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Sung, D.

Publications and source records attributed to Sung, D..

3 recordsLinked to original sources

A human subcortical connectome at 400 μm resolution

The fiber pathways of the human subcortex are of particular importance in clinical neuroscience, as they are targeted by neuromodulation therapies, such as deep brain stimulation (DBS) and lesion approaches, in various motor and psychiatric disorders. However, the complexity, size, and position of these pathways make them challenging to image non-invasively with diffusion MRI (dMRI). As a result, recent efforts in atlasing these pathways to guide neuromodulation have resorted to using synthetic data. Here we present the first extensive reconstruction of fiber pathways of the human subcortex with ultra-high-resolution dMRI. We leverage a unique, ex vivo dMRI dataset acquired by the BRAIN CONNECTS center for Large-scale Imaging of Neural Circuits (LINC) on the first-of-its-kind Connectome 2.0 scanner. Our contribution is two-fold. First, by showing the feasibility of reconstructing these pathways with non-invasive neuroimaging at the single subject level, we set the stage for future research into reconstructing them in vivo in individual patients. Second, we provide a high-definition atlas of basal-ganglia-thalamocortical circuits that is readily extensible via our publicly released data and annotations. As a first demonstration of its clinical validity, we align our atlas to "hotspots" from previous DBS studies and identify pathways associated with therapeutic or side effects.

neuroscience↗

Multi-dimensional diffusion MRI at ultra-high gradient strength for mapping axonal architecture and microstructure in the primate brain

We present the most comprehensive sampling of the macaque and human brain with diffusion MRI to date. As part of the BRAIN CONNECTS center for Large-scale Imaging of Neural Circuits, we leverage ultra-high-gradient MRI systems, including the first-of-its-kind Connectome 2.0, for post-mortem acquisitions. Each sample is imaged for [~]250 hours at multiple spatial resolutions down to 0.25 mm isotropic for whole macaque brains and 0.4 mm isotropic for human hemispheres. Our optimized protocols allow us to sample both species across [~]50 diffusion shells varying in b-value, diffusion time, and echo time, reaching ultra-high b-values up to 64000 s/mm2 with high signal-to-noise ratio. We demonstrate that these multi-dimensional data resolve not only white matter connectional architecture but also cortical and subcortical cytoarchitectonic boundaries, at a level of detail previously inaccessible in whole-brain noninvasive imaging. As such, these data are an important resource for both technical development and basic and clinical neuroscience.

neuroscience↗

A Suite of Mouse Reagents for Studying Amelogenesis

Amelogenesis, the formation of dental enamel, is driven by specialized epithelial cells called ameloblasts, which undergo successive stages of differentiation. Ameloblasts secrete enamel matrix proteins (EMPs), proteases, calcium, and phosphate ions in a stage-specific manner to form mature tooth enamel. Developmental defects in tooth enamel are common in humans, and they can greatly impact the well-being of affected individuals. Our understanding of amelogenesis and developmental pathologies is rooted in past studies using epithelial Cre driver and knockout alleles. However, the available mouse models are limited, as most do not allow targeting different ameloblast sub-populations, and constitutive loss of EMPs often results in severe phenotype in the mineral, making it difficult to interpret defect mechanisms. Herein, we report on the design and verification of a toolkit of twelve mouse alleles that include ameloblast-stage specific Cre recombinases, fluorescent reporter alleles, and conditional flox alleles for the major EMPs. We show how these models may be used for applications such as sorting of live stage specific ameloblasts, whole mount imaging, and experiments with incisor explants. The full list of new alleles is available at https://dev.facebase.org/enamelatlas/mouse-models/.

cell biology↗