ArticleScientific reports2019
Three-dimensional imaging and quantitative analysis in CLARITY processed breast cancer tissues.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Volumetric Cyclic Immunofluorescence for 3D Spatial Profiling of Immune Structures in Human FFPE Tissue.bioRxiv : the preprint server for biology · 2026Article
- ZeroReg3D: a zero-shot registration pipeline for 3D consecutive histopathology image reconstruction.Journal of medical imaging (Bellingham, Wash.) · 2025Article
- A Novel Rat Model to Simulate Positive Margins in the Wound Bed of a Resected Sarcoma.Plastic and reconstructive surgery. Global open · 2024Article
- Rapid full-color serial sectioning tomography with speckle illumination and ultraviolet excitation.Npj imaging · 2024Article
- Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.eLife · 2024Article
- Article
- Structured illumination microscopy for cancer identification in diagnostic breast biopsies.PloS one · 2024Article
- 3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging.Communications biology · 2023Article
- Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time.Frontiers in immunology · 2023Review
- Three-dimensional Imaging Reveals Immune-driven Tumor-associated High Endothelial Venules as a Key Correlate of Tumor Rejection Following Depletion of Regulatory T Cells.Cancer research communications · 2022Article
- Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.Science advances · 2022Article
- Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis.Hepatology communications · 2022Article
- Understanding Breast Cancers through Spatial and High-Resolution Visualization Using Imaging Technologies.Cancers · 2022Review
- 3D imaging for driving cancer discovery.The EMBO journal · 2022Review
- Optical tissue clearing associated with 3D imaging: application in preclinical and clinical studies.Histochemistry and cell biology · 2022Review
- The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies.Cancers · 2022Review
- Monitoring and modulation of the tumor microenvironment for enhanced cancer modeling.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Review
- Spatial analysis of histology in 3D: quantification and visualization of organ and tumor level tissue environment.Heliyon · 2022Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment can be spatially heterogenous, which makes it challenging to fully characterize with standard 2D histology-based methods. In this study, we determined the feasibility of a CLARITY tissue-processing approach to analyze biopsies from breast cancer patients. Formalin-fixed human breast cancer core-needle biopsy specimens, were embedded, lipid-cleared, and multiplexed immunostained to identify key biomarkers (pan-cytokeratin, Ki67, CD3). Confocal microscopy was then used to image the specimens after refractive index matching. These data sets were then quantitatively compared to conventional slide-based FFPE histology. Using CLARITY, the gross and cellular morphology of the tissues were well preserved, and high optical transparency was achieved, with the exception of fibrotic regions. Specific staining of various cellular and nuclear markers was achieved using optimized antibody conditions. Manually determined composite Ki67 scores from the CLARITY datasets agreed with histology results. However, the CLARITY datasets (3D) revealed variation in the intra-tumoral Ki67 expression that was not evident in individual FFPE sections (2D). We further demonstrated that archived FFPE clinical specimens can be CLARITY-processed, immunostained, and imaged. In short, CLARITY-processed specimens may enable a more accurate, unbiased analysis of tumor samples in comparison to conventional slide-based histology, thus allowing for improved visualization of intra-tumoral heterogeneity.
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