Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma

Currently, all brain tumors are routinely evaluated using gadolinium contrast-enhanced (Gd-CE) MRI, in combination with T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI, which are used to determine the extent of tumor involvement to guide treatments, and to assess therapeutic response. However, Gd-CE only depicts disruption of the blood brain barrier and is not specific for tumor activity. Therefore, standard MRI may not be optimal in defining the true extent of tumor, defining as abnormal areas that may contain only edema related to mass effect or surgery and miss tumor extensions that do not sufficiently disrupt the blood-brain-barrier. In addition, in the setting of radiation therapy which also disrupts the blood brain barrier, it does not serve as an early marker of tumor response. The primary goal of the current observational study is to explore whether Amide Proton Transfer (APT) imaging can better determine the extent of tumor involvement. APT signal is created by mobile cytoplasmic proteins, which are increased in malignant brain tumors and have been found in preclinical and clinical studies to be associated with a high APT weighted signal in glioma. Such imaging may provide information that may improve the ability of MR imaging to guide targeting of radiotherapy. In particular, it may (1) detect tumor bearing brain that is not contrast enhancing on the standard brain MRI scan for patients with high grade glioma and/or (2) fail to confirm tumor in areas of brain identified as abnormal on standard MRI. The investigators will also explore patterns of disease failure in patients with malignant gliomas to validate the observations, and whether such imaging may predict outcome. Similar questions may be important in the therapy of low grade glioma, and an exploratory informational cohort of patients with this less common diagnosis will be accrued during the study period to inform decisions about whether further study is desirable. A second APT image will be obtained during the final week of treatment for enrolled patients to determine whether changes in APT signal occur, and whether there is evidence that this may be prognostic for treatment success or failure when correlated with progression free survival and survival outcome. Currently, there is no imaging method to assess tumor response and predict outcome within the first several months as a result of the confounding effect of radiation on both the tumor and surrounding brain. In addition, standard brief apparent diffusion coefficient (ADC) MRI sequences will be performed as part of the pretreatment imaging and the end of treatment scan as an additional potential early imaging biomarker that may be a part of multiparametric assessment of response to radiotherapy as identified in preclinical studies performed at Johns Hopkins. These first steps may form the basis for possible future studies to assess new approaches to radiation planning for patients with brain cancer.