Exploring the role of brain iron across the lifespan

Iris Menu Organizer
NYU Langone Health
New York, NY 
United States
 
Bart Larsen Co Organizer
University of Minnesota
Minneapolis, MN 
United States
 
3078 
Symposium 
Iron is a vital metabolic cofactor for many core neurobiological processes including myelination, dendritogenesis, and neurotransmitter synthesis. Iron deficiency in early life impairs brain development, while iron overload in older adults can cause neurodegeneration, suggesting that a critical balance of iron is necessary for normal brain function throughout the lifespan. Several quantitative MRI methods are sensitive to brain iron including the transverse relaxation rate R2*, and quantitative susceptibility mapping (QSM). These techniques suggest that excess iron accumulation or loss is associated with various neurodevelopmental and neurodegenerative disorders. In healthy subjects, studies have demonstrated correlations between R2* or QSM of basal ganglia structures and various aspects of cognitive ability. However, the pathway linking iron and cognition is unclear, with potential mechanisms including the mediating role of metabolic processes and the function of dopamine in deep gray matter. This symposium will bring together world-leaders in the field to provide a comprehensive overview of the iron imaging findings across the human lifespan–from the fetus to late life. Dr. Möller will begin with an overview of iron biochemistry and state of the art in MRI-based iron imaging. Dr. Ji will present data from fetal and infant MRI to show how brain iron changes through pre- to post-natal development. Dr. Parr will focus on brain iron during the adolescent years, using multimodal imaging to link iron levels to the development of cortical neurotransmitter systems. Finally, Dr. Wang will present prospective epidemiological data linking brain iron content to health outcomes in aging.

Objective

1. Understand iron levels in the brain change across the lifespan from womb to late life.
2. Learn the relationship between MRI-derived iron measurements and cognitive and clinical outcomes.
3. Appreciate the underlying biological mechanisms behind neuroimaging assessments of iron, in conjunction with other imaging modalities like PET scans. 

Target Audience

This symposium on brain iron imaging across the lifespan aims to offer an in-depth understanding of recent advancements in the study of brain iron dynamics for professionals and researchers in neuroscience, neuroimaging, and related fields. Moreover, it also serves attendees from the wider OHBM community who are interested in exploring the practical applications of these advancements in their respective fields. 

Presentations

Iron Neurobiology and Insights from Neuroimaging

Iron is critical for neuronal functioning, is required for myelin formation and maintenance, and is linked to dopamine biochemistry, among other cellular functions. The ability to quantify specific iron forms in the living brain would open new avenues for diagnosis or therapeutic monitoring and provide insights into key factors involved in disease pathogenesis or iron accumulation and redistribution associated with aging and development. Therefore, there is a fundamental interest in non-invasive imaging techniques that allow assessment of brain tissue composition. Magnetic resonance imaging (MRI) provides indirect information on iron deposition through measurements of proton relaxation rates of water and magnetic susceptibility. We will discuss MRI methods for a characterization of iron with basic aspects of cerebral iron biology to promote synergies between neuroimaging and neurobiology. 

Presenter

Harald Möller, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, N/A 
Germany

Fetal to Infant Brain Iron Development and Its Impact on Neural Activity

As a pivotal factor in neural development, iron accumulates rapidly in the brain from the earliest stages of life. Our analyses leverage fetal and infant multi-echo fMRI data to estimate T2* and investigate iron accumulation in the human brain from prenatal gestational age 20 weeks to postnatal 20 weeks. We will present data showing iron level changes spanning the perinatal period, and will delve into the challenges we encountered and the experiments we conducted to accurately estimate T2* from fetal fMRI data, which often involves significant motion artifacts. In addition, we will show how iron measures couple with neural activity through a cross-modality analysis in the context of early development. This study will be the first to chart the developmental trajectory of iron across the birth transition period. It will open new opportunities for exploring the role of iron in facilitating the emergence of early functional networks. 

Presenter

Lanxin Ji, NYU Langone Health New York, NY 
United States

Variation in striatal dopamine-related neurophysiology supports age-related modulation of prefrontal GABA/Glutamate balance in human adolescence

Changes in neurotransmitter systems, including glutamate, GABA, and dopamine (DA), during adolescence are thought to reflect critical period plasticity mechanisms that support the maturation of prefrontal cortex (PFC) – dependent cognition. Adolescent increases in DA may be a trigger for critical period plasticity, and animal models implicate DA in regulating developmental changes in PFC excitatory (glutamatergic) and inhibitory (GABAergic) balance, however this has not been tested in humans. To interrogate the role of DA in driving changes in PFC GABA/Glu balance, our analyses combine longitudinal 7T T2*-based estimates of striatal tissue iron as a metric of striatal DA-related neurophysiology and magnetic resonance spectroscopic imaging (MRSI) indices of prefrontal GABA/Glu in adolescents and young adults (10-32 years old at baseline). We will present novel, in vivo evidence showing that tissue iron, reflecting DA-related neurophysiology, supports developmental trajectories in PFC GABA/Glu balance, providing support for a model whereby developmental increases in DA are involved in fine-tuning GABA/Glu, and thus excitatory/inhibitory balance, across adolescence. Understanding developmental mechanisms underlying regulation of excitatory/inhibitory transmission can inform psychopathologies, i.e., schizophrenia, that emerge during adolescence and involve changes in DA, GABA, and Glu.  

Presenter

Ashley Parr, University of Pittsburgh Pittsburgh, PA 
United States

Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging

A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron. Here I present an open resource of QSM-based imaging measures of multiple brain structures in 35,885 subjects (45-82 years old) from the UK Biobank prospective epidemiological study. We identify phenotypic associations of magnetic susceptibility that include body iron, disease, diet, and alcohol consumption. Genome-wide associations relate magnetic susceptibility to genetic variants with biological functions involving iron, myelin, and extracellular matrix. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers world-wide, creating potential to discover novel, non-invasive markers of brain health. 

Presenter

Chaoyue Wang, Shanghai Jiao Tong University; University of Oxford Shanghai, N/A 
China