3D imaging for driving cancer discovery

Ineveld, Ravian L. van; Vliet, Esmée J. van; Wehrens, Ellen J.; Alieva, María; Rios, Anne C.

doi:10.15252/embj.2021109675

Cited by 9 publications

(4 citation statements)

References 227 publications

(316 reference statements)

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“…While three dimensional radiologic imaging is frequently used to study the biomechanical behavior of aortic aneurysms, 3D histology has been mostly reported to improve diagnostic accuracy and visualization in cancer specimen [ 37 ]. Both, HE and immunofluorescence for vessel imaging have been applied, [ 15 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Completing the view – histologic insights from circular AAA specimen including 3D imaging

Menges,

Nackenhorst,

Müller

et al. 2023

Diagn Pathol

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Abdominal aortic aneurysm (AAA) is a pathologic enlargement of the infrarenal aorta with an associated risk of rupture. However, the responsible mechanisms are only partially understood. Based on murine and human samples, a heterogeneous distribution of characteristic pathologic features across the aneurysm circumference is expected. Yet, complete histologic workup of the aneurysm sac is scarcely reported. Here, samples from five AAAs covering the complete circumference partially as aortic rings are investigated by histologic means (HE, EvG, immunohistochemistry) and a new method embedding the complete ring. Additionally, two different methods of serial histologic section alignment are applied to create a 3D view. The typical histopathologic features of AAA, elastic fiber degradation, matrix remodeling with collagen deposition, calcification, inflammatory cell infiltration and thrombus coverage were distributed without recognizable pattern across the aneurysm sac in all five patients. Analysis of digitally scanned entire aortic rings facilitates the visualization of these observations. Immunohistochemistry is feasible in such specimen, however, tricky due to tissue disintegration. 3D image stacks were created using open-source and non-generic software correcting for non-rigid warping between consecutive sections. Secondly, 3D image viewers allowed visualization of in-depth changes of the investigated pathologic hallmarks. In conclusion, this exploratory descriptive study demonstrates a heterogeneous histomorphology around the AAA circumference. Warranting an increased sample size, these results might need to be considered in future mechanistic research, especially in reference to intraluminal thrombus coverage. 3D histology of such circular specimen could be a valuable visualization tool for further analysis.

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Section: Discussionmentioning

confidence: 99%

Completing the view – histologic insights from circular AAA specimen including 3D imaging

Menges,

Nackenhorst,

Müller

et al. 2023

Diagn Pathol

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“…Recent research on tissue clearing methods has made it possible to make the bodies and organs of laboratory animals transparent [ 16 , 17 ]. Furthermore, the advent of volumetric immunohistochemistry on transparent tissue has made it possible to elucidate the 3D pathology of human tumors, thereby revealing the 3D structure of the tumor microenvironment at the single‐cell level [ 3 , 18 , 19 ]. Although organic solvent methods such as the DIPCO protocol used in this study are not suitable for the retention of endogenous fluorescent proteins [ 8 , 20 ], this clearing protocol not only provides excellent transparency but is also quick and easy to perform and can be combined with antibody staining for detailed observation [ 1 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tumors are heterogeneous and complex in three dimensions (3Ds), and it is difficult to obtain a complete picture of a tumor with a two‐dimensional view [ 1 , 2 ]. To date, the importance of the 3D structure and spatial distribution of the vasculature has not been discussed because of the inability to visualize the inherently heterogeneous tumor space formed by complex cell populations and a mixture of 3D vascular and layered structures in solid cancers [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma

Kaneko,

Masuda,

Takamatsu

et al. 2024

The Journal of Pathology CR

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Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two‐dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three‐dimensional light‐sheet microscopy. Here, we used the diagnosing immunolabeled paraffin‐embedded cleared organs pipeline for tissue clearing, immunolabeling, and three‐dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE‐1, which targets lymphatic vessels, were examined by calculating three‐dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin‐fixed paraffin‐embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three‐dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K‐mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High‐end tissue clearing techniques and volumetric immunohistochemistry enable three‐dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.

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“…Only recently (Huang et al., 2021; Vogt, 2020) has embryo development within the uterus been imaged with two‐photon microscopy rather than ultrasound or MRI. In oncology, intravital microscopy on mouse models is increasingly being applied to record the complex behavior of cancerous and immune cells during the progress and metastasis of tumors (Dzhagalov et al, 2012; Perrin, Bayarmagnai, & Gligorijevic, 2020; van Ineveld, van Vliet, Wehrens, Alieva, & Rios, 2022; van Rheenen & Scheele, 2021), which static observations can only partly reveal.…”

Section: Commentarymentioning

confidence: 99%

Multi‐Photon Microscopy

Sanderson

2023

Current Protocols

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In this series of papers on light microscopy imaging, we have covered the fundamentals of microscopy, super-resolution microscopy, and lightsheet microscopy. This last review covers multi-photon microscopy with a brief reference to intravital imaging and Brainbow labeling. Multi-photon microscopy is often referred to as two-photon microscopy. Indeed, using two-photon microscopy is by far the most common way of imaging thick tissues; however, it is theoretically possible to use a higher number of photons, and three-photon microscopy is possible. Therefore, this review is titled "multi-photon microscopy." Another term for describing multi-photon microscopy is "non-linear" microscopy because fluorescence intensity at the focal spot depends upon the average squared intensity rather than the squared average intensity; hence, non-linear optics (NLO) is an alternative name for multi-photon microscopy. It is this non-linear relationship (or third exponential power in the case of three-photon excitation) that determines the axial optical sectioning capability of multi-photon imaging. In this paper, the necessity for two-photon or multi-photon imaging is explained, and the method of optical sectioning by multi-photon microscopy is described. Advice is also given on what fluorescent markers to use and other practical aspects of imaging thick tissues. The technique of Brainbow imaging is discussed. The review concludes with a description of intravital imaging of the mouse.

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3D imaging for driving cancer discovery

Cited by 9 publications

References 227 publications

Completing the view – histologic insights from circular AAA specimen including 3D imaging

Completing the view – histologic insights from circular AAA specimen including 3D imaging

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma

Multi‐Photon Microscopy

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