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  1. Article ; Online: Visual Prompting Based Incremental Learning for Semantic Segmentation of Multiplex Immuno-Flourescence Microscopy Imagery.

    Faulkenberry, Ryan / Prasad, Saurabh / Maric, Dragan / Roysam, Badrinath

    Neuroinformatics

    2024  Volume 22, Issue 2, Page(s) 147–162

    Abstract: Deep learning approaches are state-of-the-art for semantic segmentation of medical images, but unlike many deep learning applications, medical segmentation is characterized by small amounts of annotated training data. Thus, while mainstream deep learning ...

    Abstract Deep learning approaches are state-of-the-art for semantic segmentation of medical images, but unlike many deep learning applications, medical segmentation is characterized by small amounts of annotated training data. Thus, while mainstream deep learning approaches focus on performance in domains with large training sets, researchers in the medical imaging field must apply new methods in creative ways to meet the more constrained requirements of medical datasets. We propose a framework for incrementally fine-tuning a multi-class segmentation of a high-resolution multiplex (multi-channel) immuno-flourescence image of a rat brain section, using a minimal amount of labelling from a human expert. Our framework begins with a modified Swin-UNet architecture that treats each biomarker in the multiplex image separately and learns an initial "global" segmentation (pre-training). This is followed by incremental learning and refinement of each class using a very limited amount of additional labeled data provided by a human expert for each region and its surroundings. This incremental learning utilizes the multi-class weights as an initialization and uses the additional labels to steer the network and optimize it for each region in the image. In this way, an expert can identify errors in the multi-class segmentation and rapidly correct them by supplying the model with additional annotations hand-picked from the region. In addition to increasing the speed of annotation and reducing the amount of labelling, we show that our proposed method outperforms a traditional multi-class segmentation by a large margin.
    MeSH term(s) Humans ; Animals ; Rats ; Microscopy ; Semantics
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2111941-7
    ISSN 1559-0089 ; 1539-2791
    ISSN (online) 1559-0089
    ISSN 1539-2791
    DOI 10.1007/s12021-024-09651-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Visual Prompting based Incremental Learning for Semantic Segmentation of Multiplex Immuno-Flourescence Microscopy Imagery.

    Faulkenberry, Ryan / Prasad, Saurabh / Maric, Dragan / Roysam, Badrinath

    Research square

    2023  

    Abstract: Deep learning approaches are state-of-the-art for semantic segmentation of medical images, but unlike many deep learning applications, medical segmentation is characterized by small amounts of annotated training data. Thus, while mainstream deep learning ...

    Abstract Deep learning approaches are state-of-the-art for semantic segmentation of medical images, but unlike many deep learning applications, medical segmentation is characterized by small amounts of annotated training data. Thus, while mainstream deep learning approaches focus on performance in domains with large training sets, researchers in the medical imaging field must apply new methods in creative ways to meet the more constrained requirements of medical datasets. We propose a framework for incrementally fine-tuning a multi-class segmentation of a high-resolution multiplex (multi-channel) immuno-flourescence image of a rat brain section, using a minimal amount of labelling from a human expert. Our framework begins with a modified Swin-UNet architecture that treats each biomarker in the multiplex image separately and learns an initial "global" segmentation (
    Language English
    Publishing date 2023-12-25
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3783494/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Comparative overview of multi-shell diffusion MRI models to characterize the microstructure of multiple sclerosis lesions and periplaques.

    Vanden Bulcke, Colin / Stölting, Anna / Maric, Dragan / Macq, Benoît / Absinta, Martina / Maggi, Pietro

    NeuroImage. Clinical

    2024  Volume 42, Page(s) 103593

    Abstract: In multiple sclerosis (MS), accurate in vivo characterization of the heterogeneous lesional and extra-lesional tissue pathology remains challenging. Marshalling several advanced imaging techniques - quantitative relaxation time (T1) mapping, a model-free ...

