Three-Dimensional Virtual Microscopy of Colorectal Biopsies

Wu, Mark Li-cheng; Varga, Viktor Sebestyén; Kamaras, Viktor; Ficsor, Levente; Tagscherer, Attila; Tulassay, Zsolt; Molnár, Béla

doi:10.5858/2005-129-507-tvmocb

Cited by 24 publications

(7 citation statements)

References 7 publications

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“…17 Meanwhile, several studies have assessed 3D imaging of colorectal tissue. 18,19 However, the morphological features of CRC spreading at Auerbach's plexus have not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Three‐dimensional imaging of intramural perineural invasion in colorectal cancer: Three‐dimensional reconstruction approach with multiple immunohistochemically stained sections

Miyashita

Ikeda

Shinto

et al. 2022

Pathology International

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Perineural invasion (PNI) at Auerbach's plexus in colorectal cancer (CRC), known as intramural PNI, is associated with adverse prognostic outcomes. This study aimed to characterize the three‐dimensional (3D) architecture of CRC with intramural PNI and to evaluate the morphological features of tumor invasion around nerve tissue. Serial tissue sections from two cases of CRC were stained with cytokeratin AE1/AE3 and an anti‐S‐100 protein antibody. 3D models were reconstructed by scanning the virtual slides. In one case, intramural PNI was observed at the horizontal invasive front. The 3D reconstruction model showed tumor cells that appeared to infiltrate along the nervous meshwork, the structure of which was preserved. In the other case, intramural PNI was observed both at and behind the horizontal invasive front, and the 3D reconstruction model showed that the tumor cells appeared to be involved with nerve cells at the focal part of the horizontal invasive front. However, the nervous meshwork structure was not well identified in cancer‐involved areas. This is the first study to characterize the 3D structure of tumor invasion around nerve tissue in CRC, demonstrating the morphological features of intramural PNI in CRC.

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“…17 Meanwhile, several studies have assessed 3D imaging of colorectal tissue. 18,19 However, the morphological features of CRC spreading at Auerbach's plexus have not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Three‐dimensional imaging of intramural perineural invasion in colorectal cancer: Three‐dimensional reconstruction approach with multiple immunohistochemically stained sections

Miyashita

Ikeda

Shinto

et al. 2022

Pathology International

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“…Onozato et al [91] reconstructed adenocarcinomas of the lung using a former version of the CaseViewer software (3DHistech Ltd., Budapest, Hungary). Another predecessor of CaseViewer was used by Wu et al [92] to reconstruct colorectal biopsies. Tovbis et al [60] additionally segmented the fascicles in the reconstructed tissue.…”

Section: Non-automatic Methodsmentioning

confidence: 99%

Towards Realistic 3D Models of Tumor Vascular Networks

Lindemann,

Glänzer,

Roeth

et al. 2023

Cancers

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For reliable in silico or in vitro investigations in, for example, biosensing and drug delivery applications, accurate models of tumor vascular networks down to the capillary size are essential. Compared to images acquired with conventional medical imaging techniques, digitalized histological tumor slices have a higher resolution, enabling the delineation of capillaries. Volume rendering procedures can then be used to generate a 3D model. However, the preparation of such slices leads to misalignments in relative slice orientation between consecutive slices. Thus, image registration algorithms are necessary to re-align the slices. Here, we present an algorithm for the registration and reconstruction of a vascular network from histologic slices applied to 169 tumor slices. The registration includes two steps. First, consecutive images are incrementally pre-aligned using feature- and area-based transformations. Second, using the previous transformations, parallel registration for all images is enabled. Combining intensity- and color-based thresholds along with heuristic analysis, vascular structures are segmented. A 3D interpolation technique is used for volume rendering. This results in a 3D vascular network with approximately 400–450 vessels with diameters down to 25–30 µm. A delineation of vessel structures with close distance was limited in areas of high structural density. Improvement can be achieved by using images with higher resolution and or machine learning techniques.

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“…For example, the opaque biopsy of colorectal carcinoma demands a thin tissue section, typically less than 5 μm, for the standard histological examination. Although experienced investigators can apply serial sectioning microscopy to generate consecutive tumor images [14,15] or conceive a virtual 3-dimensional (3-D) vascular structure based on the 2-D micrographs, the artifacts and/or the disconnected information caused by microtome slicing create difficulties to reconstruct the tissue network with precision. Due to the technical difficulties, information about the 3-D morphologies of the tissue networks, including those of the blood vessels, lymphatic vessels, and nerves, are generally not available in the literature to help understand their remodeling and the morphological patterns in lesion progression and cancer development.…”

Section: Introductionmentioning

confidence: 99%

Correction: 3-D Visualization and Quantitation of Microvessels in Transparent Human Colorectal Carcinoma

Liu¹,

Pan²,

Hou³

et al. 2013

PLoS ONE

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Microscopic analysis of tumor vasculature plays an important role in understanding the progression and malignancy of colorectal carcinoma. However, due to the geometry of blood vessels and their connections, standard microtomebased histology is limited in providing the spatial information of the vascular network with a 3-dimensional (3-D) continuum. To facilitate 3-D tissue analysis, we prepared transparent human colorectal biopsies by optical clearing for in-depth confocal microscopy with CD34 immunohistochemistry. Full-depth colons were obtained from colectomies performed for colorectal carcinoma. Specimens were prepared away from (control) and at the tumor site. Taking advantage of the transparent specimens, we acquired anatomic information up to 200 μm in depth for qualitative and quantitative analyses of the vasculature. Examples are given to illustrate: (1) the association between the tumor microstructure and vasculature in space, including the perivascular cuffs of tumor outgrowth, and (2) the difference between the 2-D and 3-D quantitation of microvessels. We also demonstrate that the optically cleared mucosa can be retrieved after 3-D microscopy to perform the standard microtome-based histology (H&E staining and immunohistochemistry) for systematic integration of the two tissue imaging methods. Overall, we established a new tumor histological approach to integrate 3-D imaging, illustration, and quantitation of human colonic microvessels in normal and cancerous specimens. This approach has significant promise to work with the standard histology to better characterize the tumor microenvironment in colorectal carcinoma.

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Three-Dimensional Virtual Microscopy of Colorectal Biopsies

Cited by 24 publications

References 7 publications

Three‐dimensional imaging of intramural perineural invasion in colorectal cancer: Three‐dimensional reconstruction approach with multiple immunohistochemically stained sections

Three‐dimensional imaging of intramural perineural invasion in colorectal cancer: Three‐dimensional reconstruction approach with multiple immunohistochemically stained sections

Towards Realistic 3D Models of Tumor Vascular Networks

Correction: 3-D Visualization and Quantitation of Microvessels in Transparent Human Colorectal Carcinoma

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