title: Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model.
abstract: BACKGROUND
  The inability of structural MRI to accurately measure tumor response to therapy complicates care management for patients with gliomas. The purpose of this study was to assess the potential of several noninvasive functional and molecular MRI biomarkers for the assessment of glioma response to radiotherapy.
  
  
  METHODS
  Fourteen U87 tumor-bearing rats were irradiated using a small-animal radiation research platform (40 or 20 Gy), and 6 rats were used as controls. MRI was performed on a 4.7 T animal scanner, preradiation treatment, as well as at 3, 6, 9, and 14 days postradiation. Image features of the tumors, as well as tumor volumes and animal survival, were quantitatively compared.
  
  
  RESULTS
  Structural MRI showed that all irradiated tumors still grew in size during the initial days postradiation. The apparent diffusion coefficient (ADC) values of tumors increased significantly postradiation (40 and 20 Gy), except at day 3 postradiation, compared with preradiation. The tumor blood flow decreased significantly postradiation (40 and 20 Gy), but the relative blood flow (tumor vs contralateral) did not show a significant change at most time points postradiation. The amide proton transfer weighted (APTw) signals of the tumor decreased significantly at all time points postradiation (40 Gy), and also at day 9 postradiation (20 Gy). The blood flow and APTw maps demonstrated tumor features that were similar to those seen on gadolinium-enhanced T1-weighted images.
  
  
  CONCLUSIONS
  Tumor ADC, blood flow, and APTw were all useful imaging biomarkers by which to predict glioma response to radiotherapy. The APTw signal was most promising for early response assessment in this model.
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hong
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Meiyun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Kai
authors.initials: K
authors.lastname: Ding
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Bachchu
authors.initials: B
authors.lastname: Lal
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Betty
authors.initials: B
authors.lastname: Tyler
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Antonella
authors.initials: A
authors.lastname: Mangraviti
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Silun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: John
authors.initials: J
authors.lastname: Laterra
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland (X.H., M.W., Y.F., B.M., S.W., J.Z.); Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (X.H., L.L.); Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (K.D., J.W.); Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland (B.L., J.L.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (B.T., A.M.); Department of Neurology, Johns Hopkins University, Baltimore, Maryland (J.L.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (J.Z.).
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015415:Biomarkers; D001932:Brain Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D004195:Disease Models, Animal; D005910:Glioma / Q000473:pathology* / Q000532:radiotherapy*; D007091:Image Processing, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011522:Protons; D051381:Rats; D011923:Rats, Nude
chemical_list: D015415:Biomarkers; D011522:Protons
keywords: APT imaging; glioma; multiparametric MRI; radiotherapy; response assessment