Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma
Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma
This research is being done to study the pattern of changes in various parts of the magnetic
 resonance imaging (MRI) studies that patients have done to help plan their radiation therapy
 and to evaluate the effects of therapy.

 The MRI of the brain is one of the major ways a participant's doctors determine how to treat
 a participant's tumor and if the participant's tumor is growing or not. In this study the
 investigators want to learn if new sequences added to the MRI that the investigators are
 already getting to guide partipants' radiation treatment can be analyzed to help make better
 treatment decisions. MRI sequences that examine the composition and structure of the tissues
 in the brain in a different way will be obtained. These are called called Amide Proton
 Transfer (APT) and Diffusion Weighted MRI.

 These scans will first be performed at the time of participants' radiation plannings scan
 done before treatment and near the end of the course of radiation treatments. This will allow
 the study team to investigate if there are changes in these sequences before radiation
 treatment and to see if using these MRI studies will allow us to better plan radiation
 treatments for patients in the future. This pre-treatment scan will be done at the same time
 as participants' standard radiation planning MRI, but will cause the scan to take longer.
 Participants will also have an extra MRI during one of the last 5 days of the planned 28-33
 radiation treatments that are standardly used. This additional scan will not include
 administration of injected contrast agents, and would occur on a day when participants are
 also coming in for radiation. This scan will be compared with the first scan. The
 investigators will determine whether these changes may predict later long term outcome of
 treatment for patients. Patients who enroll in this study will get all of the standard
 therapy they would get for their tumor whether or not they participate in this study. There
 is no extra or different therapy given.

 The investigators anticipate that the radiation treatment volumes created using APT will
 largely overlap with the conventional plan but will be distinct at the margins. Disease
 failure is more likely to occur in areas with APT abnormalities suggestive of active tumor.
 In patients that have failure outside the contrast enhancing area, the region of failure will
 be predicted by regions of increased APT activity. Current MRI sequences do not allow for
 prediction of regions of recurrence or progression, or distinguish between tumor, pressure,
 or surgical injury as the cause of FLAIR/T2 abnormalities. Disease failure is more likely to
 occur in areas with APT abnormalities suggestive of active tumor. In patients that have
 failure outside the contrast enhancing area, the region of failure will be predicted by
 regions of increased APT activity. Current MRI sequences do not allow for prediction of
 regions of recurrence or progression, or distinguish between tumor, pressure, or surgical
 injury as the cause of FLAIR/T2 abnormalities. Volume containing elevated APT signal may be
 associated with outcome (survival). In an exploratory analysis, the investigators will
 evaluate whether there are characteristic patterns that should be prospectively studied in a
 larger trial.
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.
Inclusion Criteria:

 1. Pathologically Confirmed Glioma after completion of planned biopsy or resection.

 High grade glioma histologies:

 -  Glioblastoma

 -  High Grade or Malignant Glioma

 -  Anaplastic Astrocytoma

 -  Anaplastic Oligodendroglioma

 -  Gliosarcoma

 -  Mixture of any of the above histologies Low Grade Histologies

 -  Astrocytoma

 -  Grade II or low grade glioma

 -  Oligodendroglioma

 -  Mixtures of the above histologies

 2. Plan to undergo external radiation treatment as part of therapy

 3. No prior therapeutic cranial radiotherapy

 4. Can safely perform clinically indicated MRI (no contraindications to MRI with
 Gadolinium) as determined by the standard Johns Hopkins Radiation Oncology screening
 procedures,

 Exclusion Criteria:

 1. Patients who cannot undergo MRIs.

 2. Patients who are allergic to gadolinium based contrast agent

 3. Patients who have cardiac pacemaker or other electronic or metal implant

 4. Patients who have chronic kidney disease judged sufficient to exclude them from the
 clinically indicated contrast enhanced MRI.

 5. Female patients who is pregnant