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@ARTICLE{Sidorov:283220,
      author       = {Sidorov, Iulia and Ogrinc, Nina and Spieth, Lena and
                      Kopcil, Michal and Heijink, Marieke and Dalebout, Hans and
                      Saher, Gesine and Berghoff, Stefan A and Siuzdak, Gary and
                      Giera, Martin},
      title        = {{I}n-{S}ource {F}ragmentation {A}nnotation in {S}terol
                      {M}ass {S}pectrometry {I}maging.},
      journal      = {Analytical chemistry},
      volume       = {98},
      number       = {1},
      issn         = {0003-2700},
      address      = {Columbus, Ohio},
      publisher    = {American Chemical Society},
      reportid     = {DZNE-2026-00069},
      pages        = {509 - 518},
      year         = {2026},
      abstract     = {Spatial biology has emerged as a pivotal area in many life
                      science fields, with mass spectrometry imaging (MSI)
                      becoming a cornerstone for molecular imaging. Among recent
                      advancements to increase sensitivity, MALDI-2 technology has
                      significantly expanded the molecular space accessible to
                      MSI, increasing the ion yields of neutral metabolites, such
                      as sterols. Sterols have recently taken center stage in
                      numerous (patho-) physiological processes, including
                      neurodegenerative diseases that have attracted significant
                      scientific interest. However, in-source fragmentation (ISF)
                      poses a substantial challenge for accurate biological
                      interpretation of mass spectrometric data. In this study, we
                      observed and investigated the ISF of cholesterol during MSI
                      under MALDI and MALDI-2 conditions. Using a murine
                      intervention model, we demonstrate how ISF can compromise
                      the accuracy of biological interpretations, potentially
                      leading to significant misinterpretations. Our study
                      underscores the critical need to address ISF to ensure
                      accurate molecular annotation, particularly through tandem
                      mass spectrometry of in-source fragments. This is especially
                      important when using MALDI-2 techniques. Furthermore, we
                      introduce a high-resolution (5 μm) MSI technique, enabling
                      the precise spatial analysis of cholesterol distribution.},
      keywords     = {Animals / Spectrometry, Mass, Matrix-Assisted Laser
                      Desorption-Ionization: methods / Mice / Cholesterol:
                      analysis / Cholesterol: metabolism / Sterols: analysis /
                      Sterols: chemistry / Molecular Imaging: methods /
                      Cholesterol (NLM Chemicals) / Sterols (NLM Chemicals)},
      cin          = {AG Simons},
      ddc          = {540},
      cid          = {I:(DE-2719)1110008},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41408757},
      doi          = {10.1021/acs.analchem.5c05199},
      url          = {https://pub.dzne.de/record/283220},
}