TY - INPR A1 - Aubreville, Marc A1 - Stathonikos, Nikolas A1 - Donovan, Taryn A1 - Klopfleisch, Robert A1 - Ganz, Jonathan A1 - Ammeling, Jonas A1 - Wilm, Frauke A1 - Veta, Mitko A1 - Jabari, Samir A1 - Eckstein, Markus A1 - Annuscheit, Jonas A1 - Krumnow, Christian A1 - Bozaba, Engin A1 - Cayir, Sercan A1 - Gu, Hongyan A1 - Chen, Xiang A1 - Jahanifar, Mostafa A1 - Shephard, Adam A1 - Kondo, Satoshi A1 - Kasai, Satoshi A1 - Kotte, Sujatha A1 - Saipradeep, Vangala A1 - Lafarge, Maxime W. A1 - Koelzer, Viktor H. A1 - Wang, Ziyue A1 - Zhang, Yongbing A1 - Yang, Sen A1 - Wang, Xiyue A1 - Breininger, Katharina A1 - Bertram, Christof T1 - Domain generalization across tumor types, laboratories, and species – Insights from the 2022 edition of the Mitosis Domain Generalization Challenge N2 - Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an F1 score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking. UR - https://doi.org/10.48550/arXiv.2309.15589 Y1 - 2023 UR - https://doi.org/10.48550/arXiv.2309.15589 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-41514 PB - arXiv CY - Ithaca ER - TY - JOUR A1 - Sievert, Matti A1 - Oetter, Nicolai A1 - Aubreville, Marc A1 - Stelzle, Florian A1 - Maier, Andreas A1 - Eckstein, Markus A1 - Mantsopoulos, Konstantinos A1 - Gostian, Antoniu-Oreste A1 - Müller, Sarina K. A1 - Koch, Michael A1 - Agaimy, Abbas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Feasibility of intraoperative assessment of safe surgical margins during laryngectomy with confocal laser endomicroscopy BT - a pilot study JF - Auris Nasus Larynx UR - https://doi.org/10.1016/j.anl.2021.01.005 Y1 - 2021 UR - https://doi.org/10.1016/j.anl.2021.01.005 SN - 1879-1476 VL - 48 IS - 4 SP - 764 EP - 769 PB - Elsevier Science CY - Amsterdam ER - TY - JOUR A1 - Sievert, Matti A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Eckstein, Markus A1 - Rupp, Robin A1 - Aubreville, Marc A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Systematic interpretation of confocal laser endomicroscopy: larynx and pharynx confocal imaging score JF - Acta otorhinolaryngologica italica N2 - Objective. Development and validation of a confocal laser endomicroscopy (CLE) classification score for the larynx and pharynx. Methods. Thirteen patients (154 video sequences, 9240 images) with laryngeal or pharyngeal SCC were included in this prospective study between October 2020 and February 2021. Each CLE sequence was correlated with the gold standard of histopathological examination. Based on a dataset of 94 video sequences (5640 images), a scoring system was developed. In the remaining 60 sequences (3600 images), the score was validated by four CLE experts and four head and neck surgeons who were not familiar with CLE. Results. Tissue homogeneity, cell size, borders and clusters, capillary loops and the nucleus/ cytoplasm ratio were defined as the scoring criteria. Using this score, the CLE experts obtained an accuracy, sensitivity, and specificity of 90.8%, 95.1%, and 86.4%, respectively, and the CLE non-experts of 86.2%, 86.4%, and 86.1%. Interobserver agreement Fleiss’ kappa was 0.8 and 0.6, respectively. Conclusions. CLE can be reliably evaluated based on defined and reproducible imaging features, which demonstrate a high diagnostic value. CLE can be easily integrated into the intraoperative setting and generate real-time, in-vivo microscopic images to demarcate malignant changes. UR - https://doi.org/10.14639/0392-100X-N1643 KW - confocal laser endomicroscopy KW - head and neck cancer KW - classification system KW - non-invasive histological imaging KW - larynx KW - pharynx Y1 - 2022 UR - https://doi.org/10.14639/0392-100X-N1643 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-29175 SN - 1827-675X VL - 42 IS - 1 SP - 26 EP - 33 PB - Pacini CY - Pisa ER - TY - JOUR A1 - Aubreville, Marc A1 - Stathonikos, Nikolas A1 - Donovan, Taryn A1 - Klopfleisch, Robert A1 - Ammeling, Jonas A1 - Ganz, Jonathan A1 - Wilm, Frauke A1 - Veta, Mitko A1 - Jabari, Samir A1 - Eckstein, Markus A1 - Annuscheit, Jonas A1 - Krumnow, Christian A1 - Bozaba, Engin A1 - Cayir, Sercan A1 - Gu, Hongyan A1 - Chen, Xiang A1 - Jahanifar, Mostafa A1 - Shephard, Adam A1 - Kondo, Satoshi A1 - Kasai, Satoshi A1 - Kotte, Sujatha A1 - Saipradeep, Vangala A1 - Lafarge, Maxime W. A1 - Koelzer, Viktor H. A1 - Wang, Ziyue A1 - Zhang, Yongbing A1 - Yang, Sen A1 - Wang, Xiyue A1 - Breininger, Katharina A1 - Bertram, Christof T1 - Domain generalization across tumor types, laboratories, and species — Insights from the 2022 edition of the Mitosis Domain Generalization Challenge JF - Medical Image Analysis N2 - Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert majority vote and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today’s deep learning-based recognition pipelines. