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1. Application of Novel PACS-based Informatics Platform to Identify Imaging Based Predictors of CDKN2A Allelic Status in Glioblastomas

Author

Tillmanns, Niklas, Lost, Jan, Tabor, Joanna, Vasandani, Sagar, Vetsa, Shaurey, Marianayagam, Neelan, Yalcin, Kanat, Erson-Omay, E. Zeynep, von Reppert, Marc, Jekel, Leon, Merkaj, Sara, Ramakrishnan, Divya, Avesta, Arman, Santo, Irene Dixe de Oliveira, Jin, Lan, Huttner, Anita, Bousabarah, Khaled, Ikuta, Ichiro, Lin, MingDe, Aneja, Sanjay, Turowski, Bernd, Aboian, Mariam, and Moliterno, Jennifer

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64% vs. 30%, p=0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI:1.5-12.1; p<0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status., Comment: 23 pages, 5 figures

Published
2023

2. The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI

Author

Moawad, Ahmed W., Janas, Anastasia, Baid, Ujjwal, Ramakrishnan, Divya, Saluja, Rachit, Ashraf, Nader, Jekel, Leon, Amiruddin, Raisa, Adewole, Maruf, Albrecht, Jake, Anazodo, Udunna, Aneja, Sanjay, Anwar, Syed Muhammad, Bergquist, Timothy, Calabrese, Evan, Chiang, Veronica, Chung, Verena, Conte, Gian Marco Marco, Dako, Farouk, Eddy, James, Ezhov, Ivan, Familiar, Ariana, Farahani, Keyvan, Iglesias, Juan Eugenio, Jiang, Zhifan, Johanson, Elaine, Kazerooni, Anahita Fathi, Kofler, Florian, Krantchev, Kiril, LaBella, Dominic, Van Leemput, Koen, Li, Hongwei Bran, Linguraru, Marius George, Link, Katherine E., Liu, Xinyang, Maleki, Nazanin, Meier, Zeke, Menze, Bjoern H, Moy, Harrison, Osenberg, Klara, Piraud, Marie, Reitman, Zachary, Shinohara, Russel Takeshi, Tahon, Nourel hoda, Nada, Ayman, Velichko, Yuri S., Wang, Chunhao, Wiestler, Benedikt, Wiggins, Walter, Shafique, Umber, Willms, Klara, Avesta, Arman, Bousabarah, Khaled, Chakrabarty, Satrajit, Gennaro, Nicolo, Holler, Wolfgang, Kaur, Manpreet, LaMontagne, Pamela, Lin, MingDe, Lost, Jan, Marcus, Daniel S., Maresca, Ryan, Merkaj, Sarah, Nada, Ayaman, Pedersen, Gabriel Cassinelli, von Reppert, Marc, Sotiras, Aristeidis, Teytelboym, Oleg, Tillmans, Niklas, Westerhoff, Malte, Youssef, Ayda, Godfrey, Devon, Floyd, Scott, Rauschecker, Andreas, Villanueva-Meyer, Javier, Pflüger, Irada, Cho, Jaeyoung, Bendszus, Martin, Brugnara, Gianluca, Cramer, Justin, Perez-Carillo, Gloria J. Guzman, Johnson, Derek R., Kam, Anthony, Kwan, Benjamin Yin Ming, Lai, Lillian, Lall, Neil U., Memon, Fatima, Patro, Satya Narayana, Petrovic, Bojan, So, Tiffany Y., Thompson, Gerard, Wu, Lei, Schrickel, E. Brooke, Bansal, Anu, Barkhof, Frederik, Besada, Cristina, Chu, Sammy, Druzgal, Jason, Dusoi, Alexandru, Farage, Luciano, Feltrin, Fabricio, Fong, Amy, Fung, Steve H., Gray, R. Ian, Ikuta, Ichiro, Iv, Michael, Postma, Alida A., Mahajan, Amit, Joyner, David, Krumpelman, Chase, Letourneau-Guillon, Laurent, Lincoln, Christie M., Maros, Mate E., Miller, Elka, Morón, Fanny, Nimchinsky, Esther A., Ozsarlak, Ozkan, Patel, Uresh, Rohatgi, Saurabh, Saha, Atin, Sayah, Anousheh, Schwartz, Eric D., Shih, Robert, Shiroishi, Mark S., Small, Juan E., Tanwar, Manoj, Valerie, Jewels, Weinberg, Brent D., White, Matthew L., Young, Robert, Zohrabian, Vahe M., Azizova, Aynur, Brüßeler, Melanie Maria Theresa, Fehringer, Pascal, Ghonim, Mohanad, Ghonim, Mohamed, Gkampenis, Athanasios, Okar, Abdullah, Pasquini, Luca, Sharifi, Yasaman, Singh, Gagandeep, Sollmann, Nico, Soumala, Theodora, Taherzadeh, Mahsa, Yordanov, Nikolay, Vollmuth, Philipp, Foltyn-Dumitru, Martha, Malhotra, Ajay, Abayazeed, Aly H., Dellepiane, Francesco, Lohmann, Philipp, Pérez-García, Víctor M., Elhalawani, Hesham, Al-Rubaiey, Sanaria, Armindo, Rui Duarte, Ashraf, Kholod, Asla, Moamen M., Badawy, Mohamed, Bisschop, Jeroen, Lomer, Nima Broomand, Bukatz, Jan, Chen, Jim, Cimflova, Petra, Corr, Felix, Crawley, Alexis, Deptula, Lisa, Elakhdar, Tasneem, Shawali, Islam H., Faghani, Shahriar, Frick, Alexandra, Gulati, Vaibhav, Haider, Muhammad Ammar, Hierro, Fátima, Dahl, Rasmus Holmboe, Jacobs, Sarah Maria, Hsieh, Kuang-chun Jim, Kandemirli, Sedat G., Kersting, Katharina, Kida, Laura, Kollia, Sofia, Koukoulithras, Ioannis, Li, Xiao, Abouelatta, Ahmed, Mansour, Aya, Maria-Zamfirescu, Ruxandra-Catrinel, Marsiglia, Marcela, Mateo-Camacho, Yohana Sarahi, McArthur, Mark, McDonnell, Olivia, McHugh, Maire, Moassefi, Mana, Morsi, Samah Mostafa, Muntenu, Alexander, Nandolia, Khanak K., Naqvi, Syed Raza, Nikanpour, Yalda, Alnoury, Mostafa, Nouh, Abdullah Mohamed Aly, Pappafava, Francesca, Patel, Markand D., Petrucci, Samantha, Rawie, Eric, Raymond, Scott, Roohani, Borna, Sabouhi, Sadeq, Sanchez-Garcia, Laura M., Shaked, Zoe, Suthar, Pokhraj P., Altes, Talissa, Isufi, Edvin, Dhermesh, Yaseen, Gass, Jaime, Thacker, Jonathan, Tarabishy, Abdul Rahman, Turner, Benjamin, Vacca, Sebastiano, Vilanilam, George K., Warren, Daniel, Weiss, David, Worede, Fikadu, Yousry, Sara, Lerebo, Wondwossen, Aristizabal, Alejandro, Karargyris, Alexandros, Kassem, Hasan, Pati, Sarthak, Sheller, Micah, Bakas, Spyridon, Rudie, Jeffrey D., and Aboian, Mariam

