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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},
}