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Submillimeter postmortem and in vivo diffusion and susceptibility magnetic resonance imaging to characterize cortical micro-and meso-structures

This study demonstrates that submillimeter-resolution postmortem and in vivo diffusion and susceptibility MRI metrics exhibit moderate correspondence in characterizing human cortical micro- and meso-structures, providing a comprehensive anatomical reference to bridge high-fidelity postmortem imaging with in vivo neuroimaging applications.

Original authors: Yuto Uchida, Hyeong-Geol Shin, Laura Gomez-Isaza, Juan Troncoso, Adnan Bibic, Julianna Gerold, Dongsuk Sung, Yohan Jun, Fuyixue Wang, Zijing Dong, Susie Huang, Berkin Bilgic, Peter van Zijl, Xu Li, Ke

Published 2026-06-30

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CC BY 4.0

Original authors: Yuto Uchida, Hyeong-Geol Shin, Laura Gomez-Isaza, Juan Troncoso, Adnan Bibic, Julianna Gerold, Dongsuk Sung, Yohan Jun, Fuyixue Wang, Zijing Dong, Susie Huang, Berkin Bilgic, Peter van Zijl, Xu Li, Kenichi Oishi

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

Imagine the human brain as a vast, incredibly complex city. For a long time, scientists have tried to map this city using MRI scanners, which act like satellite cameras taking pictures from space. However, these "satellite photos" are often a bit blurry, making it hard to see the tiny details of the neighborhoods (the cortex) where the real action happens.

This paper is like a team of cartographers trying to solve a specific puzzle: Can we see the same tiny details in a living person's brain as we can in a preserved brain sample?

Here is the story of how they tried to answer that, explained simply:

The Two Types of "Maps"

To understand the brain's tiny structures, the researchers used two different types of "cameras" (MRI techniques):

The "Traffic Flow" Camera (Diffusion MRI): This measures how water molecules move. Think of it like watching cars on a highway. If the cars are all driving in neat, straight lanes, the "traffic flow" is high. This helps scientists see how the brain's wiring is organized.
The "Magnetic Compass" Camera (Susceptibility MRI): This measures how magnetic the tissue is. Think of it like a compass that reacts to iron and other minerals hidden inside the brain cells. Different neighborhoods have different amounts of "magnetic dust," which changes how the compass points.

The Experiment: The "Perfect" vs. The "Real"

The researchers wanted to compare these cameras under two very different conditions:

The "Perfect" Lab (Postmortem): They took a preserved brain from a 71-year-old man. Because the brain was preserved and sitting still in a special container, they could take extremely high-resolution photos (about 0.5mm, which is like zooming in until you can see individual bricks). They could even rotate the brain 12 different times to get a perfect 3D view of the magnetic properties. This took about 52 hours of scanning time!
The "Real" World (In Vivo): They scanned a healthy 27-year-old woman while she was alive. To make it a fair comparison, they tried to use the exact same camera settings to get the same 0.5mm resolution. However, because she was alive, she had to breathe, her heart was beating, and she couldn't stay perfectly still for 52 hours. They had to finish in about 3 hours.

The Big Discovery: Do the Maps Match?

The team compared the "Perfect" maps and the "Real" maps to see if the patterns were the same.

The Good News: Even though the "Real" map was a bit blurrier and noisier (like a photo taken with a shaky hand), the general patterns matched surprisingly well.
- Both maps showed that the "motor control" areas (where you move your hands and legs) and the "back of the brain" areas had high "traffic flow" and high "magnetic dust."
- Both maps showed a unique area called the cingulate cortex that had high "traffic flow" but low "magnetic dust." This is like finding a neighborhood with busy streets but no iron deposits—a specific fingerprint of that area.
The Correlation: When they plotted the data, the two maps lined up with a moderate degree of accuracy (about 50-53%). This means that while the "Real" map isn't as sharp as the "Perfect" lab map, it still captures the essential layout of the brain's tiny structures.

Why the "Real" Map Wasn't Perfect

The paper explains a few reasons why the living scan looked a bit different:

The Shaky Hand: In the living scan, tiny movements (breathing, blood flow) created "static" or blur, making the edges of the neighborhoods less sharp.
The Time Crunch: The living scan had to be much faster, so the image had less "signal" (light) to work with.
The Preservative Effect: The brain in the lab was soaked in formalin (a preservative). This chemical changes the brain's texture slightly, kind of like how a dried-out sponge feels different from a fresh one. This might have made the "traffic flow" look slower in the lab sample than it actually is in a living brain.

The Bottom Line

This study is like a proof-of-concept that says: "Yes, we can see the brain's tiny neighborhoods in living people, and they look very similar to the ultra-detailed maps we get from preserved brains."

The researchers didn't claim this cures diseases or changes medical practice yet. Instead, they built a comprehensive reference guide. They showed that the "blurry" living photos are actually reliable enough to study the brain's micro-structure, bridging the gap between the ultra-detailed lab work and what we can see in a living patient.