Subjects
Quantitative Biology - Other Quantitative Biology, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space.The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment.

Published
2023

3. Comparison of Volumetric and 2D-based Response Methods in the PNOC-001 Pediatric Low-Grade Glioma Clinical Trial

Author

von Reppert, Marc, primary, Ramakrishnan, Divya, additional, Brüningk, Sarah C, additional, Memon, Fatima, additional, Abi Fadel, Sandra, additional, Maleki, Nazanin, additional, Bahar, Ryan, additional, Avesta, Arman E, additional, Jekel, Leon, additional, Sala, Matthew, additional, Lost, Jan, additional, Tillmanns, Niklas, additional, Kaur, Manpreet, additional, Aneja, Sanjay, additional, Kazerooni, Anahita Fathi, additional, Nabavizadeh, Ali, additional, Lin, Ming De, additional, Hoffmann, Karl-Titus, additional, Bousabarah, Khaled, additional, Swanson, Kristin R, additional, Haas-Kogan, Daphne, additional, Mueller, Sabine, additional, and Aboian, Mariam S, additional

Published
2023
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4. Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas

Author

Tillmanns, Niklas, primary, Lost, Jan, additional, Tabor, Joanna, additional, Vasandani, Sagar, additional, Vetsa, Shaurey, additional, Marianayagam, Neelan, additional, Yalcin, Kanat, additional, Erson-Omay, E. Zeynep, additional, von Reppert, Marc, additional, Jekel, Leon, additional, Merkaj, Sara, additional, Ramakrishnan, Divya, additional, Avesta, Arman, additional, de Oliveira Santo, Irene Dixe, additional, Jin, Lan, additional, Huttner, Anita, additional, Bousabarah, Khaled, additional, Ikuta, Ichiro, additional, Lin, MingDe, additional, Aneja, Sanjay, additional, Turowski, Bernd, additional, Aboian, Mariam, additional, and Moliterno, Jennifer, additional

Published
2023
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6. Systematic Literature Review of Machine Learning Algorithms Using Pretherapy Radiologic Imaging for Glioma Molecular Subtype Prediction

