Maximizing content across scales: Moving multimodal microscopy and mesoscopy toward molecular imaging

Munck, Sebastian; Swoger, Jim; Coll-Lladó, Montserrat; Gritti, Nicola; Velde, Greetje Vande

doi:10.1016/j.cbpa.2021.05.003

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…Given the similarity of correction between the OPTiSPIM and medical imaging approaches, we thought it worthwhile to look closer at how correction is carried out in medical imaging, and the underlying foundations. Next to corrections, the potential for connecting mesoscale and medical imaging for multimodal imaging has been highlighted recently 107 …”

Section: Strategies From Medical Imagingmentioning

confidence: 99%

“…Next to corrections, the potential for connecting mesoscale and medical imaging for multimodal imaging has been highlighted recently. 107 Tomography, the generation of cross-sectional images via the acquisition of projection data of a penetrating wave/particle, is well established in a range of medical imaging techniques that have now found application at the mesoscale. Conceptually, emission tomography is similar to fluorescence microscopy in the sense that images are created from photons that are emitted from the sample.…”

Section: Strategies From Medical Imagingmentioning

confidence: 99%

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Challenges and advances in optical 3D mesoscale imaging

Munck

Cawthorne

Escamilla-Ayala

et al. 2022

Journal of Microscopy

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Optical mesoscale imaging is a rapidly developing field that allows the visualisation of larger samples than is possible with standard light microscopy, and fills a gap between cell and organism resolution. It spans from advanced fluorescence imaging of micrometric cell clusters to centimetre-size complete organisms.However, with larger volume specimens, new problems arise. Imaging deeper into tissues at high resolution poses challenges ranging from optical distortions to shadowing from opaque structures. This manuscript discusses the latest developments in mesoscale imaging and highlights limitations, namely labelling, clearing, absorption, scattering, and also sample handling. We then focus on approaches that seek to turn mesoscale imaging into a more quantitative technique, analogous to quantitative tomography in medical imaging, highlighting a future role for digital and physical phantoms as well as artificial intelligence.

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Section: Strategies From Medical Imagingmentioning

confidence: 99%

Section: Strategies From Medical Imagingmentioning

confidence: 99%

Challenges and advances in optical 3D mesoscale imaging

Munck

Cawthorne

Escamilla-Ayala

et al. 2022

Journal of Microscopy

Self Cite

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“…The complex 3D structure of the human brain is inherently multiscale and exists of very small structures that extend over large distances, even entire brain areas 1 . The layered cortical cytoarchitecture, for instance, is defined by cellular density, size, and morphology at the microscopic scale, but its layers extend over entire cortical areas and hence layering occurs over centimetre scales.…”

Section: Introductionmentioning

confidence: 99%

Efficient 3D light-sheet imaging of very large-scale optically cleared human brain and prostate tissue samples

et al. 2023

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The ability to image human tissue samples in 3D, with both cellular resolution and a large field of view (FOV), can improve fundamental and clinical investigations. Here, we demonstrate the feasibility of light-sheet imaging of ~5 cm3 sized formalin fixed human brain and up to ~7 cm3 sized formalin fixed paraffin embedded (FFPE) prostate cancer samples, processed with the FFPE-MASH protocol. We present a light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), capable of fast 3D high-resolution acquisitions of cm3 scale cleared tissue. We used mosaic scans for fast 3D overviews of entire tissue samples or higher resolution overviews of large ROIs with various speeds: (a) Mosaic 16 (16.4 µm isotropic resolution, ~1.7 h/cm3), (b) Mosaic 4 (4.1 µm isotropic resolution, ~ 5 h/cm3) and (c) Mosaic 0.5 (0.5 µm near isotropic resolution, ~15.8 h/cm3). We could visualise cortical layers and neurons around the border of human brain areas V1&V2, and could demonstrate suitable imaging quality for Gleason score grading in thick prostate cancer samples. We show that ct-dSPIM imaging is an excellent technique to quantitatively assess entire MASH prepared large-scale human tissue samples in 3D, with considerable future clinical potential.

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“…Volumetric optical mesoscopic imaging, which bridges the gap between microscopy and macrophotography, offers a possible solution to overcome these technical limitations. There exist several mesoscale imaging technologies (Munck et al, 2021), but for studying whole mouse brain architecture with high spatial resolution in three dimensions the Mesolens is the ideal objective lens. It is a giant multi-element lens with high numerical aperture (0.47) and low magnification (4x) and achieves three-dimensional imaging with 700 nm lateral resolution and 4 µm axial resolution in a volume of capture exceeding 100 mm 3 (McConnell et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Application of light-sheet mesoscopy to image host-pathogen interactions in intact organs

Battistella

Quintana

McConnell

2022

Preprint

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Human African Trypanosomiasis (HAT) is a disease caused by the extracellular parasite Trypanosoma brucei that affects the central nervous system (CNS) during the chronic stage of the infection, inducing neuroinflammation, coma, and death if left untreated. However, little is known about the structural change happening in the brain as result of the infection. So far, infection-induced neuroinflammation has been observed with conventional methods, such as immunohistochemistry, electron microscopy, and 2-photon microscopy only in small portions of the brain, which may not be representative of the disease. In this paper, we have used a newly-developed light-sheet illuminator to image the level of neuroinflammation in chronically infected mice and we use analyse these data to compare the infection in na&iumlve controls. This system was developed for imaging in combination with the Mesolens objective lens, providing sub-cellular resolution for imaging volumes exceeding 39 mm3 in an acquisition time of only 8 hours. The mouse brain specimens were cleared using CUBIC+, followed by antibody staining to locate Glial Fibrillary Acid Protein (GFAP) expressing cells, primarily astrocytes and ependymocytes, used here as a proxy for cell reactivity and gliosis. The large capture volume allowed us to detect GFAP+ cells and spatially resolve the innate responses to T. brucei infection. Based on morphometric analyses and spatial distribution of GFAP+ cells, our data demonstrates a significant increase in cell dendrite branching around the lateral ventricle, as well as dorsal and ventral third ventricles, that are negatively correlated with the branch extension in distal sites from the circumventricular spaces. To our knowledge, this is the first report highlighting the potential of light sheet mesoscopy to characterise the inflammatory responses of the mouse brain to parasitic infection at the cellular level in intact cleared organs, opening new avenues for the development of new mesoscale imaging techniques for the study of host-pathogen interactions.

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Maximizing content across scales: Moving multimodal microscopy and mesoscopy toward molecular imaging

Cited by 8 publications

References 65 publications

Challenges and advances in optical 3D mesoscale imaging

Challenges and advances in optical 3D mesoscale imaging

Efficient 3D light-sheet imaging of very large-scale optically cleared human brain and prostate tissue samples

Application of light-sheet mesoscopy to image host-pathogen interactions in intact organs

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