Biology subjects

Birkl, C.

Publications and source records attributed to Birkl, C..

3 recordsLinked to original sources

bioRxiv2026

Beyond iron concentration: iron aggregation shapes quantitative MRI in the human brain

Aceruloplasminemia (ACP) is a rare neurodegenerative disorder characterized by extreme cerebral iron overload and a shift towards larger iron aggregates, providing a unique possibility to study how iron aggregation shapes MRI contrast in vivo. We introduce a clinically feasible, multi-parametric quantitative MRI (qMRI) framework that combines quantitative susceptibility mapping (QSM), [Formula], and R2 to disentangle changes in total iron concentration from alterations in iron aggregation and its spatial organization at the cellular scale. Our biophysical model links the microstructure sensitive [Formula] ratio and the slope of the susceptibility-relaxation relationship (iron) to iron aggregation size and distribution. In a 3T qMRI study of three patients with ACP and three matched controls, we observe a marked increase in [Formula] and a pronounced increase of the [Formula]-QSM slope (iron: controls 154.09 {+/-} 52.89 s-1ppm-1; patients 296.68 {+/-} 57.18 s-1ppm-1; p = 0.016), consistent with enhanced iron aggregation and altered spatial organization. Model-based decomposition of transverse relaxation indicates that up to approximately 40% of the observed R2* elevation in ACP is attributable to changes in iron distribution beyond increased iron concentration alone. These findings establish a robust, translational qMRI approach for quantitative in vivo assessment of iron aggregation, revealing microstructural drivers of iron-related neurodegeneration that extend beyond bulk iron load.

biophysics↗

bioRxiv2022

Changes in cellular ferritin distribution of human brain tissue during autolysis revealed using analytical electron microscopy

Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of the proteins involved in iron homeostasis. Here, we focus on ferritin - the primary iron storage protein of the brain. Though it is known that glial cells and neurons differ in their concentration of ferritin, the change in the number of iron-filled ferritin cores or their distribution between different cell types during autolysis has not been revealed yet. Here, we show the cellular and region-wide distribution of ferritin in the human brain using state-of-the-art analytical electron microscopy. We validated the concentration of iron-filled ferritin cores to the absolute iron concentration measured by quantitative MRI and inductively coupled plasma mass spectrometry. We show that ferritins lost iron from their cores with progressing autolysis whereas the overall iron concentrations were unaffected. Though the highest concentration of ferritins was found in glial cells, we found that as the total ferritin concentration increased in a patient, ferritin accumulated more in neurons than in glial cells. Collectively our findings point out the unique behaviour of neurons in storing iron during autolysis and explain the differences between the absolute iron concentrations and iron-filled ferritin in a cell-type-dependent fashion in the human brain. Significance statementBalance of the iron load of the brain is crucial to preventing neurodegenerative disorders. Our study establishes a relation between autolysis, iron, and ferritin in the human brain with emphasis on the role of different cells in ferritin storage. We demonstrate that the iron load of ferritins does not correlate with mean iron concentrations during autolysis. Neurons retain more iron-loaded ferritin than glial cells with increasing ferritin count, which may make neurons more susceptible and exacerbate neuronal loss during iron overload. Neurons are also depleted of iron-loaded ferritin cores faster than glial cells during autolysis, demonstrating their unique role in iron storage. This paves the way to understanding the respective roles of neurons and glial cells in preventing or promoting neurodegeneration.

neuroscience↗

bioRxiv2020

Myelin water imaging depends on white matter fiber orientation in the human brain

The multiexponential T2 decay of the magnetic resonance imaging (MRI) signal from cerebral white matter can be separated into short components sensitive to myelin water and long components related to intra- and extracellular water. In this study we investigated to what degree the myelin water fraction (MWF) depends on the angle between white matter fibers and the main magnetic filed. Maps of MWF were acquired using multi echo CPMG and GRASE sequences. The CPMG sequence was acquired with a TR of 1073 ms, 1500 ms and 2000 ms. The fiber orientation was mapped with diffusion tensor imaging. By angle-wise pooling the voxels across the brains white matter, an orientation dependent MWF curve was generated. We found that MWF varied between 25% and 35% across different fiber orientations. The orientation dependency of the MWF is characterized by a dipole-dipole interaction model. Furthermore, the selection of the TR influences the orientation dependent and global white matter MWF. White matter fiber orientation induces a strong systematic bias on the estimation of MWF. This finding has important implications for future research and the interpretation of MWI results in previously published studies.

biophysics↗