The overall goal of this application is to develop novel protein-based MRI approaches and to demonstrate their potential to resolve the diagnostic dilemma of treatment effects in neuro-oncology. Radiation therapy is a key modality for the treatment of malignant brain tumors, and radiation necrosis is a major complication of radiation therapy. The inability of currently available MRI techniques to differentiate tumor progression from radiation necrosis after brain tumor therapy complicates daily patient care, and is a critical barrier to investigating the efficacy of new therapies for brain tumors. Recently, we have designed a new molecular MRI technique, dubbed amide proton transfer (APT) imaging, which detects amide protons of endogenous mobile proteins and peptides in tissue. Our preliminary data in preclinical models demonstrate that APT imaging provides a unique signal in untreated glioma (hyperintense relative to normal and normal-appearing contralateral tissue), compared to pure radiation necrosis (hypointense or isointense).
The specific aims of this proposal are: (i) Optimize our protein-based MRI techniques and determine their accuracy in distinguishing radiation necrosis from tumor recurrence and (ii) Evaluate whether APT-MRI signal is an early biomarker to predict tumor response and animal survival. To achieve our goal, we have assembled a multidisciplinary team of basic scientists and clinicians. The results of this preclinical study will provide the first accuracy data for a new imaging biomarker for identifying tumor progression versus radiation necrosis, and for the prediction the efficacy of radiation therapy in malignant gliomas. These data are needed for a further study in clinical populations.
Our goal is to evaluate the ability and accuracy to distinguish between radiation necrosis and active tumor in preclinical models using a novel protein-based molecular MRI approach. The results would establish a new non-invasive MRI biomarker for assessing viable malignancy versus radiation necrosis and predicting tumor response to therapy.
|Hong, Xiaohua; Liu, Li; Wang, Meiyun et al. (2014) Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model. Neuro Oncol 16:856-67|
|Zhou, Jinyuan; Zhu, He; Lim, Michael et al. (2013) Three-dimensional amide proton transfer MR imaging of gliomas: Initial experience and comparison with gadolinium enhancement. J Magn Reson Imaging 38:1119-28|
|Zhou, Jinyuan; Hong, Xiaohua; Zhao, Xuna et al. (2013) APT-weighted and NOE-weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses. Magn Reson Med 70:320-7|
|Zhao, Xuna; Wen, Zhibo; Zhang, Ge et al. (2013) Three-dimensional turbo-spin-echo amide proton transfer MR imaging at 3-Tesla and its application to high-grade human brain tumors. Mol Imaging Biol 15:114-22|