利用超分辨率核磁共振成像和离子束显微镜对人类多巴胺能神经元中的铁进行原位磁测量

IF 11.6 1区 物理与天体物理 Q1 PHYSICS, MULTIDISCIPLINARY Physical Review X Pub Date : 2024-06-10 DOI:10.1103/physrevx.14.021041
Malte Brammerloh, Renat Sibgatulin, Karl-Heinz Herrmann, Markus Morawski, Tilo Reinert, Carsten Jäger, Roland Müller, Gerald Falkenberg, Dennis Brückner, Kerrin J. Pine, Andreas Deistung, Valerij G. Kiselev, Jürgen R. Reichenbach, Nikolaus Weiskopf, Evgeniya Kirilina
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引用次数: 0

摘要

顺磁性过渡金属在各种细胞催化过程中作为辅助因子发挥着至关重要的作用。然而,它们在反应性氧化状态下的高浓度会诱发氧化应激,导致细胞功能障碍或死亡。因此,拥有监测细胞中金属浓度和顺磁性能的方法对于医学和细胞生物学来说至关重要。在这里,我们提出了一种新颖的多模式细胞内磁力测量方法,无需事先分离,可在室温下直接测量组织中单个细胞内的金属磁性。通过检测细胞周围的微观磁场扰动,在 9.4 T 下使用超分辨率磁共振成像(MRI)显微镜测量单个细胞的磁矩。使用离子束显微镜或同步加速器微 X 射线荧光对相同细胞的细胞金属含量进行量化。然后根据细胞磁矩与细胞金属含量的斜率关系得出 9.4 T 时的金属磁感应强度。为了估算较低磁场下的磁感应强度,我们采用了多场磁共振弛豫测量法和生物物理模型,将 9.4 T 的磁感应强度值外推至低至 3 T 的磁场。测得神经络氨酸中铁的易感性为χρ=(2.98±0.19)×10-6 m3/kg,为了解多巴胺能神经元内铁的生物化学提供了独特的见解。所获得的值揭示了神经髓鞘内一个主要的单原子低亲和性铁结合位点,表明铁的神经毒性比以前认为的要高。此外,所测得的易感度值还确定了细胞铁浓度与铁敏感磁共振成像参数之间的定量关系,这种关系可以在体内进行无创测量。这一突破为在体内检测多巴胺能神经元密度和铁负荷铺平了道路,只需要一台标准的临床磁共振成像扫描仪。它有望促进帕金森病的早期诊断。总之,我们提出的新方法能够以高灵敏度直接测量单细胞内顺磁性金属的磁特性,并在宏观体积内测量大细胞群的磁特性,从而提供有关金属的细胞生物学的宝贵信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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In Situ Magnetometry of Iron in Human Dopaminergic Neurons Using Superresolution MRI and Ion-Beam Microscopy
Paramagnetic transition metals play a crucial role as cofactors in various cellular catalytic processes. However, their high concentrations in reactive oxidation states can induce oxidative stress, resulting in cell dysfunction or death. Hence, it is vital to have methods to monitor metal concentrations and paramagnetic properties in cells for medicine and cell biology. Here we present a novel multimodal method for in-cell magnetometry enabling direct measurement of metal magnetic properties within individual cells in tissue, without prior isolation and at room temperature. Individual cell magnetic moments are measured using superresolution magnetic resonance imaging (MRI) microscopy at 9.4 T by detecting microscopic magnetic-field perturbations around the cells. The cellular metal content is quantified using ion-beam microscopy or synchrotron micro-x-ray fluorescence for the same cells. The metal magnetic susceptibility at 9.4 T is then obtained from the slope of the cell magnetic moments’ dependence on cell metal content. To estimate the susceptibility at lower fields, multifield MR relaxometry and biophysical modeling are employed, extrapolating the 9.4-T susceptibility values to fields as low as 3 T. We apply the new method to determine the susceptibility of iron accumulated in human dopaminergic neurons inside neuromelanin, the by-product of dopamine synthesis. The susceptibility of iron in neuromelanin is measured to be χρ=(2.98±0.19)×106m3/kg providing unique insights into the biochemistry of iron inside dopaminergic neurons. The obtained value reveals a predominant monoatomic low-affinity iron-binding site within neuromelanin, indicating a higher neurotoxicity of iron than previously suggested. Furthermore, the measured susceptibility value establishes a quantitative relationship between cellular iron concentration and iron-sensitive MRI parameters, which can be noninvasively measured in vivo. This breakthrough paves the way for the in vivo detection of dopaminergic neuron density and iron load, requiring a standard clinical MRI scanner only. It promises to facilitate early diagnosis of Parkinson’s disease. In conclusion, our presented novel method enables the direct measurements of magnetic properties of paramagnetic metals within single cells with high sensitivity and across large cell groups within a macroscopic volume, providing invaluable information about the cellular biology of metals.
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来源期刊
Physical Review X
Physical Review X PHYSICS, MULTIDISCIPLINARY-
CiteScore
24.60
自引率
1.60%
发文量
197
审稿时长
3 months
期刊介绍: Physical Review X (PRX) stands as an exclusively online, fully open-access journal, emphasizing innovation, quality, and enduring impact in the scientific content it disseminates. Devoted to showcasing a curated selection of papers from pure, applied, and interdisciplinary physics, PRX aims to feature work with the potential to shape current and future research while leaving a lasting and profound impact in their respective fields. Encompassing the entire spectrum of physics subject areas, PRX places a special focus on groundbreaking interdisciplinary research with broad-reaching influence.
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