title: Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.
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.
authors.affiliation: 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.).
authors.forename: Luke
authors.initials: L
authors.lastname: Macyszyn
authors.affiliation: 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.).
authors.forename: Hamed
authors.initials: H
authors.lastname: Akbari
authors.affiliation: 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.).
authors.forename: Jared M
authors.initials: JM
authors.lastname: Pisapia
authors.affiliation: 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.).
authors.forename: Xiao
authors.initials: X
authors.lastname: Da
authors.affiliation: 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.).
authors.forename: Mark
authors.initials: M
authors.lastname: Attiah
authors.affiliation: 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.).
authors.forename: Vadim
authors.initials: V
authors.lastname: Pigrish
authors.affiliation: 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.).
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Bi
authors.affiliation: 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.).
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Pal
authors.affiliation: 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.).
authors.forename: Ramana V
authors.initials: RV
authors.lastname: Davuluri
authors.affiliation: 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.).
authors.forename: Laura
authors.initials: L
authors.lastname: Roccograndi
authors.affiliation: 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.).
authors.forename: Nadia
authors.initials: N
authors.lastname: Dahmane
authors.affiliation: 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.).
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez-Lage
authors.affiliation: 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.).
authors.forename: George
authors.initials: G
authors.lastname: Biros
authors.affiliation: 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.).
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolf
authors.affiliation: 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.).
authors.forename: Michel
authors.initials: M
authors.lastname: Bilello
authors.affiliation: 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.).
authors.forename: Donald M
authors.initials: DM
authors.lastname: O'Rourke
authors.affiliation: 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.).
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
mesh_terms: D000328:Adult; D000465:Algorithms; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D000069550:Machine Learning; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged
keywords: glioblastoma; imaging; machine learning; predict; survival