A review of artifacts in histopathology

Taqi, Syed Ahmed; Sami, Syed Abdus; Sami, Lateef Begum; Zaki, Syed Ahmed

doi:10.4103/jomfp.jomfp_125_15

Cited by 160 publications

(138 citation statements)

References 14 publications

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“…EPI-induced dermal skin structure disruption was visualized by EVCM images and histological sections, although with a slightly different presentation. The distinction could be explained by tissue alterations due to slow freezing, biopsy storage at −80℃, and tissue processing, which may have stretched the fragile tissue, exposing fragmented collagen and tissue gaps on histological sections [17]. Skin structure disruption of the dermis plays an important role in long-term effects of treatments focusing on skin remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, cryosections can be used to inspect the cutaneous microstructure. The proneness to artifacts and inherent need for a multistep staining procedure to achieve sufficient image contrast, however, supports the use of novel optical imaging techniques to supplement traditional histology when assessing novel drug delivery techniques [17]. Fluorescence confocal microscopy can overcome these limitations by visualizing immediate EPI-induced fluorescent drug distribution without destructive tissue preparation or additional staining steps.…”

Section: Introductionmentioning

confidence: 99%

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Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

et al. 2020

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Background and Objectives: Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI. Study Design/Materials and Methods: Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin-stained cryosections. Results: The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen. Conclusions: This is the first study to relate a reproducible clinical endpoint to EPI-assisted immediate drug delivery using EVCM. An EPI-induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

et al. 2020

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“…Fluorescence-based techniques have also been exploited to characterize the cellular and subcellular structures, both in healthy and pathological tissues. However, these techniques are characterized by some severe drawbacks: extensive tissue manipulation that can lead to artifacts, expensive and time consuming labeling protocols, lack of 3D sectioning, and, most important, delay in obtaining the diagnosis and interpretative variability (3–5).…”

Section: Introductionmentioning

confidence: 99%

Whole-Section Tumor Micro-Architecture Analysis by a Two-Dimensional Phasor-Based Approach Applied to Polarization-Dependent Second Harmonic Imaging

et al. 2019

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Second Harmonic Generation (SHG) microscopy has gained much interest in the histopathology field since it allows label-free imaging of tissues simultaneously providing information on their morphology and on the collagen microarchitecture, thereby highlighting the onset of pathologies and diseases. A wide request of image analysis tools is growing, with the aim to increase the reliability of the analysis of the huge amount of acquired data and to assist pathologists in a user-independent way during their diagnosis. In this light, we exploit here a set of phasor-parameters that, coupled to a 2-dimensional phasor-based approach (μMAPPS, Microscopic Multiparametric Analysis by Phasor projection of Polarization-dependent SHG signal) and a clustering algorithm, allow to automatically recover different collagen microarchitectures in the tissues extracellular matrix. The collagen fibrils microscopic parameters (orientation and anisotropy) are analyzed at a mesoscopic level by quantifying their local spatial heterogeneity in histopathology sections (few mm in size) from two cancer xenografts in mice, in order to maximally discriminate different collagen organizations, allowing in this case to identify the tumor area with respect to the surrounding skin tissue. We show that the “fibril entropy” parameter, which describes the tissue order on a selected spatial scale, is the most effective in enlightening the tumor edges, opening the possibility of their automatic segmentation. Our method, therefore, combined with tissue morphology information, has the potential to become a support to standard histopathology in diseases diagnosis.

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“…This process, which involves gross organ dissection, selection and preparation of tissue blocks for slide creation, microtomy (cutting and tissue placement on the slide), staining, and cover slipping, is fraught with multiple preanalytic opportunities for the introduction of artefacts and batch effects. 1–3 These artefacts may include improper tissue placement (eg, folding, compressing, tearing, air bubbles), improper reagents (eg, over- or under-staining, stain concentration differences, stain batch variation), and poor microtomy (eg, knife chatter, thickness variances). The increasingly popular digitization of these same slides, to take advantage of computational-aided diagnostic approaches, 4–6 for example, introduces yet another potential source of artefacts.…”

Section: Introductionmentioning

confidence: 99%

HistoQC: An Open-Source Quality Control Tool for Digital Pathology Slides

Janowczyk

Zuo

Gilmore

et al. 2019

JCO Clinical Cancer Informatics

223

175

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PURPOSE Digital pathology (DP), referring to the digitization of tissue slides, is beginning to change the landscape of clinical diagnostic workflows and has engendered active research within the area of computational pathology. One of the challenges in DP is the presence of artefacts and batch effects, unintentionally introduced during both routine slide preparation (eg, staining, tissue folding) and digitization (eg, blurriness, variations in contrast and hue). Manual review of glass and digital slides is laborious, qualitative, and subject to intra- and inter-reader variability. Therefore, there is a critical need for a reproducible automated approach of precisely localizing artefacts to identify slides that need to be reproduced or regions that should be avoided during computational analysis. METHODS Here we present HistoQC, a tool for rapidly performing quality control to not only identify and delineate artefacts but also discover cohort-level outliers (eg, slides stained darker or lighter than others in the cohort). This open-source tool employs a combination of image metrics (eg, color histograms, brightness, contrast), features (eg, edge detectors), and supervised classifiers (eg, pen detection) to identify artefact-free regions on digitized slides. These regions and metrics are presented to the user via an interactive graphical user interface, facilitating artefact detection through real-time visualization and filtering. These same metrics afford users the opportunity to explicitly define acceptable tolerances for their workflows. RESULTS The output of HistoQC on 450 slides from The Cancer Genome Atlas was reviewed by two pathologists and found to be suitable for computational analysis more than 95% of the time. CONCLUSION These results suggest that HistoQC could provide an automated, quantifiable, quality control process for identifying artefacts and measuring slide quality, in turn helping to improve both the repeatability and robustness of DP workflows.

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A review of artifacts in histopathology

Cited by 160 publications

References 14 publications

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

Whole-Section Tumor Micro-Architecture Analysis by a Two-Dimensional Phasor-Based Approach Applied to Polarization-Dependent Second Harmonic Imaging

HistoQC: An Open-Source Quality Control Tool for Digital Pathology Slides

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