A5076398843- Cell Image Analysis Techniques
- Medical Image Segmentation Techniques
- AI in cancer detection
- Single-cell and spatial transcriptomics
- Advanced Fluorescence Microscopy Techniques
- Congenital heart defects research
- Hearing, Cochlea, Tinnitus, Genetics
- Advanced Vision and Imaging
- Advanced Electron Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Zebrafish Biomedical Research Applications
- Image Processing Techniques and Applications
- Digital Imaging for Blood Diseases
- Axon Guidance and Neuronal Signaling
- Advanced Neural Network Applications
- Cellular transport and secretion
- Developmental Biology and Gene Regulation
- Hippo pathway signaling and YAP/TAZ
- Radiomics and Machine Learning in Medical Imaging
- Vestibular and auditory disorders
- Cell Adhesion Molecules Research
- MRI in cancer diagnosis
- Neurogenesis and neuroplasticity mechanisms
- Spanish Literature and Culture Studies
- Computer Graphics and Visualization Techniques
Harvard University
2010-2022
Center for Systems Biology
2009-2022
Carnegie Mellon University
2012
The Ohio State University
2006-2008
Continuing the resolution revolution The living cell contains dynamic, spatially complex subassemblies that are sensitive to external perturbations. To minimize such perturbations, cells should be imaged in their native multicellular environments, under as gentle illumination possible. However, achieving spatiotemporal needed follow three-dimensional subcellular processes detail these conditions is challenging: Sample-induced aberrations degrade and sensitivity, high usually requires intense...
Optical and electron microscopy have made tremendous inroads toward understanding the complexity of brain. However, optical offers insufficient resolution to reveal subcellular details, lacks throughput molecular contrast visualize specific constituents over millimeter-scale or larger dimensions. We combined expansion lattice light-sheet image nanoscale spatial relationships between proteins across thickness mouse cortex entire Drosophila These included synaptic at dendritic spines,...
Membrane remodeling is an essential part of transferring components to and from the cell surface membrane-bound organelles for changes in shape, which are particularly critical during division. Earlier analyses, based on classical optical live-cell imaging mostly restricted by technical necessity attached bottom surface, showed persistent formation endocytic clathrin pits vesicles mitosis. Taking advantage resolution, speed, noninvasive illumination newly developed lattice light-sheet...
Epithelial cells acquire functionally important shapes (e.g., squamous, cuboidal, columnar) during development. Here, we combine theory, quantitative imaging, and perturbations to analyze how tissue geometry, cell divisions, mechanics interact shape the presumptive enveloping layer (pre-EVL) on zebrafish embryonic surface. We find that, under geometrical constraints, pre-EVL flattening is regulated by surface number changes following differentially oriented divisions. The division pattern...
The quantification of cell shape, migration, and rearrangements is important for addressing classical questions in developmental biology such as patterning tissue morphogenesis. Time-lapse microscopic imaging transgenic embryos expressing fluorescent reporters the method choice tracking morphogenetic changes establishing lineages fate maps vivo. However, manual steps involved curating thousands putative segmentations have been a major bottleneck application these technologies especially...
Cell segmentation plays a crucial role in understanding, diagnosing, and treating diseases. Despite the recent success of deep learning-based cell methods, it remains challenging to accurately segment densely packed cells 3D membrane images. Existing approaches also require fine-tuning multiple manually selected hyperparameters on new datasets. We develop pipeline, 3DCellSeg, address these challenges. Compared existing our approach carries following novelties: (1) robust two-stage requiring...
Animals make organs of precise size, shape, and symmetry but how developing embryos do this is largely unknown. Here, we combine quantitative imaging, physical theory, physiological measurement hydrostatic pressure fluid transport in zebrafish to study size control the inner ear. We find that accumulation creates lumen leading stress epithelium expansion otic vesicle. Pressure, turn, inhibits into lumen. This negative feedback loop between allows vesicle change growth rate natural or...
The inactivation of the retinoblastoma ( Rb ) tumor suppressor gene in mice results ectopic proliferation, apoptosis, and impaired differentiation extraembryonic, neural, erythroid lineages, culminating fetal death by embryonic day 15.5 (E15.5). Here we show that specific loss trophoblast stem (TS) cells, but not derivatives, leads to an overexpansion trophoblasts, a disruption placental architecture, E15.5. Despite profound abnormalities, tissues appeared remarkably normal, suggesting full...