Technical Summary: Submillimeter Postmortem and In Vivo Diffusion and Susceptibility MRI for Cortical Micro- and Meso-Structure Characterization

Problem Statement
The human cerebral cortex exhibits heterogeneous microstructural organization defined by cytoarchitecture, myelination, and tissue composition. While quantitative magnetic resonance imaging (MRI), specifically diffusion (sensitive to microstructural anisotropy) and susceptibility (sensitive to iron and myelin content), offers a noninvasive framework to map these features, achieving high-resolution, whole-cortical coverage in vivo remains challenging. Physiological noise, motion artifacts, and limited scan times restrict in vivo spatial resolution and signal-to-noise ratio (SNR). Conversely, postmortem MRI allows for prolonged acquisitions at submillimeter resolutions, providing high-fidelity anatomical references. However, a critical gap exists in translational neuroimaging: it remains unclear which fine-scale cortical patterns observed in optimized postmortem scans are preserved, attenuated, or redistributed in in vivo acquisitions at matched resolutions. Specifically, the correspondence between postmortem and in vivo fractional anisotropy (FA) and tissue magnetic susceptibility ( $\chi$ ) at the whole-cortex level has not been comprehensively quantified.

Methodology
The study employed a comparative, atlas-based approach using high-resolution MRI data from two distinct sources:

Postmortem Imaging: A left hemibrain from a 71-year-old male neurologically normal donor was scanned.
- Diffusion MRI: Acquired on a 3T Connectome 2.0 system using a segmented 3D EPI sequence (0.55 mm isotropic resolution). The scan utilized three b-value shells (3,000, 6,000, and 10,000 s/mm²) and took approximately 52 hours.
- Susceptibility MRI: Acquired on a 7T system using a multi-orientation 3D gradient-echo (GRE) sequence (0.5 mm isotropic resolution). To enable robust Quantitative Susceptibility Mapping (QSM) via the Calculation of Susceptibility through Multiple Orientation Sampling (COSMOS) method, the sample was scanned at 12 different orientations relative to the main magnetic field ( $B_0$ ). A custom 3D-printed ellipsoidal container with a rotatable base system facilitated controlled reorientation.
In Vivo Imaging: Data were acquired from a 27-year-old healthy female volunteer.
- Diffusion MRI: Acquired on the same 3T Connectome system using the Romer-EPTI sequence (0.5 mm isotropic resolution), taking approximately 3 hours.
- Susceptibility MRI: Acquired on a 7T system using a 3D GRE sequence (0.5 mm isotropic resolution) with 6 different head orientations relative to $B_0$ .
Data Processing and Analysis:
- Parcellation: The OpenMAP-T1 framework with the JHU–MNI (Eve) Level 4 atlas (144 regions) was applied to both datasets to extract region-wise metrics.
- Registration: Nonlinear warping was used for postmortem data to correct geometric distortions, while rigid registration was used for in vivo data to preserve native geometry.
- Quantification: Region-wise mean values of FA and $\chi$ were extracted. Linear (Pearson) and rank-based (Spearman) correlations were calculated to assess the correspondence between postmortem and in vivo metrics across cortical regions. Cortical surface mapping was used to visualize micro- and meso-structural heterogeneities.

Key Results

Spatial Patterns: Both postmortem and in vivo datasets revealed consistent anatomical variations. Elevated FA and $\chi$ values were observed in the precentral/postcentral and posterior cortical regions compared to surrounding association cortices. The cingulate cortex exhibited a distinct pattern of relatively high FA but low $\chi$ values.
Correlation: Region-wise comparisons of the left hemispheric cortical regions demonstrated moderate positive correlations between postmortem and in vivo metrics:
- FA: Pearson's $r = 0.52$ ( $p = 0.02$ ); Spearman's $\rho = 0.49$ ( $p = 0.03$ ).
- $\chi$ : Pearson's $r = 0.53$ ( $p = 0.01$ ); Spearman's $\rho = 0.39$ ( $p = 0.08$ , not significant).
Systematic Differences: Postmortem FA values were systematically lower than in vivo values across nearly all cortical regions. Postmortem maps exhibited greater spatial sharpness and tissue contrast, whereas in vivo maps showed localized blurring and reduced dynamic range, particularly in susceptibility maps near cortical surfaces.
Laminar Visualization: Postmortem maps clearly delineated laminar structures and fine-scale susceptibility variations across cortical layers. In vivo maps preserved laminar contrast in the precentral region but were limited by motion artifacts in posterior regions.

Significance and Claims
The authors claim that this study provides initial insight into how quantitative diffusion and susceptibility MRI contrast patterns translate from high-fidelity postmortem imaging to in vivo acquisitions. The findings suggest that while absolute values and spatial sharpness differ due to biological (fixation, age, sex) and technical (SNR, motion, temperature) factors, the relative inter-regional ordering of cortical microstructural patterns is largely preserved.

The study positions the combined submillimeter postmortem and in vivo dataset as a comprehensive anatomical reference for cortical microstructure mapping. It supports the use of postmortem multi-orientation acquisitions not only as a ground truth for histological correlation but also as a high-fidelity reference for validating and training emerging reconstruction methods (e.g., physics-informed deep learning) aimed at reducing orientation sampling requirements for in vivo susceptibility imaging. The authors conclude that these atlas-based analyses offer a translational bridge between postmortem imaging, in vivo MRI, and future histological validation in neurological research, though they explicitly note that the findings are based on a single donor and a single volunteer, limiting generalizability to population-level variations.

The Two Types of "Maps"

The Experiment: The "Perfect" vs. The "Real"

The Big Discovery: Do the Maps Match?

Why the "Real" Map Wasn't Perfect

The Bottom Line

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