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| Home > Publications database > Mapping Primate Brain Rusting:Iron Accumulation in Dopaminergic Neurons across the Lifespan Studied by Quantitative MRI and X-ray Fluorescence |
| Home > Publications database > Mapping Primate Brain Rusting:Iron Accumulation in Dopaminergic Neurons across the Lifespan Studied by Quantitative MRI and X-ray Fluorescence |
| Master Thesis | PUBDB-2024-06287 |
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2023
Abstract: Pathological iron accumulation in the brain is a hallmark of several neurodegenerative diseases like Parkinson’s, Alzheimer’s and Huntington’s disease. Magnetic resonance imaging offers a unique non-invasive method to measure brain iron because iron affects the spin relaxation parameters of water protons and magnetic susceptibility of the brain tissue. Recently, it has been shown that iron accumulation in dopaminergic neurons in the human substantia nigra can be measured by quantitative MRI.The biophysical model linking the transverse relaxation rates R2 and R2∗ in the human substantia nigra to neuronal density and cellular iron load has been developed and validated in post mortem human brain tissue samples. However, these experiments were conducted on tissue from elderly donors and the mechanisms of iron-driven contrast in MRI have not yet been explored in younger individuals.Herein, we extended the previously proposed biophysical model of MRI contrast induced by DNs to the entire hominoid lifespan and validated the model using ultra-high resolution quantitative R2∗ maps acquired on a 7T scanner. Chimpanzees, being our closest relatives, are the most promising animal model for the human dopaminergic system.We acquired qMRI data from post mortem chimpanzee brains collected in an ethically and ecologically sustainable pipeline. The increase in overall R2∗ and in R2∗ contrast within the substantia nigra across the lifespan reflected iron accumulation in the substantia nigra.For the first time, we quantified the iron accumulation in individual DNs across the entire lifespan of chimpanzees using X-ray fluorescence. The iron concentration in neuromelanin clusters increased from 50(14) μg/g at birth to 440(220) μg/g at age
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