Luke Macyszyn1, Hamed Akbari1, Jared M Pisapia1, Xiao Da1, Mark Attiah1, Vadim Pigrish1, Yingtao Bi1, Sharmistha Pal1, Ramana V Davuluri1, Laura Roccograndi1, Nadia Dahmane1, Maria Martinez-Lage1, George Biros1, Ronald L Wolf1, Michel Bilello1, Donald M O'Rourke1, Christos Davatzikos1. 1. Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania (L.M., J.M.P., M.A., L.R., N.D., D.M.O.); Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania (H.A., X.D., R.L.W., M.B., C.D.); Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania (H.A., X.D., V.P., M.B., C.D.); Department of Biomedical Informatics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Y.B., S.P., R.V.D.); Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas (G.B.); Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (M.M.-L., D.M.O.).
Abstract
BACKGROUND: MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). METHODS: One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. RESULTS: Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. CONCLUSIONS: By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients.
BACKGROUND: MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). METHODS: One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. RESULTS: Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. CONCLUSIONS: By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients.
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