Author

Lost, Jan, primary, Verma, Tej, additional, Jekel, Leon, additional, von Reppert, Marc, additional, Tillmanns, Niklas, additional, Merkaj, Sara, additional, Petersen, Gabriel Cassinelli, additional, Bahar, Ryan, additional, Gordem, Ayyüce, additional, Haider, Muhammad A., additional, Subramanian, Harry, additional, Brim, Waverly, additional, Ikuta, Ichiro, additional, Omuro, Antonio, additional, Conte, Gian Marco, additional, Marquez-Nostra, Bernadette V., additional, Avesta, Arman, additional, Bousabarah, Khaled, additional, Nabavizadeh, Ali, additional, Kazerooni, Anahita Fathi, additional, Aneja, Sanjay, additional, Bakas, Spyridon, additional, Lin, MingDe, additional, Sabel, Michael, additional, and Aboian, Mariam, additional

Published
2023
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7. NIMG-20. INCORPORATION OF AI-BASED AUTOSEGMENTATION AND CLASSIFICATION INTO NEURORADIOLOGY WORKFLOW: PACS-BASED AI TO BUILD YALE GLIOMA DATASET

Author

Lost, Jan, primary, Tillmans, Niklas, additional, Merkaj, Sara, additional, von Reppert, Marc, additional, Lin, MingDe, additional, Bousabarah, Khaled, additional, Huttner, Anita, additional, Aneja, Sanjay, additional, Omuro, Antonio, additional, Aboian, Mariam, additional, and Avesta, Arman, additional

Published
2022
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8. Identifying clinically applicable machine learning algorithms for glioma segmentation: recent advances and discoveries

Author

Tillmanns, Niklas, primary, Lum, Avery E, additional, Cassinelli, Gabriel, additional, Merkaj, Sara, additional, Verma, Tej, additional, Zeevi, Tal, additional, Staib, Lawrence, additional, Subramanian, Harry, additional, Bahar, Ryan C, additional, Brim, Waverly, additional, Lost, Jan, additional, Jekel, Leon, additional, Brackett, Alexandria, additional, Payabvash, Sam, additional, Ikuta, Ichiro, additional, Lin, MingDe, additional, Bousabarah, Khaled, additional, Johnson, Michele H, additional, Cui, Jin, additional, Malhotra, Ajay, additional, Omuro, Antonio, additional, Turowski, Bernd, additional, and Aboian, Mariam S, additional

Published
2022
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9. NIMG-46. SYSTEMATIC LITERATURE REVIEW OF ARTIFICIAL INTELLIGENCE ALGORITHMS USING PRE-THERAPY MR IMAGING FOR GLIOMA MOLECULAR SUBTYPE CLASSIFICATION

Author

Lost, Jan, primary, Verma, Tej, additional, Tillmanns, Niklas, additional, Brim, W R, additional, Subramanian, Harry, additional, Ikuta, Ichiro, additional, Bronen, Richard, additional, Zucconi, William, additional, Lin, Ming, additional, Bousabarah, Khaled, additional, Johnson, Michele, additional, Cui, Jin, additional, Malhotra, Ajay, additional, Sabel, Michael, additional, and Aboian, Mariam, additional

Published
2021
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10. The Brain Tumor Segmentation - Metastases (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI.

