A bigger and better picture of clinical samples

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Science Translational Medicine  23 Aug 2017:
Vol. 9, Issue 404, eaao4209
DOI: 10.1126/scitranslmed.aao4209


An open-top light-sheet microscope enables rapid high-resolution panoramic imaging of intact clinical samples to increase the accuracy and reproducibility of clinical histology.

Microscopic examination of a tissue biopsy or surgical specimen has been the gold standard for cancer diagnosis and treatment decisions. Conventional histology, however, involves laborious, time-consuming processes, requiring multiple pathology lab instruments to formalin-fix, dehydrate, paraffin-embed, slice, and stain tissue samples. Frozen sectioning bypasses the chemical fixation and paraffin-embedding steps, allowing rapid processing, but severe artifacts can be introduced during tissue freezing. For both methods, relatively few of the sections produced by slicing are often mounted on glass slides and imaged. The resulting sparse sampling and loss of volumetric information limits diagnostic accuracy and reproducibility. Overcoming the shortcomings of traditional histology could decrease healthcare costs and improve patient care.

In a new study, Glaser et al. developed an open-top light-sheet microscopy system that enables rapid, nondestructive imaging of intact clinical specimens. Tissue samples are placed directly on the microscope’s large glass plate, thus obviating the need to prepare histology slides. Two orthogonally arranged objectives located underneath the plate generate a thin plane of light that rapidly scan the sample and collect the photons emitted from the samples. This system allows rapid diffraction-limited panoramic imaging of tissues of arbitrary size and thickness.

The researchers used this system to diagnose surgically excised breast tumor tissues intraoperatively. A conventional intraoperative pathology consultation would have required frozen sectioning to deliver a diagnosis within 20 min. Frozen sectioning would have yielded sparse tissue sampling and tissue could become damaged during the freezing process, potentially leading to inaccurate diagnosis. In contrast, the new microscopy system enabled the researchers to image the entire excised tissue’s surface within only 1 min, after minimal processing. The acquired digitized data provided both a panoramic view of the total tissue surface and high-resolution views of relevant breast pathologies.

When combined with the CLARITY method, which optically clears intact tissues to render them translucent, the system allowed rapid volumetric imaging of a core-needle prostate biopsy. The added three-dimensional tissue context minimized the artifacts of tangential sectioning and improved the accuracy of the grading of the biopsy. However, the authors extracted lipids from the tissues to clear them, without the addition of supporting hydrogel, which could have resulted in tissue damage. In addition, although faster than conventional histology, clearing and labeling an intact biopsy sample limits the approach’s throughput. Aside from these considerations, this easy-to-use, versatile light-sheet microscopy method possesses transformative potential to improve tissue diagnosis and patient treatments.

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