    Abstract In multiple sclerosis (MS), accurate in vivo characterization of the heterogeneous lesional and extra-lesional tissue pathology remains challenging. Marshalling several advanced imaging techniques - quantitative relaxation time (T1) mapping, a model-free average diffusion signal approach and four multi-shell diffusion models - this study investigates the performance of multi-shell diffusion models and characterizes the microstructural damage within (i) different MS lesion types - active, chronic active, and chronic inactive - (ii) their respective periplaque white matter (WM), and (iii) the surrounding normal-appearing white matter (NAWM). In 83 MS participants (56 relapsing-remitting, 27 progressive) and 23 age and sex-matched healthy controls (HC), we analysed a total of 317 paramagnetic rim lesions (PRL+), 232 non-paramagnetic rim lesions (PRL-), 38 contrast-enhancing lesions (CEL). Consistent with previous findings and histology, our analysis revealed the ability of advanced multi-shell diffusion models to characterize the unique microstructural patterns of CEL, and to elucidate their possible evolution into a resolving (chronic inactive) vs smoldering (chronic active) inflammatory stage. In addition, we showed that the microstructural damage extends well beyond the MRI-visible lesion edge, gradually fading out while moving outward from the lesion edge into the immediate WM periplaque and the NAWM, the latter still characterized by diffuse microstructural damage in MS vs HC. This study also emphasizes the critical role of selecting appropriate diffusion models to elucidate the complex pathological architecture of MS lesions and their periplaque. More specifically, multi-compartment diffusion models based on biophysically interpretable metrics such as neurite orientation dispersion and density (NODDI; mean auc=0.8002) emerge as the preferred choice for MS applications, while simpler models based on a representation of the diffusion signal, like diffusion tensor imaging (DTI; mean auc=0.6942), consistently underperformed, also when compared to T1 mapping (mean auc=0.73375).
    Language English
    Publishing date 2024-03-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2701571-3
    ISSN 2213-1582 ; 2213-1582
    ISSN (online) 2213-1582
    ISSN 2213-1582
    DOI 10.1016/j.nicl.2024.103593
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Metabolic Quadrivalency in RSeT Human Embryonic Stem Cells.

    Chen, Kevin G / Park, Kyeyoon / Maric, Dragan / Johnson, Kory R / Robey, Pamela G / Mallon, Barbara S

    bioRxiv : the preprint server for biology

    2024  

    Abstract: One of the most important properties of human embryonic stem cells (hESCs) is related to their pluripotent states. In our recent study, we identified a previously unrecognized pluripotent state induced by RSeT medium. This state makes primed hESCs ... ...

    Abstract One of the most important properties of human embryonic stem cells (hESCs) is related to their pluripotent states. In our recent study, we identified a previously unrecognized pluripotent state induced by RSeT medium. This state makes primed hESCs resistant to conversion to naïve pluripotent state. In this study, we have further characterized the metabolic features in these RSeT hESCs, including metabolic gene expression, metabolomic analysis, and various functional assays. The commonly reported metabolic modes include glycolysis or both glycolysis and oxidative phosphorylation (i.e., metabolic bivalency) in pluripotent stem cells. However, besides the presence of metabolic bivalency, RSeT hESCs exhibited a unique metabolome with additional fatty acid oxidation and imbalanced nucleotide metabolism. This metabolic quadrivalency is linked to hESC growth independent of oxygen tension and restricted capacity for naïve reprogramming in these cells. Thus, this study provides new insights into pluripotent state transitions and metabolic stress-associated hPSC growth
    Language English
    Publishing date 2024-02-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.21.581486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cellular data extraction from multiplexed brain imaging data using self-supervised Dual-loss Adaptive Masked Autoencoder.

    Ly, Son T / Lin, Bai / Vo, Hung Q / Maric, Dragan / Roysam, Badrinath / Nguyen, Hien V

    Artificial intelligence in medicine

    2024  Volume 151, Page(s) 102828

    Abstract: Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology ... ...

    Abstract Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations. In addition, to examine the generalizability of DAMA, we also experimented on TissueNet, a multiplexed imaging dataset comprised of two-channel fluorescence images from six distinct tissue types, captured using six different imaging platforms. Our code is publicly available at https://github.com/hula-ai/DAMA.
    MeSH term(s) Brain/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; Supervised Machine Learning ; Humans ; Deep Learning ; Animals ; Algorithms ; Neuroimaging/methods
    Language English
    Publishing date 2024-03-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 645179-2
    ISSN 1873-2860 ; 0933-3657
    ISSN (online) 1873-2860
    ISSN 0933-3657
    DOI 10.1016/j.artmed.2024.102828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells.