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, with only minor changes in the order of participants in the ranking. UR - https://doi.org/10.1016/j.media.2024.103155 Y1 - 2024 UR - https://doi.org/10.1016/j.media.2024.103155 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-58479 SN - 1361-8423 VL - 2024 IS - 94 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Sievert, Matti A1 - Aubreville, Marc A1 - Mueller, Sarina Katrin A1 - Eckstein, Markus A1 - Breininger, Katharina A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Diagnosis of malignancy in oropharyngeal confocal laser endomicroscopy using GPT 4.0 with vision JF - European Archives of Oto-Rhino-Laryngology UR - https://doi.org/10.1007/s00405-024-08476-5 Y1 - 2024 UR - https://doi.org/10.1007/s00405-024-08476-5 SN - 1434-4726 SN - 0937-4477 VL - 281 IS - 4 SP - 2115 EP - 2122 PB - Springer CY - Berlin ER - TY - JOUR A1 - Sievert, Matti A1 - Aubreville, Marc A1 - Gostian, Antoniu-Oreste A1 - Mantsopoulos, Konstantinos A1 - Koch, Michael A1 - Müller, Sarina K. A1 - Eckstein, Markus A1 - Rupp, Robin A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Validity of tissue homogeneity in confocal laser endomicroscopy on the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma JF - European Archives of Oto-Rhino-Laryngology and Head & Neck N2 - Purpose Confocal laser endomicroscopy (CLE) allows imaging of the laryngeal mucosa in a thousand-fold magnification. This study analyzes differences in tissue homogeneity between healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included five SCC patients with planned total laryngectomy in this study between October 2020 and February 2021. We captured CLE scans of the tumor and healthy mucosa. Analysis of image homogeneity to diagnose SCC was performed by measuring the signal intensity in four regions of interest (ROI) in each frame in a total of 60 sequences. Each sequence was assigned to the corresponding histological pattern, derived from hematoxylin and eosin staining. In addition, we recorded the subjective evaluation of seven investigators regarding tissue homogeneity. Results Out of 3600 images, 1620 (45%) correlated with benign mucosa and 1980 (55%) with SCC. ROIs of benign mucosa and SCC had a mean and standard deviation (SD) of signal intensity of, respectively, 232.1 ± 3.34 and 467.3 ± 9.72 (P < 0.001). The mean SD between the four different ROIs was 39.1 ± 1.03 for benign and 101.5 ± 2.6 for SCC frames (P < 0.001). In addition, homogeneity yielded a sensitivity and specificity of 81.8% and 86.2%, respectively, regarding the investigator-dependent analysis. Conclusions SCC shows a significant tissue inhomogeneity in comparison to the healthy epithelium. The results support this feature’s importance in identifying malignant mucosa areas during CLE examination. However, the examiner-dependent evaluation emphasizes that homogeneity is a sub-criterion that must be considered in a broad context. UR - https://doi.org/10.1007/s00405-022-07304-y KW - confocal laser endomicroscopy KW - head and neck cancer KW - classification system KW - non-invasive histological imaging KW - larynx KW - pharynx Y1 - 2022 UR - https://doi.org/10.1007/s00405-022-07304-y UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-23180 SN - 1434-4726 SN - 0937-4477 VL - 279 IS - 8 SP - 4147 EP - 4156 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Sievert, Matti A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Rupp, Robin A1 - Eckstein, Markus A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Validation of a classification and scoring system for the diagnosis of laryngeal and pharyngeal squamous cell carcinomas by confocal laser endomicroscopy JF - Brazilian Journal of Otorhinolaryngology N2 - Introduction Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract’s mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. Objective This study aims to validate an eight-point score for the correct assessment of malignancy. Methods We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. Results Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. Conclusion The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis. UR - https://doi.org/10.1016/j.bjorl.2021.06.002 KW - confocal laser endomicroscopy KW - squamous