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Gee, J. C.

Publications and source records attributed to Gee, J. C..

7 recordsLinked to original sources

Deep Computational Anatomy via Latent-Aligned Multiview Normalizing Flows

In modeling complex probability distributions, normalizing flows provide exact-likelihood, bijective mappings between empirical data and tractable latent spaces. Building on this foundation, latent-aligned multiview normalizing (LAMNr) flows leverage these salient properties to learn shared latent subspaces across heterogeneous, multimodal datasets while simultaneously topologically unfolding the sampled data manifold into a continuous vector space. Formal latent-alignment constraints are used to model shared structural features separate from view-specific variations, coordinating latent projections into a shared geometric subspace. By applying this transformation in the context of biological imaging, the framework establishes a potential basis for a deep learning interpretation of foundational computational anatomy concepts, such as the population template, latent distances, and geodesic pairwise image interpolation. Additionally, the proposed framework enables closed-form conditional modeling for exact cross-view imputation and other latent space manipulations. Evaluations and illustrations on both imaging-derived phenotypes (IDPs) and multimodal MRI demonstrate the proposed framework and potential applications. To further motivate our work, we provide a robust and comprehensive, 2D and 3D open-source implementation in PyTorch, natively integrated with the ANTsX ecosystem (i.e., ANTsTorch) for efficient training and subsequent data transformation, manipulation, and analysis.

bioinformatics↗

Effect of Stroma-directed Drugs in Combination with Chemotherapy Against Pancreatic Cancer- a Preclinical Study

Cytotoxic chemotherapy plays an important role for extending the survival of patients with pancreatic ductal adenocarcinoma (PDAC). To enhance the efficacy of chemotherapy for eradicating the cancer cells, we have compared the standard care chemotherapy (combination of nab-paclitaxel, gemcitabine and cisplatin, NGC) versus NGC plus stroma-directed agents (calcipotriol and losartan, respectively) in a genetically engineered mouse model of PDAC. Over a 2-week study period, MRI was conducted to measure the tumor size and to test the sensitivity of imaging markers derived from diffusion-weighted imaging (DWI), dynamic contrast enhanced MRI (DCE) and magnetization transfer ratio (MTR) for assessing the tumor cellularity and stromal changes. Detailed immunohistochemistry and preliminary single cell RNA sequencing (scRNAseq) study were applied to tumor tissues collected upon euthanasia on day-14. Our major findings are: 1. Compared the untreated controls, NGC chemotherapy induced significant tumor growth inhibition and stromal changes including pronounced reduction of fibroblast associated protein (FAP) level accompanied by increased matrix collagen content, significantly reduced microvascular permeability revealed by DCE corroborated with reduced microvascular density. 2. Losartan+NGC significantly enhanced inhibition of tumor growth beyond NGC and increased lymphocytes infiltration in the tumor which may contribute to enhanced cancer cells eradication. 3. NGC treatment enriched the fraction of mesenchymal (M) subtype while reducing the epithelial (E) subtype of cancer cells compared to the controls, and this trend was reversed by calcipotriol+NGC. In conclusion, our study captured changes in cancer cell and tumor microenvironment in response to chemo stromal therapy versus chemotherapy alone with mechanistic insights.

cancer biology↗

The ANTsX Ecosystem for Mapping the Mouse Brain

Precision mapping techniques coupled with high resolution image acquisition of the mouse brain permit the study of the spatial organization of gene expression and their mutual interaction for a comprehensive view of salient structural/functional relationships. Such research is facilitated by standardized anatomical coordinate systems, such as the well-known Allen Common Coordinate Framework (AllenCCFv3), and the ability to spatially map to such standardized spaces. The Advanced Normalization Tools Ecosystem is a comprehensive open-source software toolkit for generalized quantitative imaging with applicability to multiple organ systems, modalities, and animal species. Herein, we illustrate the utility of ANTsX for generating precision spatial mappings of the mouse brain and potential subsequent quantitation. We describe ANTsX-based workflows for mapping domain-specific image data to AllenCCFv3 accounting for common artefacts and other confounds. Novel contributions include ANTsX functionality for velocity flow-based mapping spanning the spatiotemporal domain of a longitudinal trajectory which we apply to the Developmental Common Coordinate Framework. Additionally, we present an automated structural morphological pipeline for determining volumetric and cortical thickness measurements analogous to the well-utilized ANTsX pipeline for human neuroanatomical structural morphology which illustrates a general open-source framework for tailored brain parcellations.

