Histopathology in 3D: From three-dimensional reconstruction to multi-stain and multi-modal analysis

Magee, Derek R.; Song, Yi; Gilbert, Stephen; Roberts, Nicholas; Wijayathunga, Nagitha; Wilcox, Ruth K.; Bulpitt, Andrew J.; Treanor, Darren

doi:10.4103/2153-3539.151890

Cited by 42 publications

(45 citation statements)

References 15 publications

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“…Some techniques took advantage from public databases, created by organizations like the Allen Brain Atlas (ABA; http://www.brain-map.org), to map a 3D image generated from data extracted with in situ hybridization (Hibbard and Hawkins, 1984; Ford-Holevinski et al, 1991; Hecksher-Sørensen and Sharpe, 2001) and immunofluorescent protocols (Parfitt et al, 2012; Magee et al, 2015) or after noninvasive optical sectioning with MRI or CT (Höhne and Hanson, 1992; Klein et al, 2010), to match the 3D images of gene expression patterns within the public database. These databases, however, are generally limited to a specific set of genes, animals of a specific age (ABA: embryonic stage, P56) and to a limited number of species.…”

Section: Introductionmentioning

confidence: 99%

A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

et al. 2017

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Several techniques, allowing the reconstruction and visualization of functional, anatomical or molecular information from tissue and organ slices, have been developed over the years. Yet none allow direct comparison without reprocessing the same slices. Alternative methods using publicly available reference maps like the Allen Brain Atlas lack flexibility with respect to age and species. We propose a new approach to reconstruct a segmented region of interest from serial slices by projecting the optical density values representing a given molecular signal to a plane of view of choice, and to generalize the results into a reference map, which is built from the individual maps of all animals under study. Furthermore, to allow quantitative comparison between experimental conditions, a non-parametric pseudo t-test has been implemented. This new mapping tool was applied, optimized and validated making use of an in situ hybridization dataset that represents the spatiotemporal expression changes for the neuronal activity reporter gene zif268, in relation to cortical plasticity induced by monocular enucleation, covering the entire mouse visual cortex. The created top view maps of the mouse brain allow precisely delineating and interpreting 11 extrastriate areas surrounding mouse V1. As such, and because of the opportunity to create a planar projection of choice, these molecular maps can in the future easily be compared with functional or physiological imaging maps created with other techniques such as Ca2+, flavoprotein and optical imaging.

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Section: Introductionmentioning

confidence: 99%

A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

et al. 2017

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“…A 3-dimensional histopathologic analysis may also help quantify LN metastasis more accurately. 35 There were limitations in this study, including a small sample size. The mean intensities were calculated from the 2-dimensional videos generated after postprocessing.…”

Section: Discussionmentioning

confidence: 91%

“…As a subject for a future study, it is possible that the retention of targeted microbubbles may be more accurately obtained by a 3‐dimensional evaluation, especially in heterogeneous LNs. A 3‐dimensional histopathologic analysis may also help quantify LN metastasis more accurately . There were limitations in this study, including a small sample size.…”

Section: Discussionmentioning

confidence: 98%

Performance of Molecular Lymphosonography for Detection and Quantification of Metastatic Involvement in Sentinel Lymph Nodes

Nam

Stapp

Liu

et al. 2018

J of Ultrasound Medicine

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Objectives To assess the performance of molecular lymphosonography with dual‐targeted microbubbles in detecting and quantifying the metastatic involvement in sentinel lymph nodes (SLNs) using a swine melanoma model. Methods Targeted microbubbles were labeled with P‐selectin and αVβ3‐integrin antibodies. Control microbubbles were labeled with immunoglobulin G antibodies. First lymphosonography with Sonazoid (GE Healthcare, Oslo, Norway) was used to identify SLNs. Then dual‐targeted and control microbubbles were injected intravenously to detect and quantify metastatic disease in the SLNs. Distant non‐SLNs were imaged as benign controls. All evaluated lymph nodes (LNs) were surgically removed, and metastatic involvement was characterized by a histopathologic analysis. Two radiologists blinded to histopathologic results assessed the baseline B‐mode images of LNs, and the results were compared to the histologic reference standard. The mean intensities of targeted and control microbubbles within the examined LNs were measured and compared to the LN histologic results. Results Thirty‐five SLNs and 34 non‐SLNs from 13 Sinclair swine were included in this study. Twenty‐one SLNs (62%) were malignant, whereas 100% of non‐SLNs were benign. The sensitivity of B‐mode imaging for metastatic LN diagnosis for both readers was relatively high (90% and 71%), but the specificity was very poor (50% and 58%). The sensitivity and specificity of molecular lymphosonography for metastatic LN detection were 91% and 67%, respectively. The mean intensities from dual‐targeted microbubbles correlated well with the degree of metastatic LN involvement (r = 0.6; P < 0.001). Conclusions Molecular lymphosonography can increase the specificity of metastatic LN detection and provide a measure to quantify the degree of metastatic involvement.

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“…Mostly using every 10th serial section (~50 μm between sections) was sufficient to generate a 3D image . For observation of larger objects, 100 μm gap was acceptable (around 100 sections over 1 cm thickness), and thus, the workload could be dramatically reduced.…”

Section: Discussionmentioning

confidence: 99%

Three‐dimensional reconstruction with serial whole‐mount sections of oral tongue squamous cell carcinoma: A preliminary study

Wang

Chen

et al. 2017

J Oral Pathology Medicine

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Objectives: Margin status and invasion pattern are prognostic factors for oral tongue squamous cell carcinoma (OTSCC). Current methods to identify these factors are limited to 2D observation; it is necessary to explore 3D reconstruction with whole-mount sample to improve the accuracy of analysis. This study aimed to study the tissue preparation, section generation, and 3D reconstruction with whole-mount OTSCC specimen.Study design: Two OTSCC samples were retrieved from Nanjing Stomatological Hospital, Medical School of Nanjing University. One sample was sliced into 3 equalsized pieces and subjected to different processing schedules to determine the best method. The second sample was processed accordingly. Serial whole-mount sections of the second sample were generated, stained with HE/anticytokine antibody in intersection manner, and scanned into digital images. Digital images were aligned and reconstructed into 3D images with Hetero Genius Medical Image Manager 3D Pathology Add-On [HGMIM3D].Results: Successful serial whole-mount sections of comparable quality to traditional sections were generated. Three-dimensional images with serial whole-mount sections were successfully generated.Conclusions: Whole-mount histopathological 3D reconstruction of OTSCC was successfully generated, providing a solid foundation for comprehensive margin and invasion analysis. Although future study and improvement were needed, wholemount histopathological 3D reconstruction proved to be a promising method in OTSCC study. K E Y W O R D Sinvasion, margin status, oral tongue squamous cell carcinoma, serial whole-mount sections, three-dimensional reconstruction

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Histopathology in 3D: From three-dimensional reconstruction to multi-stain and multi-modal analysis

Cited by 42 publications

References 15 publications

A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

Performance of Molecular Lymphosonography for Detection and Quantification of Metastatic Involvement in Sentinel Lymph Nodes

Three‐dimensional reconstruction with serial whole‐mount sections of oral tongue squamous cell carcinoma: A preliminary study

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