    Jiao, Song / Miranda, Pablo / Li, Yan / Maric, Dragan / Holmgren, Miguel

    Heliyon

    2023  Volume 9, Issue 8, Page(s) e18754

    Abstract: The accessory protein ORF3a, from SARS-CoV-2, plays a critical role in viral infection and pathogenesis. Here, we characterized ORF3a assembly, ion channel activity, subcellular localization, and interactome. At the plasma membrane, ORF3a exists mostly ... ...

    Abstract The accessory protein ORF3a, from SARS-CoV-2, plays a critical role in viral infection and pathogenesis. Here, we characterized ORF3a assembly, ion channel activity, subcellular localization, and interactome. At the plasma membrane, ORF3a exists mostly as monomers and dimers, which do not alter the native cell membrane conductance, suggesting that ORF3a does not function as a viroporin at the cell surface. As a membrane protein, ORF3a is synthesized at the ER and sorted via a canonical route. ORF3a overexpression induced an approximately 25% increase in cell death. By developing an APEX2-based proximity labeling assay, we uncovered proteins proximal to ORF3a, suggesting that ORF3a recruits some host proteins to weaken the cell. In addition, it exposed a set of mitochondria related proteins that triggered mitochondrial fission. Overall, this work can be an important instrument in understanding the role of ORF3a in the virus pathogenicity and searching for potential therapeutic treatments for COVID-19.
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e18754
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  7. Article ; Online: scRNA-seq data from the larval Drosophila ventral cord provides a resource for studying motor systems function and development.

    Nguyen, Tho Huu / Vicidomini, Rosario / Choudhury, Saumitra Dey / Han, Tae Hee / Maric, Dragan / Brody, Thomas / Serpe, Mihaela

    Developmental cell

    2024  

    Abstract: The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated ... ...

    Abstract The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes. We discovered a glutamate receptor subunit required for basal neurotransmission and homeostasis at the larval neuromuscular junction. We describe larval glia and endorse the general view that glia perform consistent activities throughout development. This census represents an extensive resource and a powerful platform for future discoveries of cellular and molecular mechanisms in repair, regeneration, plasticity, homeostasis, and behavioral coordination.
    Language English
    Publishing date 2024-03-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2024.03.016
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  8. Article ; Online: Flow cytometric immunophenotypic differentiation patterns of bone marrow eosinophilopoiesis.

    Trindade, Christopher J / Sun, Xiaoping / Maric, Dragan / Sharma, Sachein / Komarow, Hirsh D / Hourigan, Christopher S / Klion, Amy / Maric, Irina

    Cytometry. Part B, Clinical cytometry

    2024  

    Abstract: Background: Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. ... ...

    Abstract Background: Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. Eosinophils play an important role in a wide variety of disorders, including some myeloid neoplasms. However, changes in flow cytometric immunophenotypic patterns during normal and abnormal bone marrow eosinophilopoiesis have not been well studied.
    Methods: Fresh bone marrow aspirates from 15 healthy donors, 19 patients with hypereosinophilic syndromes (HES), and 11 patients with systemic mastocytosis (SM) were analyzed for candidate markers that included EMR-1, Siglec-8, CCR3, CD9, CD11a, CD11b, CD11c, CD13, CD16, CD29, CD34, CD38, CD45, CD44, CD49d, CD49f, CD54, CD62L, CD69, CD117, CD125 (IL-5Rα), HLA-DR, using 10 parameter flow cytometry. Putative CD34-negative immature and mature normal eosinophil populations were first identified based on changes in expression of the above markers in healthy donors, then confirmed using fluorescence-based cell sorting and morphological evaluation of cytospin preparations. The normal immunophenotypic patterns were then compared to immunophenotypic patterns of eosinophilopoiesis in patients with HES and SM.
    Results: The eosinophilic lineage was first verified using the human eosinophil-specific antibody EMR-1 in combination with anti-IL-5Rα antibody. Then, a combination of Siglec-8, CD9, CD11b, CCR3, CD49d, and CD49f antibodies was used to delineate normal eosinophilic maturational patterns. Early stages (eosinophilic promyelocytes/myelocytes) were identified as Siglec-8 dim/CD11b dim to moderate/CD9 dim/CCR3 dim/CD49d bright/CD49f dim, intermediate stages (eosinophilic myelocytes/metamyelocytes) as Siglec-8 moderate/CD11b moderate to bright/CD9 moderate/CCR3 moderate/CD49d moderate/CD49f moderate and mature bands/segmented eosinophils as Siglec-8 bright/CD11b bright/CD9 bright/CCR3 bright/CD49d dim/CD49f bright. Overall maturational patterns were also similar in patients with HES and SM; however, the expression levels of several surface markers were altered compared to normal eosinophils.
    Conclusion: A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2099657-3
    ISSN 1552-4957 ; 1552-4949 ; 0196-4763
    ISSN (online) 1552-4957
    ISSN 1552-4949 ; 0196-4763
    DOI 10.1002/cyto.b.22174
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Monocyte-derived IL-6 programs microglia to rebuild damaged brain vasculature.

