Colour deconvolution: stain unmixing in histological imaging

Landini, Gabriel; Martinelli, Giovanni; Piccinini, Filippo

doi:10.1093/bioinformatics/btaa847

Cited by 115 publications

(65 citation statements)

References 4 publications

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“…Such a numerical evaluation allows for the reproducible evaluation of color information of histological and immunohistological stains. [ 64 ] Color deconvolution was performed in ImageJ (National Institutes of Health, USA, v1.52n). Images from three representative regions were analyzed for each sample (Figure S15a,b: Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

Fisch

Broguière

Finkielsztein

et al. 2021

Adv Funct Materials

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Bioprinting of functional tissues could overcome tissue shortages and allow a more rapid response for treatments. However, despite recent progress in bioprinting, and its outstanding ability to position cells and biomaterials in a precise 3D manner, its success has been limited, due to insufficient maturation of constructs into functional tissue. Here, a novel calcium‐triggered enzymatic crosslinking (CTEC) mechanism for bioinks based on the activation cascade of Factor XIII is presented and utilized for the biofabrication of cartilaginous constructs. Hyaluronan transglutaminase (HA‐TG), an enzymatically crosslinkable material, has shown excellent characteristics for chondrogenesis and builds the basis of the CTEC bioink. The bioink supports tissue maturation with neocartilage formation and stiffening of constructs up to 400 kPa. Bioprinted constructs remain stable in vivo for 24 weeks and bioprinted auricular constructs transform into cartilaginous grafts. A major limitation of the current study is the deposition of collagen I, indicating the maturation toward fibrocartilage rather than elastic cartilage. Shifting the maturation process toward elastic cartilage will therefore be essential in order for the developed bioinks to offer a novel tissue engineered treatment for microtia patients. CTEC bioprinting furthermore opens up use of enzymatically crosslinkable biopolymers and their modularity to support a multitude of tissues.

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Section: Methodsmentioning

confidence: 99%

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

Fisch

Broguière

Finkielsztein

et al. 2021

Adv Funct Materials

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“…Collagen deposition was determined on the trichrome-stained kidney sections. The positive area was quantitatively measured using NIH Image J 1.60 software as described previously 38,39 . For Glomerulosclerosis (GS, fibrotic glomeruli) score, it was done as follows: 0, no fibrosis; 1, fibrosis area <25%; 2, fibrosis area = 26-50%; 3, fibrosis area = 51-75%; and 4, fibrosis area >75% as described previously 40,41 .…”

Section: Masson's Trichrome Stainingmentioning

confidence: 99%

Role of tubular epithelial arginase-II in renal inflammaging

et al. 2021

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The aging kidney undergoes complex changes and is vulnerable to injury and development of chronic kidney disease (CKD) with preponderance affecting more women than men. Evidence has been presented that the type-II L-arginine:ureohydrolase, arginase-II (Arg-II) plays a role in the acceleration of aging. Arg-II is highly expressed in the kidney. However, the role of Arg-II in renal aging is not known. This study is to investigate whether Arg-II is involved in the kidney aging process dependently on sex. Arg-II level in the kidney of wild type (WT) mice is significantly elevated with aging, which is accompanied by an increase in expression of the inflammatory cytokines/chemokines, tissue macrophages, factors involved in fibrosis, and tubulointestitial fibrosis in both males and females. This renal aging phenotype is significantly suppressed in arg-II−/− mice, mainly in the females in which Arg-II level is higher than in the males. Importantly, numerous factors such as IL-1β, MCP1, VCAM-1, and TGFβ1 are mainly localized in the proximal tubular S3 segment cells expressing Arg-II in the aging kidney. In human proximal tubular cells (HK-2), TNF-α enhances adhesion molecule expression dependently on Arg-II upregulation. Overexpression of Arg-II in the cells enhances TGFβ1 levels which is prevented by mitochondrial ROS inhibition. In summary, our study reveals that renal proximal tubular Arg-II plays an important role in the kidney aging process in females. Arg-II could be a promising therapeutic target for the treatment and prevention of aging-associated kidney diseases.

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“…The target areas of tumors were identified at a low magnification with an optical microscope (Olympus BX53), and then the images of CAFs and collagen fibers were collected from a randomly selected field of the target areas at a magnification of 40x. The area ratios of α-SMA + CAF (Fig 1 ) and the bluestained area (collagen fibers) (Fig 2 ) on MTS were determined using the image analysis software program "ImageJ" (version 1.52p, National Institutes of Health, Bethesda, MD, USA) with the plugin "color deconvolution" for stain separation [36,37]. A yellow image was separated from the image of α-SMA + CAF using the separation function for hematoxylin & DAB (H DAB) of the plugin, and a blue image was separated from the image of MTS using the separation function for MTS.…”

Section: Methodsmentioning

confidence: 99%

Abundant intratumoral fibrosis prevents lymphocyte infiltration into peritoneal metastases of colorectal cancer

et al. 2021

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Background Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status. However, recent investigations have demonstrated that intratumoral fibrosis is important as a factor affecting the infiltration of TILs. This study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis. Methods Patients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with CD3&CD8 and intratumoral fibrosis by immunohistochemical staining with α-SMA positive cancer-associated fibroblasts and Masson’s trichrome staining against collagen fibers. The "ImageJ" was used to evaluate fibrosis, and the density of TILs in the dense and sparse areas of fibrosis was calculated. The Immunoscore (IS) was obtained based on the density of CD3+/CD8+TILs in the tumor center and invasive margin of the primary tumor. Results The degree of CD3+/CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver and lung metastases. The area ratio of α-SMA positive cancer-associated fibroblasts and collagen fibers in peritoneal metastases was significantly higher than that of liver and lung metastases. Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area. In the high-IS group of primary tumors, the degree of TIL infiltration in distant metastases was significantly higher than that in the low-IS group. Conclusion The infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.

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Colour deconvolution: stain unmixing in histological imaging

Cited by 115 publications

References 4 publications

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

Role of tubular epithelial arginase-II in renal inflammaging

Abundant intratumoral fibrosis prevents lymphocyte infiltration into peritoneal metastases of colorectal cancer

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