Rapid advances in microscopy and genetic labeling strategies have created new opportunities for time-lapse imaging of embryonic development. However, methods immobilizing embryos long periods while maintaining normal development changed little. In zebrafish, current immobilization techniques rely on the anesthetic tricaine. Unfortunately, prolonged tricaine treatment at concentrations high enough to immobilize embryo produces undesirable side effects We evaluate three alternative strategies:...
The inner ear is a fluid-filled closed-epithelial structure whose function requires maintenance of an internal hydrostatic pressure and fluid composition. endolymphatic sac (ES) dead-end epithelial tube connected to the unclear. ES defects can cause distended tissue, pathology often seen in hearing balance disorders. Using live imaging zebrafish larvae, we reveal that undergoes cycles slow pressure-driven inflation followed by rapid deflation. Absence these lmx1bb mutants leads tissue....
Developments in optical microscopy imaging have generated large high-resolution data sets that spurred medical researchers to conduct investigations into mechanisms of disease, including cancer at cellular and subcellular levels. The work reported here demonstrates a suitable methodology can be conceived isolates modality-dependent effects from the larger segmentation task 3D reconstructions cognizant shapes as evident available 2D planar images. In current realization, method based on...
Balancing the rate of differentiation and proliferation in developing tissues is essential to produce organs robust size composition. Although many molecular regulators have been established, how these connect physical geometrical aspects tissue architecture poorly understood. Here, using high-resolution timelapse imaging, we find that changes cell geometry associated with dense packing play a significant role regulating zebrafish neural tube. Specifically, progenitors are displaced away...
Inactivation of the retinoblastoma gene in mouse embryos causes tissue infiltrations into critical sections placenta, which has been shown to affect fetal survivability. Our collaborators cancer genetics are extremely interested examining three dimensional nature these given a stack two light microscopy images. Three sets wildtype and mutant placentas was sectioned serially digitized using commercial scanner. Each individual placenta dataset consisted approximately 1000 images totaling 700...
Paired organs in animals are largely bilaterally symmetric despite inherent noise most biological processes. How is precise organ shape and size achieved during development this noise? Examining paired a challenge because it requires repeated quantification of two structures parallel within living embryos. Here we combine bilateral morphology through time with asymmetric perturbations to study regulation shape, size, symmetry developing pairs.
Abstract True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence phenotypes we actually observe, are present. A complete understanding also volumetric cell its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes,...
We propose an anisotropic diffusion method to denoise and aid the reconstruction of planar objects in three-dimensional images. The contribution this paper is development a planarity function characterizing plate-like structures using image Hessian's eigensystem. then construct tensor for anisotropically smoothing plates satisfying necessary scale-space properties. Our finds applications improving fidelity highly noisy cell membrane images from confocal microscopy. In dense cellular regions,...
The authors examine phenotype differences in wildtype and retinoblastoma (Rb) knockout specimens of mouse placenta. Their method for volume visualization tissue-level intermixing at a microscopic scale reveals between the that aren't obvious stack 2D images alone
In analysis of microscopy based images, a major challenge lies in splitting apart cells that appear to overlap because they are too densely packed. This task is complicated by the physics image acquisition causes large variations pixel intensities. Each typically contains thousands with each cell having different orientation, size and intensity histogram. this paper, spatial model nucleus incorporated into [1] aid segmentation from datasets. An energy functional defined it distribution...
Recently, the 2-point correlation functions (2-pcfs) were employed in building feature vectors for histological image segmentation. The 2-pcfs serve as estimators of material distributions with respect to component packing a multi-phase sample. properties estimated by represented tensor structure and HOSVD-based classification algorithm was developed. In this paper, we employ multi-resolution framework scale-space, order achieve significant savings computational costs. We also propose new...
In the last decade, level-set methods have been actively developed for applications in image registration, segmentation, tracking, and reconstruction. However, development of a wide variety PDEs their numerical discretization schemes, coupled with hybrid combinations PDE terms, stopping criteria, reinitialization strategies, has created software logistics problem. absence an integrative design, current toolkits support only specific types implementations which restrict future algorithm since...