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Bech, M.

Publications and source records attributed to Bech, M..

3 recordsLinked to original sources

Quantitative MRI-based assessment of the ultrastructural compactness of myelin lamellae

Efficient neuronal communication relying on rapid saltatory conduction depends not only on the amount of myelin wrapping axons but also on myelin compact organisation. Yet, current quantitative MRI myelin imaging methods, such as Myelin Water Imaging (MWI) and quantitative Magnetization Transfer (qMT), are designed to estimate myelin content and are often treated as interchangeable, overlooking myelin organisation. We introduce Structural Myelin Integrity (SMI), a quantitative MRI metric designed to distinguish myelin compact organisation from content. SMI combines the distinct biophysical sensitivities of MWI and qMT to separate the water confined between myelin layers from the total myelin membrane mass. We evaluated SMI in two rodent models of myelin decompaction and one remyelination model, validating our findings with synchrotron small-angle X-ray scattering and electron microscopy. SMI detected myelin layers decompaction despite largely preserved myelin membranes, revealing structural abnormalities that were not explained by myelin content alone. During remyelination, SMI returned closer to healthy values at early timepoints than myelin-content metrics, consistent with the formation of thin-but-compact sheaths. These findings indicate that myelin content and organisation can dissociate and establish SMI as a non-invasive marker of myelin organisation, compatible with existing clinical MRI approaches for studying white matter changes not detected today.

neuroscience↗

Efficient murine cardiac phenotyping by combining synchrotron-based phase-contrast micro-CT, histology, immunofluorescence and spatial transcriptomics

1.Congenital heart disease is commonly studied using genetically modified mouse models, but characterization of complex three-dimensional (3D) cardiac anomalies remains technically challenging. Histology of fixed paraffin-embedded samples, typically used for structural and molecular analysis, is limited to two dimensions (2D). Synchrotron radiation-based phase-contrast micro-computed tomography (SRPC-{micro}CT) enables rapid, high-resolution, 3D imaging but had yet to be fully integrated with molecular tissue analysis. Importantly, SRPC-{micro}CT is nondestructive and compatible with paraffin-embedded tissue, potentially allowing integration with downstream molecular analyses such as multiplexed spatial transcriptomic profiling on tissue sections. Here, we present a pipeline combining SRPC-{micro}CT with complementary molecular approaches for rapid and accurate phenotyping of mouse hearts and for investigating disease mechanisms. We demonstrate the successful integration of high-resolution 3D imaging with spatial transcriptomics, fluorescent stainings, and histochemistry. Notably, all 2D modalities were applied sequentially to a single tissue section and registered within the 3D volume. This multimodal framework provides a powerful approach for linking structural and molecular information that is broadly applicable across biomedical research.

developmental biology↗

Axon morphology is modulated by the local environment and impacts the non-invasive investigation of its structure-function relationship

Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Non-invasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires 3D validation. Here, high resolution, 3D synchrotron X-ray Nano-Holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variance in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.

neuroscience↗