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@INPROCEEDINGS{Calarco:1048412,
      author       = {Calarco, Navona and Progri, Skerdi and Kedo, Olga and
                      Kashyap, Sriranga and Lepage, Claude Y and Bludau, Sebastian
                      and Herold, Christina and Bernhardt, Boris and Evans, Alan C
                      and Amunts, Katrin and Uludağ, Kâmil},
      title        = {{B}ridging {S}cales to {M}ap the {H}uman {C}laustrum:
                      {B}ig{B}rain, {J}ulich, and 7-{T}esla {MRI}},
      reportid     = {FZJ-2025-04623},
      year         = {2025},
      abstract     = {Background. The claustrum is a thin, sheet-like grey matter
                      structure nestled between the putamen and insula, wrapped by
                      the capsulae externa and extrema. It is among the most
                      highly connected brain regions, with reciprocal projections
                      spanning the cortical mantle. But claustral function is
                      underinvestigated in living humans, as its complex
                      three-dimensional architecture is poorly understood, and its
                      thinness and proximity to neighboring structures challenge
                      the effective resolution of MRI. Consequently, few in vivo
                      studies exist, and those that do report radically
                      inconsistent characteristics—for example, volume estimates
                      differ by up to fivefold [FIG.1A]— raising concerns about
                      the reliability of findings on connectivity, function, and
                      case-control differences.Objective. To illuminate the
                      claustrum's three-dimensional anatomy and characterise
                      mapping challenges, our work establishes a multi-scale
                      reference linking micrometre histology to (sub)millimetre
                      MRI, quantifies resolution-dependent distortions and
                      inter-individual variability, and defines the practical
                      limits for reliable in vivo measurement.Methods. We manually
                      segmented the bilateral claustrum across three scales.
                      First, we derived a continuous three-dimensional
                      "gold-standard" reference from BigBrain (n=1; 100µm
                      isotropic, MNI ICBM-152 space) (Amunts et al. 2013)
                      [FIG.1B]. Second, in ten Julich postmortem brains (5 female;
                      37–85 years), we mapped the claustrum in native space on
                      every ~60th Merker-stained coronal section (1µm in-plane,
                      ~1.2mm spacing; >400 sections per brain) to validate
                      boundaries and assess population variability relative to
                      BigBrain (Amunts et al. 2020). Finally, we quantitatively
                      compared three 7-Tesla MP2RAGE datasets (n=30; 10 per
                      resolution at 0.5mm, 0.7mm, 1.0mm isotropic) with the
                      BigBrain reference and its resolution-matched downsamplings
                      to benchmark MRI's capacity to resolve claustral
                      morphology.Results. The BigBrain gold standard provides the
                      first continuous three-dimensional model of the human
                      claustrum from histology. It is broadly consonant with prior
                      two-dimensional histological descriptions but resolves the
                      claustrum in greater detail than recent three-dimensional
                      post-mortem MRI references (Coates and Zaretskaya 2024;
                      Mauri et al. 2024) and whole-brain anatomical atlases (Mai
                      et al. 2015; Ding et al. 2016). Comparison of BigBrain with
                      Julich brains confirmed that while the gold standard is
                      broadly representative, cellular-level resolution suggests
                      direct abutment with the olfactory tubercle, amygdaloid
                      complex (Kedo et al. 2018), and piriform cortex (Kedo et al.
                      2024) [FIG.1C], with substantial intersubject variability in
                      the ventral claustrum. MRI-to-BigBrain comparisons revealed
                      resolution-dependent distortions that scaled with voxel size
                      (1.0mm > 0.7mm > 0.5mm): mediolateral thickness was
                      inflated, producing paradoxical volume overestimation;
                      anteroposterior length was truncated with anterior portions
                      often missing; and superoinferior extent was underestimated
                      due to largely unresolved ventral "puddles"
                      [FIG.1D].Discussion. This work resolves a critical
                      methodological bottleneck in claustrum research by providing
                      the first comprehensive validation framework linking
                      histology to MRI. By leveraging BigBrain's unmatched
                      three-dimensional continuity alongside cellular-level
                      validation in the Julich brains, our findings establish
                      minimum resolution requirements and morphological benchmarks
                      for reliable in vivo measurement. In particular,
                      submillimeter resolution at ultra-high field consistently
                      recovers the claustrum’s dorsal core and achieves over
                      $50\%$ spatial agreement with the gold standard,
                      establishing a satisfactory foundation for in vivo studies
                      that may test long-standing hypotheses about claustral
                      connectivity, function, and clinical relevance.},
      month         = {Oct},
      date          = {2025-10-27},
      organization  = {9th BigBrain Workshop -HIBALL Closing
                       Symposium, Berlin (Germany), 27 Oct
                       2025 - 29 Oct 2025},
      subtyp        = {After Call},
      cin          = {INM-1},
      cid          = {I:(DE-Juel1)INM-1-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/1048412},
}