cell carcinoma KW - head and neck cancer KW - diagnosis Y1 - 2021 UR - https://doi.org/10.1016/j.bjorl.2021.06.002 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-20887 SN - 1808-8694 VL - 2022 IS - 88, S4 SP - 26 EP - 32 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Sievert, Matti A1 - Eckstein, Markus A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Stelzle, Florian A1 - Aubreville, Marc A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma JF - European Archives of Oto-Rhino-Laryngology and Head & Neck N2 - Purpose Confocal laser endomicroscopy (CLE) allows surface imaging of the laryngeal and pharyngeal mucosa in vivo at a thousand-fold magnification. This study aims to compare irregular blood vessels and intraepithelial capillary loops in healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included ten patients with confirmed SCC and planned total laryngectomy in this study between March 2020 and February 2021. CLE images of these patients were collected and compared with the corresponding histology in hematoxylin and eosin staining. We analyzed the characteristic endomicroscopic patterns of blood vessels and intraepithelial capillary loops for the diagnosis of SCC. Results In a total of 54 sequences, we identified 243 blood vessels which were analyzed regarding structure, diameter, and Fluorescein leakage, confirming that irregular, corkscrew-like vessels (24.4% vs. 1.3%; P < .001), dilated intraepithelial capillary loops (90.8% vs. 28.7%; P < .001), and increased capillary leakage (40.7% vs. 2.5%; P < .001), are significantly more frequently detected in SCC compared to the healthy epithelium. We defined a vessel diameter of 30 μm in capillary loops as a cut-off value, obtaining a sensitivity, specificity, PPV, and NPV and accuracy of 90.6%, 71.3%, 57.4%, 94.7%, and 77.1%, respectively, for the detection of malignancy based solely on capillary architecture. Conclusion Capillaries within malignant lesions are fundamentally different from those in healthy mucosa regions. The capillary architecture is a significant feature aiding the identification of malignant mucosa areas during in-vivo, real-time CLE examination. UR - https://doi.org/10.1007/s00405-021-06954-8 KW - confocal laser endomicroscopy KW - head and neck squamous cell carcinoma KW - capillary loops KW - malignant vascularization KW - head and neck malignancies Y1 - 2021 UR - https://doi.org/10.1007/s00405-021-06954-8 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-23196 SN - 1434-4726 SN - 0937-4477 VL - 279 IS - 4 SP - 2029 EP - 2037 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Sievert, Matti A1 - Stelzle, Florian A1 - Aubreville, Marc A1 - Müller, Sarina K. A1 - Eckstein, Markus A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Mantsopoulos, Konstantinos A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Intraoperative free margins assessment of oropharyngeal squamous cell carcinoma with confocal laser endomicroscopy: a pilot study JF - European Archives of Oto-Rhino-Laryngology and Head & Neck N2 - Purpose This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with confocal laser endomicroscopy (CLE) during oropharyngeal squamous cell carcinoma (OPSCC) surgery. Methods We included five consecutive patients confirmed OPSCC and planned tumor resection in September and October 2020. Healthy appearing mucosa in the marginal zone, and the tumor margin, were examined with CLE and biopsy during tumor resection. A total of 12,809 CLE frames were correlated with the gold standard of hematoxylin and eosin staining. Three head and neck surgeons and one pathologist were asked to identify carcinoma in a sample of 169 representative images, blinded to the histological results. Results Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of OPSCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 86%, 90%, 79%, 88%, and 82%, respectively, with inter-rater reliability and κ-value of 0.60. Conclusion CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the oropharynx for evaluation and demarcation of cancer. It can eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin. UR - https://doi.org/10.1007/s00405-021-06659-y KW - Confocal laser endomicroscopy KW - Oropharyngeal squamous cell carcinoma KW - Safe surgical margins KW - Head and neck malignancies Y1 - 2021 UR - https://doi.org/10.1007/s00405-021-06659-y UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-10914 SN - 1434-4726 SN - 0937-4477 VL - 278 IS - 11 SP - 4433 EP - 4439 PB - Springer Nature CY - Cham ER -