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@ARTICLE{Brammerloh:618779,
      author       = {Brammerloh, Malte and Sibgatulin, Renat and Herrmann,
                      Karl-Heinz and Morawski, Markus and Reinert, Tilo and
                      Jäger, Carsten and Müller, Roland and Falkenberg, Gerald
                      and Brückner, Dennis and Pine, Kerrin J. and Deistung,
                      Andreas and Kiselev, Valerij G. and Reichenbach, Jürgen R.
                      and Weiskopf, Nikolaus and Kirilina, Evgeniya},
      title        = {{I}n {S}itu {M}agnetometry of {I}ron in {H}uman
                      {D}opaminergic {N}eurons {U}sing {S}uperresolution {MRI} and
                      {I}on-{B}eam {M}icroscopy},
      journal      = {Physical review / X},
      volume       = {14},
      number       = {2},
      issn         = {2160-3308},
      address      = {College Park, Md.},
      publisher    = {APS},
      reportid     = {PUBDB-2024-07140},
      pages        = {021041},
      year         = {2024},
      abstract     = {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 $𝜒_𝜌$=(2.98±0.19) ×
                      10$^{−6}$  m$^3$/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.},
      cin          = {DOOR ; HAS-User / FS-PETRA-S},
      ddc          = {530},
      cid          = {I:(DE-H253)HAS-User-20120731 /
                      I:(DE-H253)FS-PETRA-S-20210408},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633) / 6G3 - PETRA III (DESY) (POF4-6G3)
                      / FS-Proposal: I-20211534 (I-20211534) / HMRI - Non-Invasive
                      In-Vivo Histology in Health and Disease Using Magnetic
                      Resonance Imaging (MRI) (616905) / NISCI - Antibodies
                      against Nogo-A to enhance plasticity, regeneration and
                      functional recovery after acute spinal cord injury, a
                      multicenter European clinical proof of concept trial
                      (681094) / DFG project G:(GEPRIS)313856816 - SPP 2041:
                      Computational Connectomics (313856816)},
      pid          = {G:(DE-HGF)POF4-633 / G:(DE-HGF)POF4-6G3 /
                      G:(DE-H253)I-20211534 / G:(EU-Grant)616905 /
                      G:(EU-Grant)681094 / G:(GEPRIS)313856816},
      experiment   = {EXP:(DE-H253)P-P06-20150101},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:001245219300001},
      doi          = {10.1103/PhysRevX.14.021041},
      url          = {https://bib-pubdb1.desy.de/record/618779},
}