title: Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas.
abstract: High-grade gliomas with mutations in the isocitrate dehydrogenase (IDH) gene family confer longer overall survival relative to their IDH-wild-type counterparts. Accurate determination of the IDH genotype preoperatively may have both prognostic and diagnostic value. The current study used a machine-learning algorithm to generate a model predictive of IDH genotype in high-grade gliomas based on clinical variables and multimodal features extracted from conventional MRI.
  
  
  
  Preoperative MRIs were obtained for 120 patients with primary grades III (n = 35) and IV (n = 85) glioma in this retrospective study. IDH genotype was confirmed for grade III (32/35, 91%) and IV (22/85, 26%) tumors by immunohistochemistry, spectrometry-based mutation genotyping (OncoMap), or multiplex exome sequencing (OncoPanel). IDH1 and IDH2 mutations were mutually exclusive, and all mutated tumors were collapsed into one IDH-mutated cohort. Cases were randomly assigned to either the training (n = 90) or validation cohort (n = 30). A total of 2970 imaging features were extracted from pre- and postcontrast T1-weighted, T2-weighted, and apparent diffusion coefficient map. Using a random forest algorithm, nonredundant features were integrated with clinical data to generate a model predictive of IDH genotype.
  
  
  
  Our model achieved accuracies of 86% (area under the curve [AUC] = 0.8830) in the training cohort and 89% (AUC = 0.9231) in the validation cohort. Features with the highest predictive value included patient age as well as parametric intensity, texture, and shape features.
  
  
  
  Using a machine-learning algorithm, we achieved accurate prediction of IDH genotype in high-grade gliomas with preoperative clinical and MRI features.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Biqi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Ken
authors.initials: K
authors.lastname: Chang
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Shyam
authors.initials: S
authors.lastname: Tanguturi
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Wenya Linda
authors.initials: WL
authors.lastname: Bi
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Brian M
authors.initials: BM
authors.lastname: Alexander
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.).
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (B.Z., K.C., R.Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Harvard Medical School, Boston, Massachusetts (S.R., K.L.L.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (S.R., K.L.L.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts(S.R., D.A.R., K.L.L., P.Y.W.); Harvard Radiation Oncology Program, Boston, Massachusetts (S.T.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (B.M.A.) ryhuang@partners.org.
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019540:Area Under Curve; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: MRI; high-grade glioma; isocitrate dehydrogenase; machine learning; prediction