Research ArticleORIGINAL RESEARCH
Imaging Clusters of Pediatric Low-Grade Glioma are Associated with Distinct Molecular Characteristics
Anahita Fathi Kazerooni, Adam Kraya, Komal S. Rathi, Meen Chul Kim, Varun Kesherwani, Ryan Corbett, Arastoo Vossough, Nastaran Khalili, Deep Gandhi, Neda Khalili Ariana M. Familiar, Run Jin, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R. Lueder, Saksham Phul, Phillip B. Storm, Jeffrey B. Ware, Jessica B. Foster, Sabine Mueller, Jo Lynne Rokita, Michael J. Fisher, Adam C. Resnick and Ali Nabavizadeh
American Journal of Neuroradiology February 2025, ajnr.A8699; DOI: https://doi.org/10.3174/ajnr.A8699
Anahita Fathi Kazerooni
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Adam Kraya
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Komal S. Rathi
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Meen Chul Kim
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Varun Kesherwani
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Ryan Corbett
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Arastoo Vossough
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Nastaran Khalili
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Deep Gandhi
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Neda Khalili Ariana M. Familiar
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Run Jin
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Xiaoyan Huang
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Yuankun Zhu
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Alex Sickler
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Matthew R. Lueder
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Saksham Phul
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Phillip B. Storm
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Jeffrey B. Ware
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Jessica B. Foster
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Sabine Mueller
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Jo Lynne Rokita
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Michael J. Fisher
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Adam C. Resnick
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
Ali Nabavizadeh
From the Division of Neurosurgery (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S., M.R.L., S.P., P.B.S., A.C.R.,A.N.), Centre for Data-Driven Discovery in Biomedicine (D3b) (A.F.K., A.K., K.R., M.C.K., V.K., N.K., A.M.F., R.J., N.K., D.G., X.H., Y.Z., A.S.,M.R.L., S.P., P.B.S., A.C.R., A.N.), Department of Radiology (A.V.), Department of Pathology and Laboratory Medicine (M.R.L.), Division of Oncology (J.B.F., M.J.F.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Neurosurgery (A.F.K., P.B.S., A.C.R.), Department of Radiology (A.N., J.B.W.), Department of Pediatrics (J.B.F.), University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pediatrics (R.C., J.L.R.), The George Washington University, Washington, DC, USA; Department of Neurology and Pediatrics (S.M.), University of California San Francisco, San Francisco, CA, USA.
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ABSTRACT
BACKGROUND AND PURPOSE: Cancers show heterogeneity at various levels, from genome to radiological imaging. This study aimed to explore the interplay between genomic, transcriptomic, and radiophenotypic data in pediatric low-grade glioma (pLGG), the most common group of brain tumors in children.
MATERIALS AND METHODS: We analyzed data from 201 pLGG patients in the Children’s Brain Tumor Network (CBTN), using principal component analysis and K-Means clustering on 881 radiomic features, along with clinical variables (age, sex, tumor location), to identify imaging clusters and examine their association with 2021 WHO pLGG classifications. To determine the transcriptome pathways linked to imaging clusters, we employed a supervised machine learning model with elastic net logistic regression based on the pathways identified through gene set enrichment and gene co-expression network analyses.
RESULTS: Three imaging clusters with distinct radiomic characteristics were identified. BRAF V600E mutations were primarily found in imaging cluster 3, while KIAA1549::BRAF fusion occurred in subtype 1. The model's predictive accuracy (AUC) was 0.77 for subtype 1, 0.78 for subtype 2, and 0.70 for subtype 3. Each imaging cluster exhibited unique molecular mechanisms: subtype 1 was linked to oxidative phosphorylation, PDGFRB, and interleukin signaling, whereas subtype 3 was associated with histone acetylation and DNA methylation pathways, related to BRAF V600E pLGGs.
CONCLUSIONS: Our radiogenomics study indicates that the intrinsic molecular characteristics of tumors correlate with distinct imaging subgroups in pLGG, paving the way for future multi-modal investigations that may enhance understanding of disease progression and targetability.
ABBREVIATIONS: WHO = World Health Organization; CBTN = Children’s Brain Tumor Network; pLGG = pediatric Low-Grade Glioma; EFS = Event-Free Survival; PC = Principal Component; CNS = Central Nervous System.
Footnotes
The authors declare no conflicts of interest related to the content of this article.
- © 2025 by American Journal of Neuroradiology
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Accepted Manuscript
Anahita Fathi Kazerooni, Adam Kraya, Komal S. Rathi, Meen Chul Kim, Varun Kesherwani, Ryan Corbett, Arastoo Vossough, Nastaran Khalili, Deep Gandhi, Neda Khalili Ariana M. Familiar, Run Jin, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R. Lueder, Saksham Phul, Phillip B. Storm, Jeffrey B. Ware, Jessica B. Foster, Sabine Mueller, Jo Lynne Rokita, Michael J. Fisher, Adam C. Resnick, Ali Nabavizadeh
Imaging Clusters of Pediatric Low-Grade Glioma are Associated with Distinct Molecular Characteristics
American Journal of Neuroradiology Feb 2025, ajnr.A8699; DOI: 10.3174/ajnr.A8699
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Accepted Manuscript
Imaging Clusters of Pediatric Low-Grade Glioma are Associated with Distinct Molecular Characteristics
Anahita Fathi Kazerooni, Adam Kraya, Komal S. Rathi, Meen Chul Kim, Varun Kesherwani, Ryan Corbett, Arastoo Vossough, Nastaran Khalili, Deep Gandhi, Neda Khalili Ariana M. Familiar, Run Jin, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R. Lueder, Saksham Phul, Phillip B. Storm, Jeffrey B. Ware, Jessica B. Foster, Sabine Mueller, Jo Lynne Rokita, Michael J. Fisher, Adam C. Resnick, Ali Nabavizadeh
American Journal of Neuroradiology Feb 2025, ajnr.A8699; DOI: 10.3174/ajnr.A8699
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