Boumezbeur, F. | Search bioRxiv

bioRxiv2026

An Ultra-High-Resolution 17.2 T MRI Atlas (HypoAtlas) and Multimodal Pipeline to Study the Mouse Hypothalamus: Sexual Dimorphism and Lateralization Insights

Structural and functional insights into the mouse hypothalamus are hampered by its small size and deep location. Here, we leverage ultra-high-field magnetic resonance imaging (UHF-MRI) at 17.2 Tesla to achieve unprecedented spatial resolution in structural, functional and neurochemical imaging of the mouse hypothalamus, including sexual dimorphism in certain nuclei. High-resolution ex vivo anatomical MRI enabled precise hypothalamic parcellation, improving on existing atlases and revealing nuclei previously unresolved by MRI. Diffusion MRI and tractography mapped intra- and extra-hypothalamic pathways, facilitating circuit-level exploration without a priori assumptions. Resting-state fMRI combined with independent component analysis identified novel hypothalamic networks, demonstrating the enhanced capacity of UHF MRI to detect deep-brain activity. {superscript 1}H-magnetic resonance spectroscopy quantified neurochemical profiles, revealing sexually dimorphic heterogeneity within the hypothalamus. Our comprehensive multimodal approach uncovers sex differences in hypothalamic anatomy, microstructure, and neurochemistry, emphasizing the importance of sex as a biological variable. This integrated pipeline offers a valuable resource for dissecting hypothalamic circuits and functions, advancing our understanding of neuroendocrine regulation, behavior, and disease mechanisms, with direct translational relevance.

neuroscience↗

bioRxiv2023

Characterization of early white matter changes in CADASIL using microscopic diffusion imaging and relaxometry

Background and purposeCerebral small vessel diseases (SVDs) are characterized by early white matter (WM) changes, whose pathological underpinnings are yet poorly understood. CADASIL is a monogenic and archetypal SVD, providing an ideal model for investigating these changes. Here, we used multicompartment microscopic diffusion imaging and relaxometry to elucidate microstructural changes underlying early WM abnormalities in CADASIL. MethodsWe acquired diffusion MRI data with a multiple-shell Q-space sampling strategy, and relaxometry T1 and T2 data, with a 160 and 80-m isotropic resolution respectively, ex vivo, in CADASIL and control mice. Diffusion datasets were computed with the Neurite Orientation Dispersion and Density Imaging model to extract the neurite density index, the extracellular free water and the orientation dispersion index. Relaxometry datasets were computed with a 3-compartment myelin water imaging model to extract the myelin content. MRI metrics were compared between CADASIL and control mice using voxel and WM tract-based analyses and with electron microscopy analysis. ResultsWM in CADASIL mice displayed a widespread reduction in general fractional anisotropy, a large increase in extracellular free water, a reduction in the myelin content, but no reduction in neurite density. Electron microscopy analysis showed a {bsim}2-fold increase in the extracellular spaces and an elevation of the g-ratio indicative of myelin sheath thinning in CADASIL WM. ConclusionOur findings suggest that accumulation of interstitial fluid and myelin damage are 2 major factors underlying early WM changes in CADASIL. Advanced diffusion MRI and relaxometry are promising approaches to decipher the underpinnings of WM alterations in SVDs.

neuroscience↗