neuroscience↗

Developmental Mouse Brain Common Coordinate Framework

3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.

neuroscience↗

HiDiver: A Suite of Methods to Merge Magnetic Resonance Histology, Light Sheet Microscopy, and Complete Brain Delineations

We have developed new imaging and computational workflows to produce accurately aligned multimodal 3D images of the mouse brain that exploit high resolution magnetic resonance histology (MRH) and light sheet microscopy (LSM) with fully rendered 3D reference delineations of brain structures. The suite of methods starts with the acquisition of geometrically accurate (in-skull) brain MRIs using multi-gradient echo (MGRE) and new diffusion tensor imaging (DTI) at an isotropic spatial resolution of 15 m. Whole brain connectomes are generated using over 100 diffusion weighted images acquired with gradients at uniformly spaced angles. Track density images are generated at a super-resolution of 5 m. Brains are dissected from the cranium, cleared with SHIELD, stained by immunohistochemistry, and imaged by LSM at 1.8 m/pixel. LSM channels are registered into the reference MRH space along with the Allen Brain Atlas (ABA) Common Coordinate Framework version 3 (CCFv3). The result is a high-dimensional integrated volume with registration (HiDiver) that has a global alignment accuracy of 10-50 m. HiDiver enables 3D quantitative and global analyses of cells, circuits, connectomes, and CNS regions of interest (ROIs). Throughput is sufficiently high that HiDiver is now being used in comprehensive quantitative studies of the impact of gene variants and aging on rodent brain cytoarchitecture.

neuroscience↗

The influence of axial length upon the retinal ganglion cell layer of the human eye

PurposeWe examined the relationship between axial length and the thickness and volume of the ganglion cell layer (GCL) of the retina, and related these measures to the size of the optic chiasm. MethodsWe used optical coherence tomography to measure the thickness of the GCL over a 50{degrees} extent of the horizontal meridian in 50 normally-sighted participants with a wide range of axial lengths. Using a model eye informed by individual biometry, we converted GCL thickness to tissue volume per square degree. The volume of the optic chiasm was measured for 40 participants using magnetic resonance imaging. ResultsWhile GCL thickness decreases with increasing axial length, there is a positive relationship between GCL tissue volume and axial length, leading us to conclude that increasing axial length is associated with decreased retinal ganglion cell packing, increased cell size, or both. We characterize how retinal ganglion cell tissue varies systematically in volume and spatial distribution as a function of axial length. This model allows us to remove the effect of axial length from individual difference measures of GCL volume. We find that variation in GCL volume correlates well with the size of the optic chiasm as measured using magnetic resonance imaging. ConclusionsOur results provide the volume of ganglion cell tissue in the retina, adjusted for the effects of axial length upon ganglion cell size and/or packing. The resulting volume measure accounts for individual differences in the size of the optic chiasm, supporting its use to characterize the post-retinal visual pathway.

neuroscience↗

Interpretable Multimodality Embedding of Cerebral Cortex Using Attention Graph Network for Identifying Bipolar Disorder

Bipolar Disorder (BP) is a mental disorder that affects 1 [~] 2% of the population. Early diagnosis and targeted treatment can benefit from associated biological markers. The existing methods typically utilize biomarkers from anatomical MRI or functional BOLD imaging, but lack the ability of revealing the relationship between integrated modalities and disease. In this paper, we developed an Edge-weighted Graph Attention Network (EGAT) with Dense Hierarchical Pooling (DHP), to better understand the underlying roots of the disorder from the view of structure-function integration. For the input, the underlying graphs are constructed from functional connectivity matrices and the nodal features consist of both the anatomical features and the statistics of the connectivity. We investigated the potential benefits of using EGAT to classify BP vs. Healthy Control (HC). Compared with traditional machine learning classifiers, our proposed EGAT embedding increased improved 10 [~] 20% in the accuracy and F1-score, compared with alternative classifiers. More specifically, by examining the attention map and gradient sensitivity of nodal features, we indicated that associated with the abnormality of anatomical geometric properties, multiple interactive patterns among Default Mode, Fronto-parietal and Cingulo-opercular networks contribute to identifying BP.

neuroscience↗