Author

Moawad AW, Janas A, Baid U, Ramakrishnan D, Saluja R, Ashraf N, Jekel L, Amiruddin R, Adewole M, Albrecht J, Anazodo U, Aneja S, Anwar SM, Bergquist T, Calabrese E, Chiang V, Chung V, Conte GMM, Dako F, Eddy J, Ezhov I, Familiar A, Farahani K, Iglesias JE, Jiang Z, Johanson E, Kazerooni AF, Kofler F, Krantchev K, LaBella D, Van Leemput K, Li HB, Linguraru MG, Link KE, Liu X, Maleki N, Meier Z, Menze BH, Moy H, Osenberg K, Piraud M, Reitman Z, Shinohara RT, Tahon NH, Nada A, Velichko YS, Wang C, Wiestler B, Wiggins W, Shafique U, Willms K, Avesta A, Bousabarah K, Chakrabarty S, Gennaro N, Holler W, Kaur M, LaMontagne P, Lin M, Lost J, Marcus DS, Maresca R, Merkaj S, Nada A, Pedersen GC, von Reppert M, Sotiras A, Teytelboym O, Tillmans N, Westerhoff M, Youssef A, Godfrey D, Floyd S, Rauschecker A, Villanueva-Meyer J, Pflüger I, Cho J, Bendszus M, Brugnara G, Cramer J, Perez-Carillo GJG, Johnson DR, Kam A, Kwan BYM, Lai L, Lall NU, Memon F, Patro SN, Petrovic B, So TY, Thompson G, Wu L, Schrickel EB, Bansal A, Barkhof F, Besada C, Chu S, Druzgal J, Dusoi A, Farage L, Feltrin F, Fong A, Fung SH, Gray RI, Ikuta I, Iv M, Postma AA, Mahajan A, Joyner D, Krumpelman C, Letourneau-Guillon L, Lincoln CM, Maros ME, Miller E, Morón F, Nimchinsky EA, Ozsarlak O, Patel U, Rohatgi S, Saha A, Sayah A, Schwartz ED, Shih R, Shiroishi MS, Small JE, Tanwar M, Valerie J, Weinberg BD, White ML, Young R, Zohrabian VM, Azizova A, Brüßeler MMT, Fehringer P, Ghonim M, Ghonim M, Gkampenis A, Okar A, Pasquini L, Sharifi Y, Singh G, Sollmann N, Soumala T, Taherzadeh M, Yordanov N, Vollmuth P, Foltyn-Dumitru M, Malhotra A, Abayazeed AH, Dellepiane F, Lohmann P, Pérez-García VM, Elhalawani H, Al-Rubaiey S, Armindo RD, Ashraf K, Asla MM, Badawy M, Bisschop J, Lomer NB, Bukatz J, Chen J, Cimflova P, Corr F, Crawley A, Deptula L, Elakhdar T, Shawali IH, Faghani S, Frick A, Gulati V, Haider MA, Hierro F, Dahl RH, Jacobs SM, Hsieh KJ, Kandemirli SG, Kersting K, Kida L, Kollia S, Koukoulithras I, Li X, Abouelatta A, Mansour A, Maria-Zamfirescu RC, Marsiglia M, Mateo-Camacho YS, McArthur M, McDonnell O, McHugh M, Moassefi M, Morsi SM, Muntenu A, Nandolia KK, Naqvi SR, Nikanpour Y, Alnoury M, Nouh AMA, Pappafava F, Patel MD, Petrucci S, Rawie E, Raymond S, Roohani B, Sabouhi S, Sanchez-Garcia LM, Shaked Z, Suthar PP, Altes T, Isufi E, Dhermesh Y, Gass J, Thacker J, Tarabishy AR, Turner B, Vacca S, Vilanilam GK, Warren D, Weiss D, Willms K, Worede F, Yousry S, Lerebo W, Aristizabal A, Karargyris A, Kassem H, Pati S, Sheller M, Bakas S, Rudie JD, and Aboian M

Abstract

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment., Competing Interests: Conflicts of Interest No conflicts of interest to disclose.

Published
2024

11. Systematic Literature Review of Machine Learning Algorithms Using Pretherapy Radiologic Imaging for Glioma Molecular Subtype Prediction.

Author

Lost J, Verma T, Jekel L, von Reppert M, Tillmanns N, Merkaj S, Petersen GC, Bahar R, Gordem A, Haider MA, Subramanian H, Brim W, Ikuta I, Omuro A, Conte GM, Marquez-Nostra BV, Avesta A, Bousabarah K, Nabavizadeh A, Kazerooni AF, Aneja S, Bakas S, Lin M, Sabel M, and Aboian M

Subjects
Humans, Machine Learning, Prognosis, Magnetic Resonance Imaging methods, Mutation, Glioma diagnostic imaging, Glioma genetics, Glioma therapy
Abstract

Background: The molecular profile of gliomas is a prognostic indicator for survival, driving clinical decision-making for treatment. Pathology-based molecular diagnosis is challenging because of the invasiveness of the procedure, exclusion from neoadjuvant therapy options, and the heterogeneous nature of the tumor., Purpose: We performed a systematic review of algorithms that predict molecular subtypes of gliomas from MR Imaging., Data Sources: Data sources were Ovid Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science., Study Selection: Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 12,318 abstracts were screened and 1323 underwent full-text review, with 85 articles meeting the inclusion criteria., Data Analysis: We compared prediction results from different machine learning approaches for predicting molecular subtypes of gliomas. Bias analysis was conducted for each study, following the Prediction model Risk Of Bias Assessment Tool (PROBAST) guidelines., Data Synthesis: Isocitrate dehydrogenase mutation status was reported with an area under the curve and accuracy of 0.88 and 85% in internal validation and 0.86 and 87% in limited external validation data sets, respectively. For the prediction of O6-methylguanine-DNA methyltransferase promoter methylation, the area under the curve and accuracy in internal validation data sets were 0.79 and 77%, and in limited external validation, 0.89 and 83%, respectively. PROBAST scoring demonstrated high bias in all articles., Limitations: The low number of external validation and studies with incomplete data resulted in unequal data analysis. Comparing the best prediction pipelines of each study may introduce bias., Conclusions: While the high area under the curve and accuracy for the prediction of molecular subtypes of gliomas are reported in internal and external validation data sets, limited use of external validation and the increased risk of bias in all articles may present obstacles for clinical translation of these techniques., (© 2023 by American Journal of Neuroradiology.)

Published
2023
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