Longitudinal brain atlases of early developing cynomolgus macaques from birth to 48 months of age

Zhong, Tao; Wei, Jingkuan; Wu, Kunhua; Chen, Liangjun; Zhao, Fenqiang; Pei, Yuchen; Wang, Ya; Zhang, Hong-Jiang; Wu, Zhengwang; Huang, Ying; Li, Tengfei; Wang, Li; Chen, Yongchang; Ji, Weizhi; Li, Gang; Niu, Yuyu

doi:10.1016/j.neuroimage.2021.118799

Cited by 8 publications

(2 citation statements)

References 66 publications

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“…1x magnification tiled scans of the cynomolgus brains were first stitched using TeraStitcher then converted to Imaris image pyramid volumes using ImarisFileConverter. The 2x down sampled volume was then loaded and flipped along the y-axis to bring it into rough alignment with the T1 weighted template image for the 24-month-old cynomolgus atlas 80 . The brain volume was N4 corrected using a shrink factor of 32x, with 5 levels of correction and 50 iterations at each level.…”

Section: Cynomolgus Monkey Brain Atlas Registrationmentioning

confidence: 99%

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

Khoury,

Pizzo,

Discenza

et al. 2024

Preprint

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The blood-brain barrier (BBB) poses a significant challenge drug delivery to the brain. BBB-crossing molecules are emerging as a new class of therapeutics with significant potential for central nervous system (CNS) indications. In particular, transferrin receptor (TfR)- and CD98 heavy chain (CD98hc)-targeting molecules have been demonstrated to cross the BBB for enhanced brain delivery. Previously, we reported TfR and CD98hc antibody transport vehicles (ATVTfR and ATVCD98hc) that utilize these BBB receptors to improve CNS drug delivery1,2. Here, we provide a comprehensive and unbiased biodistribution characterization of ATVTfR and ATVCD98hc compared to a standard IgG at a multiscale level, ranging from whole-body to brain region- and cell type-targeting specificity. Mouse whole-body tissue clearing revealed distinct organ localization for each molecule. In the CNS, ATVTfR and ATVCD98hc not only achieves enhanced brain delivery but importantly, much broader parenchymal distribution in contrast to the severely limited distribution observed with a standard antibody that was not able to be improved even at very high dose levels. Using cell sorting and single-cell RNA sequencing of mouse brain, we revealed that standard IgG predominantly localizes to perivascular and leptomeningeal cells and reaches the CNS by entering the CSF, rather than crossing the BBB. In contrast, ATVTfR and ATVCD98hc enables broad parenchymal cell-specific distribution via transcytosis through brain endothelial cells (BECs) along the neurovasculature. Finally, we extended the translational relevance of our findings by revealing enhanced and broad brain and spinal cord biodistribution of ATVTfR compared to standard IgG in cynomolgus monkey. Taken together, this multiscale analysis reveals in-depth biodistribution differences between ATVTfR, ATVCD98hc, and standard IgG. These results may better inform platform selection for specific therapeutic targets of interest, optimally matching platforms to desired CNS target engagement, peripheral organ exposures, and predict or potentially reduce off-target effects.

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Section: Cynomolgus Monkey Brain Atlas Registrationmentioning

confidence: 99%

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

Khoury,

Pizzo,

Discenza

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Vertex-wise development analysis allows for the examination of cortical development at a highly localized level without reliance on predefined cortical parcellations, enabling the characterization of spatiotemporally fine-scale developmental patterns and providing fundamental insights into the regional specialization of the early developing brain ( 20 – 22 ). However, due to the difficulties in analyzing brain Magnetic Resonance (MR) images of early developing macaques, which typically exhibit extremely low tissue contrast and spatiotemporally heterogeneous imaging appearances as in human infants ( 23 – 25 ), our knowledge remains scarce on the vertex-wise developmental trajectories and spatial patterns of macaque cortical thickness and surface area during early postnatal stages.…”

mentioning

confidence: 99%

Longitudinal mapping of the development of cortical thickness and surface area in rhesus macaques during the first three years

Xia

Wang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Studying dynamic spatiotemporal patterns of early brain development in macaque monkeys is critical for understanding the cortical organization and evolution in humans, given the phylogenetic closeness between humans and macaques. However, due to huge challenges in the analysis of early brain Magnetic Resonance Imaging (MRI) data typically with extremely low contrast and dynamic imaging appearances, our knowledge of the early macaque cortical development remains scarce. To fill this critical gap, this paper characterizes the early developmental patterns of cortical thickness and surface area in rhesus macaques by leveraging advanced computing tools tailored for early developing brains based on a densely sampled longitudinal dataset with 140 rhesus macaque MRI scans seamlessly covering from birth to 36 mo of age. The average cortical thickness exhibits an inverted U-shaped trajectory with peak thickness at around 4.3 mo of age, which is remarkably in line with the age of peak thickness at 14 mo in humans, considering the around 3:1 age ratio of human to macaque. The total cortical surface area in macaques increases monotonically but with relatively lower expansions than in humans. The spatial distributions of thicker and thinner regions are quite consistent during development, with gyri having a thicker cortex than sulci. By 4 mo of age, over 81% of cortical vertices have reached their peaks in thickness, except for the insula and medial temporal cortices, while most cortical vertices keep expanding in surface area, except for the occipital cortex. These findings provide important insights into early brain development and evolution in primates.

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Collaborative Modality Generation and Tissue Segmentation for Early-Developing Macaque Brain MR Images

Wu,

Zhong,

Liang

et al. 2023

Lecture Notes in Computer Science

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Longitudinal brain atlases of early developing cynomolgus macaques from birth to 48 months of age

Cited by 8 publications

References 66 publications

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

Longitudinal mapping of the development of cortical thickness and surface area in rhesus macaques during the first three years

Collaborative Modality Generation and Tissue Segmentation for Early-Developing Macaque Brain MR Images

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