET scans of participants with major depressive disorder enrolled in a prior clinical trial

Results

Ventricular FDG kinetic parameter k2 (net tracer removal) demonstrated a strong negative correlation with age.

Pearson correlation r = -0.712, p < 0.001
k2 describes net removal of tracer from the ventricular compartment
The correlation remained significant in multivariable models adjusting for sex, ventricular volume, and depression severity
k2 showed a stronger correlation with age than K1 (r = -0.712 vs. r = -0.700)

Results

Ventricular volume was a significant predictor of both K1 and k2 in multivariable regression models.

Ventricular volume was included as a covariate in multiple linear regression analyses alongside sex, age, and depression severity
Ventricular volume predicted both kinetic parameters independently of age
This finding suggests that ventricular size contributes to observed tracer kinetic dynamics beyond age effects alone

Results

Depression severity was a significant predictor of k2 (net tracer removal) but not K1 in multivariable models.

The study population consisted of participants with major depressive disorder from a prior clinical trial
Depression severity was assessed as a clinical covariate in multivariable regression
The association of depression severity with k2 but not K1 suggests differential sensitivity of the two kinetic parameters to clinical factors
This association was independent of age, sex, and ventricular volume

Methods

Time-activity curves from lateral ventricles were successfully modeled using a variant of the single-tissue compartment kinetic model to estimate ventricular CSF tracer dynamics.

The method did not require intrathecal contrast administration, relying solely on dynamic 18F-FDG PET data
Time-activity curves were extracted from the lateral ventricles
K1 and k2 were estimated as kinetic parameters describing tracer entry and net removal, respectively
The approach was applied to baseline dynamic PET data from a clinical trial cohort with major depressive disorder

Background

Dynamic 18F-FDG PET was proposed as a clinically accessible method for indirectly quantifying ventricular CSF transport, including potential glymphatic-associated transport pathways.

Ventricular CSF transport is described as 'an important component of intracranial solute movement' that 'may contribute to glymphatic-associated transport pathways'
Existing clinically accessible methods for quantifying ventricular CSF tracer dynamics in humans are described as 'limited'
The ventricular kinetic parameters were interpreted as indirect measures of CSF transport
The authors suggest the method has 'potential utility for studying ventricular CSF transport dynamics in aging and disease'

What This Means

This research suggests that a standard brain imaging technique called dynamic FDG-PET — commonly used in clinical and research settings — can be repurposed to measure how a tracer moves into and out of the fluid-filled spaces (ventricles) in the brain. Researchers extracted time-activity curves from the lateral ventricles of participants with major depressive disorder and used a mathematical model to estimate two kinetic parameters: how fast the tracer enters the ventricles (K1) and how fast it is removed (k2). Both parameters showed strong negative correlations with age, meaning older participants had significantly slower tracer movement in both directions. These findings held up even after accounting for sex, the size of the ventricles, and depression severity. The practical implication is that this approach could serve as a non-invasive, widely available way to study cerebrospinal fluid (CSF) transport in the brain — a process thought to be important for clearing waste products and potentially linked to the brain's glymphatic system. Currently, studying CSF dynamics typically requires injecting contrast agents directly into the spinal fluid, which is invasive and not routinely done. This method uses a radioactive glucose tracer that is already administered intravenously as part of standard PET scanning. This research also found that the size of the ventricles independently predicted both kinetic parameters, and that depression severity was associated specifically with the tracer removal rate (k2). These results suggest that ventricular FDG kinetics could be a useful biomarker for studying brain aging and possibly certain neuropsychiatric conditions, though further research in broader and healthier populations is needed to fully establish its clinical utility.

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Citation

Zhou Z, Zhao T, Wang H, Carretero Benites A, Gardus J, Wen Q, et al.. (2026). Dynamic 18F-FDG PET characterizes age-related changes in fitted ventricular FDG kinetics in humans.. Imaging neuroscience (Cambridge, Mass.). https://doi.org/10.1162/IMAG.a.1395

Key Findings

What This Means

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