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dc.contributor.authorCahill, Lucas Christopher
dc.contributor.authorWu, Yubo
dc.contributor.authorYoshitake, Tadayuki
dc.contributor.authorPonchiardi, Cecilia
dc.contributor.authorGiacomelli, Michael
dc.contributor.authorWagner, Andrew A.
dc.contributor.authorRosen, Seymour
dc.contributor.authorFujimoto, James G
dc.date.accessioned2020-12-15T21:26:55Z
dc.date.available2020-12-15T21:26:55Z
dc.date.issued2019-11
dc.date.submitted2019-10
dc.identifier.issn0893-3952
dc.identifier.issn1530-0285
dc.identifier.urihttps://hdl.handle.net/1721.1/128835
dc.description.abstractIntraoperative evaluation of specimens during radical prostatectomy using frozen sections can be time and labor intensive. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can rapidly generate images that closely resemble H&E histology in freshly excised tissue, without requiring freezing or microtome sectioning. Specimens are stained with nuclear and cytoplasmic/stromal fluorophores, and NLM evaluation can begin within 3 min of grossing. Fluorescence signals can be displayed using an H&E color scale, facilitating pathologist interpretation. This study evaluates the accuracy of prostate cancer detection in a blinded reading of NLM images compared with the gold standard of formalin-fixed, paraffin-embedded H&E histology. A total of 122 freshly excised prostate specimens were obtained from 40 patients undergoing radical prostatectomy. The prostates were grossed, dissected into specimens of ~10 × 10 mm with 1–4 mm thickness, stained for 2 min for nuclear and cytoplasmic/stromal contrast, and then rinsed with saline for 30 s. NLM images were acquired and multiple images were stitched together to generate large field of view, centimeter-scale digital images suitable for reading. Specimens were then processed for standard paraffin H&E. The study protocol consisted of training, pretesting, and blinded reading phases. After a washout period, pathologists read corresponding paraffin H&E slides. Three pathologists achieved a 95% or greater sensitivity with 100% specificity for detecting cancer on NLM compared with paraffin H&E. Pooled sensitivity and specificity was 97.3% (93.7–99.1%; 95% confidence interval) and 100.0% (97.0–100.0%), respectively. Interobserver agreement for NLM reading had a Fleiss κ = 0.95. The high cancer detection accuracy and rapid specimen preparation suggest that NLM may be useful for intraoperative evaluation in radical prostatectomy.en_US
dc.description.sponsorshipNational Institutes of Health (Grants R01-CA178636-05, R01-CA075289-20, F32-CA183400-02)en_US
dc.description.sponsorshipAir Force Office of Scientific Research (Contracts FA9550-12-1-0551 and FA9550-15-1-0473)en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/s41379-019-0408-4en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleNonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomiesen_US
dc.typeArticleen_US
dc.identifier.citationCahill, Lucas C. et al. "Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies." 33, 5 (November 2019): 916–923 © 2019 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Research Laboratory of Electronicsen_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.relation.journalModern Pathologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-12-11T19:53:45Z
dspace.orderedauthorsCahill, LC; Wu, Y; Yoshitake, T; Ponchiardi, C; Giacomelli, MG; Wagner, AA; Rosen, S; Fujimoto, JGen_US
dspace.date.submission2020-12-11T19:53:49Z
mit.journal.volume33en_US
mit.journal.issue5en_US
mit.licensePUBLISHER_POLICY
mit.metadata.statusComplete


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