    Choi, Bo-Ran / Johnson, Kory R / Maric, Dragan / McGavern, Dorian B

    Nature immunology

    2023  Volume 24, Issue 7, Page(s) 1110–1123

    Abstract: Cerebrovascular injury (CVI) is a common pathology caused by infections, injury, stroke, neurodegeneration and autoimmune disease. Rapid resolution of a CVI requires a coordinated innate immune response. In the present study, we sought mechanistic ... ...

    Abstract Cerebrovascular injury (CVI) is a common pathology caused by infections, injury, stroke, neurodegeneration and autoimmune disease. Rapid resolution of a CVI requires a coordinated innate immune response. In the present study, we sought mechanistic insights into how central nervous system-infiltrating monocytes program resident microglia to mediate angiogenesis and cerebrovascular repair after an intracerebral hemorrhage. In the penumbrae of human stroke brain lesions, we identified a subpopulation of microglia that express vascular endothelial growth factor A. These cells, termed 'repair-associated microglia' (RAMs), were also observed in a rodent model of CVI and coexpressed interleukin (IL)-6Ra. Cerebrovascular repair did not occur in IL-6 knockouts or in mice lacking microglial IL-6Ra expression and single-cell transcriptomic analyses revealed faulty RAM programming in the absence of IL-6 signaling. Infiltrating CCR2
    MeSH term(s) Mice ; Humans ; Animals ; Monocytes ; Microglia ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Stroke/pathology ; Brain/metabolism ; Mice, Inbred C57BL
    Chemical Substances Interleukin-6 ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2023-05-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01521-1
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  10. Article ; Online: Cell specificity of Manganese-enhanced MRI signal in the cerebellum.

    Rallapalli, Harikrishna / Bayin, N Sumru / Goldman, Hannah / Maric, Dragan / Nieman, Brian J / Koretsky, Alan P / Joyner, Alexandra L / Turnbull, Daniel H

    NeuroImage

    2023  Volume 276, Page(s) 120198

    Abstract: Magnetic Resonance Imaging (MRI) resolution continues to improve, making it important to understand the cellular basis for different MRI contrast mechanisms. Manganese-enhanced MRI (MEMRI) produces layer-specific contrast throughout the brain enabling in ...

    Abstract Magnetic Resonance Imaging (MRI) resolution continues to improve, making it important to understand the cellular basis for different MRI contrast mechanisms. Manganese-enhanced MRI (MEMRI) produces layer-specific contrast throughout the brain enabling in vivo visualization of cellular cytoarchitecture, particularly in the cerebellum. Due to the unique geometry of the cerebellum, especially near the midline, 2D MEMRI images can be acquired from a relatively thick slice by averaging through areas of uniform morphology and cytoarchitecture to produce very high-resolution visualization of sagittal planes. In such images, MEMRI hyperintensity is uniform in thickness throughout the anterior-posterior axis of sagittal sections and is centrally located in the cerebellar cortex. These signal features suggested that the Purkinje cell layer, which houses the cell bodies of the Purkinje cells and the Bergmann glia, is the source of hyperintensity. Despite this circumstantial evidence, the cellular source of MRI contrast has been difficult to define. In this study, we quantified the effects of selective ablation of Purkinje cells or Bergmann glia on cerebellar MEMRI signal to determine whether signal could be assigned to one cell type. We found that the Purkinje cells, not the Bergmann glia, are the primary of source of the enhancement in the Purkinje cell layer. This cell-ablation strategy should be useful for determining the cell specificity of other MRI contrast mechanisms.
    MeSH term(s) Humans ; Manganese/metabolism ; Cerebellum/pathology ; Purkinje Cells/metabolism ; Purkinje Cells/pathology ; Neuroglia/metabolism ; Magnetic Resonance Imaging/methods
    Chemical Substances Manganese (42Z2K6ZL8P)
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2023.120198
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