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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-10-15)
    Abstract: Spatially-resolved molecular profiling by immunostaining tissue sections is a key feature in cancer diagnosis, subtyping, and treatment, where it complements routine histopathological evaluation by clarifying tumor phenotypes. In this work, we present a deep learning-based method called speedy histological-to-immunofluorescent translation (SHIFT) which takes histologic images of hematoxylin and eosin (H & E)-stained tissue as input, then in near-real time returns inferred virtual immunofluorescence (IF) images that estimate the underlying distribution of the tumor cell marker pan-cytokeratin (panCK). To build a dataset suitable for learning this task, we developed a serial staining protocol which allows IF and H & E images from the same tissue to be spatially registered. We show that deep learning-extracted morphological feature representations of histological images can guide representative sample selection, which improved SHIFT generalizability in a small but heterogenous set of human pancreatic cancer samples. With validation in larger cohorts, SHIFT could serve as an efficient preliminary, auxiliary, or substitute for panCK IF by delivering virtual panCK IF images for a fraction of the cost and in a fraction of the time required by traditional IF.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-12-01)
    Abstract: Mechanistic disease progression studies using animal models require objective and quantifiable assessment of tissue pathology. Currently quantification relies heavily on staining methods which can be expensive, labor/time-intensive, inconsistent across laboratories and batch, and produce uneven staining that is prone to misinterpretation and investigator bias. We developed an automated semantic segmentation tool utilizing deep learning for rapid and objective quantification of histologic features relying solely on hematoxylin and eosin stained pancreatic tissue sections. The tool segments normal acinar structures, the ductal phenotype of acinar-to-ductal metaplasia (ADM), and dysplasia with Dice coefficients of 0.79, 0.70, and 0.79, respectively. To deal with inaccurate pixelwise manual annotations, prediction accuracy was also evaluated against biological truth using immunostaining mean structural similarity indexes (SSIM) of 0.925 and 0.920 for amylase and pan-keratin respectively. Our tool’s disease area quantifications were correlated to the quantifications of immunostaining markers (DAPI, amylase, and cytokeratins; Spearman correlation score = 0.86, 0.97, and 0.92) in unseen dataset (n = 25). Moreover, our tool distinguishes ADM from dysplasia, which are not reliably distinguished with immunostaining, and demonstrates generalizability across murine cohorts with pancreatic disease. We quantified the changes in histologic feature abundance for murine cohorts with oncogenic Kras-driven disease, and the predictions fit biological expectations, showing stromal expansion, a reduction of normal acinar tissue, and an increase in both ADM and dysplasia as disease progresses. Our tool promises to accelerate and improve the quantification of pancreatic disease in animal studies and become a unifying quantification tool across laboratories.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-014-PO-014
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-014-PO-014
    Abstract: Objective and quantifiable assessment of tissue pathology is necessary to study mechanistic disease progression; however, current quantification methods based on tissue staining have many drawbacks including cost, time, labor, batch effects, as well as uneven staining which can result in misinterpretation and investigator bias. Here we present VISTA, an automated deep learning tool for semantic segmentation and quantification of histologic features from hematoxylin and eosin (H & E) stained pancreatic tissue sections. VISTA is trained to identify four key tissue types in developing murine PDAC samples: normal acinar, acinar-to-ductal metaplasia (ADM), dysplasia, and other normal tissue. Predicted segmentations were quantitatively evaluated against pathologist annotation with Dice Coefficients, achieving scores of 0.79, 0.70, 0.79 for normal acinar, ADM, and dysplasia, respectively. Predictions were evaluated against biological ground truth using the mean structural similarity index to immunostainings amylase and pan-keratin (0.925 and 0.920, respectively). The total area of feature prediction was also correlated to the area of immunostaining in whole tissue sections using spearman correlation (0.86, 0.97, and 0.92 for DAPI, amylase, and cytokeratins, respectively). Importantly, our tool is not only able to predict staining information, but it is able to distinguish between ADM and dysplasia, which are not reliably distinguished with common immunostaining methods, showing VISTA’s potential to expand research beyond what is capable with current standards. As a use case example of VISTA, we quantified abundance of histologic features in murine cohorts with oncogenic Kras-driven disease. We observed stromal expansion, a reduction in normal acinar, and an increase in both ADM and dysplasia as the disease progresses, which matches known biology. Since VISTA is an automated algorithm, it can accelerate histological analysis and improve the consistency of quantification between laboratories and investigators. This work has been published in Nature Scientific Reports, and the code is available on github at https://github.com/GelatinFrogs/MicePan-Segmentation. Citation Format: Luke Ternes, Ge Huang, Christian Lanciault, Guillaume Thibault, Rachelle Riggers, Joe Gray, John Muschler, Young Hwan Chang. VISTA: VIsual Semantic Tissue Analysis for pancreatic disease quantification in murine cohorts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-014.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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