Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies
Intraoperative 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 req...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/128835 |
| _version_ | 1811086805036957696 |
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| author | Cahill, Lucas Christopher Wu, Yubo Yoshitake, Tadayuki Ponchiardi, Cecilia Giacomelli, Michael Wagner, Andrew A. Rosen, Seymour Fujimoto, James G |
| author2 | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science |
| author_facet | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Cahill, Lucas Christopher Wu, Yubo Yoshitake, Tadayuki Ponchiardi, Cecilia Giacomelli, Michael Wagner, Andrew A. Rosen, Seymour Fujimoto, James G |
| author_sort | Cahill, Lucas Christopher |
| collection | MIT |
| description | Intraoperative 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. |
| first_indexed | 2024-09-23T13:34:57Z |
| format | Article |
| id | mit-1721.1/128835 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:34:57Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1288352022-10-01T15:50:20Z Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies Cahill, Lucas Christopher Wu, Yubo Yoshitake, Tadayuki Ponchiardi, Cecilia Giacomelli, Michael Wagner, Andrew A. Rosen, Seymour Fujimoto, James G Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Harvard University--MIT Division of Health Sciences and Technology Intraoperative 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. National Institutes of Health (Grants R01-CA178636-05, R01-CA075289-20, F32-CA183400-02) Air Force Office of Scientific Research (Contracts FA9550-12-1-0551 and FA9550-15-1-0473) 2020-12-15T21:26:55Z 2020-12-15T21:26:55Z 2019-11 2019-10 2020-12-11T19:53:45Z Article http://purl.org/eprint/type/JournalArticle 0893-3952 1530-0285 https://hdl.handle.net/1721.1/128835 Cahill, 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 http://dx.doi.org/10.1038/s41379-019-0408-4 Modern Pathology Article 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. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Cahill, Lucas Christopher Wu, Yubo Yoshitake, Tadayuki Ponchiardi, Cecilia Giacomelli, Michael Wagner, Andrew A. Rosen, Seymour Fujimoto, James G Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title | Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title_full | Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title_fullStr | Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title_full_unstemmed | Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title_short | Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies |
| title_sort | nonlinear microscopy for detection of prostate cancer analysis of sensitivity and specificity in radical prostatectomies |
| url | https://hdl.handle.net/1721.1/128835 |
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