Age-Dependent Brain Neuroimaging Signatures in Nonhuman Primates
Poster No:
1016
Submission Type:
Abstract Submission
Authors:
Byeong Yeul Lee1, Joseph Laux1, Gabriella Worwa1, Yu Cong1, Jennifer Sword1, Marcelo Castro1, Venkatesh Mani1, Claudia Calcagno1
Institutions:
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, Frederick, MD
First Author:
Byeong Yeul Lee
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Co-Author(s):
Joseph Laux
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Gabriella Worwa
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Yu Cong
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Jennifer Sword
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Marcelo Castro
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Venkatesh Mani
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Claudia Calcagno
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases
Frederick, MD
Introduction:
Nonhuman primates (NHPs), particularly rhesus monkeys (RMs), are essential for medical and scientific research due to their close physiological, neuroanatomical, developmental, and cognitive similarities to humans (Roelfsema & Treue, 2014). However, a comprehensive understanding of the intricate neurodevelopmental trajectories in these animals remains elusive. This study investigates microstructural brain properties in RMs using a quantitative neuroimaging approach, incorporating T1 and T2* relaxation mapping and voxel-based morphometry (VBM).
Methods:
Magnetic resonance imaging (MRI) scans were conducted on 100 RMs (36 females and 54 males; mean age = 6.04 ± 2.22 y; age range = 1.96–10.3 y) using a Philips Achieva 3 Tesla scanner. Animals were intubated, immobilized with isoflurane, and positioned supine during imaging. High-resolution 3-dimensional T1 and T2* maps were acquired (in-plane resolution = 0.5 mm × 0.5 mm; slice thickness = 1 mm) using a dual-flip-angle method, incorporating fast field echo (Castro et al., 2010; Deoni, 2007) and a principle of echo-shifting sequence (Chavhan et al., 2009; Tomogane et al., 2013), respectively.
Data processing employed a custom pipeline integrating advanced normalization tools and voxel-based statistical parametric mapping. Key steps included image alignment, skull removal, tissue segmentation (Cox, 1996), spatial normalization (Tustison et al., 2014), smoothing (full width at half maximum [FWHM] = 1.5 mm), and general linear modeling. Analyses were performed in NIMH Macaque Template (NMT)space, with linear regression models assessing age-dependent and sex-dependent correlations (Figs 1A and 2A). Young (<5 years) and young adult (≥5 years) cohorts were compared using analysis of covariance (ANCOVA; Figs 1C and 2C), accounting for sex as a covariate. Area under the curve (AUC) and statistical significance (p < 0.05 family-wise error (FWE), corrected) were reported, with cluster enhancement applied to improve sensitivity (Spisak et al., 2019).
Data processing employed a custom pipeline integrating advanced normalization tools and voxel-based statistical parametric mapping. Key steps included image alignment, skull removal, tissue segmentation (Cox, 1996), spatial normalization (Tustison et al., 2014), smoothing (full width at half maximum [FWHM] = 1.5 mm), and general linear modeling. Analyses were performed in NIMH Macaque Template (NMT)space, with linear regression models assessing age-dependent and sex-dependent correlations (Figs 1A and 2A). Young (<5 years) and young adult (≥5 years) cohorts were compared using analysis of covariance (ANCOVA; Figs 1C and 2C), accounting for sex as a covariate. Area under the curve (AUC) and statistical significance (p < 0.05 family-wise error (FWE), corrected) were reported, with cluster enhancement applied to improve sensitivity (Spisak et al., 2019).
Results:
Significant age correlations were observed across imaging modality (corrected p < 0.0001; Figs 1 and 2). Male RMs exhibited stronger correlations than females. T1 values increased with age, notably in the cerebellum and medulla (r > 0.52; Figs 1A–2B), while T2* decreased in the basal ganglia and motor cortex (r < -0.75). VBM analysis showed increased volume density with age in the motor cortex, thalamus, and superior corona radiata (r > 0.6; Figs 2A and 2B) and decreased density in the inferior temporal cortex and cerebellum (r < -0.63; Figs 2A and 2B). These patterns enabled accurate differentiation of young and young adult cohorts in T1 (AUC > 0.86; Figs 1C–1D), T2* (AUC > 0.85), and tissue density (AUC > 0.82; Figs 2C–2D).
Conclusions:
This study highlights age-dependent brain development patterns in young RMs, with observed T1, T2*, and morphometric changes reflecting dynamic processes, such as myelination (Lee et al., 2019), iron accumulation (Bartzokis et al., 1994), and structural remodeling. These findings emphasize the importance of age considerations in NHP brain research and provide a foundation for further studies to validate results and explore other NHP species, advancing our understanding of NHP and human brain development.
Lifespan Development:
Early life, Adolescence, Aging 2
Normal Brain Development: Fetus to Adolescence 1
Keywords:
Aging
MRI
STRUCTURAL MRI
Other - Nonhuman Primates
1|2Indicates the priority used for review
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Provide references using APA citation style.
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