Ex Vivo Confocal Fluorescence Microscopy for Rapid Evaluation of Tissues in Surgical Pathology Practice

Krishnamurthy, Savitri; Cortés, Andrea; Lopez, Mirtha S.; Wallace, Michael B.; Sabir, S.; Shaw, Kenna Mills; Mills, Gordon B.

doi:10.5858/arpa.2017-0164-oa

Cited by 38 publications

(33 citation statements)

References 36 publications

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“…In the 1980's, Tejada et al developed a specialized test with sperm AO fluorescence staining to determine male fertility (31). Krishnamurthy et al showed that staining of breast, lung, kidney, and liver tissues with AO alone and subsequent imaging with confocal laser microscopy practically does not differ in efficiency from staining with H&E (32). Moreover, AO staining was much faster and easier than H&E (32).…”

Section: Resultsmentioning

confidence: 99%

“…Krishnamurthy et al showed that staining of breast, lung, kidney, and liver tissues with AO alone and subsequent imaging with confocal laser microscopy practically does not differ in efficiency from staining with H&E (32). Moreover, AO staining was much faster and easier than H&E (32). In yet another application, Wang et al used AO for rapid non-destructive imaging of whole prostate biopsies using video-rate fluorescence structured illumination microscopy and demonstrated its feasibility as an alternative to destructive pathology (33).…”

Section: Resultsmentioning

confidence: 99%

“…AO fluorescence allowed for better tailoring of the resection area while maintaining the maximum amount of healthy tissue. This technology was used to remove breast tumors (35), soft tissue tumors and sarcomas (26, 44, 45), treatment of skin cancer (34, 46), conjunctival tumors (47), renal tumors, lungs, liver (32).…”

Section: Resultsmentioning

confidence: 99%

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Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

et al. 2019

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Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy.Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term “acridine orange” with the following: “surgical oncology,” “neuropathology,” “microsurgery,” “intraoperative fluorescence,” “confocal microscopy,” “pathology,” “endomicroscopy,” “guidance,” “fluorescence guidance,” “oncology,” “surgery,” “neurooncology,” and “photodynamic therapy.” Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles.Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy.Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

et al. 2019

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“…A comprehensive list of potential EVM applications was developed from a review of the published literature performed as part of the annual update of the CAP IVM Resource Guide, as well as from expert opinion within the group. 7,[9][10][11][12][13] Three EVM applications were then selected for development of detailed FRs based on currently published studies and likely wide use in pathology practice. The FR categories were formulated to encompass the requirements for pathology practice and compliance with applicable guidelines and regulations.…”

Section: Designmentioning

confidence: 99%

“…The consensus opinion was that EVM systems should have resolution comparable to a magnification of 310 to 320 (0.5-1.0 lm resolution) in a standard light microscope. 7 This should be sufficient to assess tissue adequacy for diagnosis or to identify lesional tissue for special studies or biorepository, including assessing cellularity and viability. For margin assessment, healthy or benign tissue should be able to be distinguished from malignant (invasive or in situ cancer).…”

Section: Evm Functional Requirementsmentioning

confidence: 99%

Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists

Mathur

Fitzmaurice

Reder

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— In vivo microscopy (IVM) allows direct, real-time visualization of tissue histology in living patients without the need for tissue removal, processing, or staining. The IVM technologies in clinical use include confocal microscopy and optical coherence tomography. These technologies also show promise for use with pathology specimens (ex vivo microscopy [EVM]). However, few systems designed for EVM are commercially available, at least in part because of the lack of defined minimal functional requirements (FRs). Objective.— To develop minimal FRs for likely high-volume pathology applications of EVM. Design.— The IVM Committee of the College of American Pathologists identified potential EVM pathology applications based on the published literature. A subcommittee of IVM and EVM early adopters and experts then defined FRs for the most likely EVM applications. Results.— Potential EVM applications include assessment of margins, adequacy of needle biopsies and aspirates for diagnosis, and transplant tissues; selection of tissue for molecular studies or biorepository; and guidance in block selection from gross specimens. The first 3 applications were selected for development of FRs. The FRs were identified based on existing laboratory practices and guidelines and input from experts in the field and included device footprint and portability, specimen preparation, imaging time, field of view or resolution, morphologic diagnostic capability, yield, accuracy, ease of use, safety, and cost. Conclusions.— Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.

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Comparison of Real-Time Fluorescence Confocal Digital Microscopy With Hematoxylin-Eosin–Stained Sections of Core-Needle Biopsy Specimens

et al. 2020

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IMPORTANCE Strategies to procure high-quality core-needle biopsy (CNB) specimens are critical for making basic tissue diagnoses and for ancillary testing. OBJECTIVES To investigate acquisition of fluorescence confocal microscopy (FCM) images of interventional radiology (IR)-guided CNB in real time in the radiology suite and to compare the accuracy of FCM diagnoses with those of hematoxylin-eosin (H&E)-stained CNB sections. DESIGN, SETTING, AND PARTICIPANTS In this diagnostic study, FCM imaging of IR-guided CNBs was performed in the radiology suite at a major cancer center for patients with an imaging abnormality from August 1, 2016, to April 30, 2019. The time taken to acquire FCM images and the quality of FCM images based on percentage of interpretable tissue with optimal resolution was recorded. The FCM images were read by 2 pathologists and categorized as nondiagnostic, benign/ atypical, or suspicious/malignant; these diagnoses were compared with those made using H&E-stained tissue sections. Cases with discrepant diagnosis were reassessed by the pathologists together for a consensus diagnosis. Data were analyzed from June 3 to July 19, 2019. INTERVENTIONS Each IR-guided CNB was stained with 0.6mM acridine orange, subjected to FCM imaging, and then processed to generate H&E-stained sections. MAIN OUTCOMES AND MEASURES Mean time taken for acquisition of FCM images, quality of FCM images based on interpretable percentage of the image, and accuracy of diagnostic categorization based on FCM images compared with H&E-stained sections. RESULTS A total of 105 patients (57 male [54.3%]; mean [SD] age, 63 [13] years) underwent IR-guided CNBs in a mean (SD) of 7 (2) minutes each. The FCM images showed at least 20% of the tissue with optimal quality in 101 CNB specimens (96.2%). The FCM images were accurately interpreted by the 2 pathologists in 100 of 105 cases (95.2%) (2 false-positive and 3 false-negative) and 90 of 105 cases (85.7%) (6 false-positive and 9 false-negative). A reassessment of 14 discordant diagnoses resulted in consensus diagnoses that were accurate in 101 of 105 cases (96.2%) (1 falsepositive and 3 false-negative). CONCLUSIONS AND RELEVANCE The ease of acquisition of FCM images of acceptable quality and the high accuracy of the diagnoses suggest that FCM may be useful for rapid evaluation of IR-guided CNBs. This approach warrants further investigation.

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Ex Vivo Confocal Fluorescence Microscopy for Rapid Evaluation of Tissues in Surgical Pathology Practice

Abstract: - The ease and speed of acquisition of CFM images together with the resolution and resemblance of the CFM images to hematoxylin-eosin sections suggest that the CFM platform has excellent potential for use in surgical pathology practice.

Cited by 38 publications

References 36 publications

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists

Comparison of Real-Time Fluorescence Confocal Digital Microscopy With Hematoxylin-Eosin–Stained Sections of Core-Needle Biopsy Specimens

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