Despite recent advances in surgery, radiation, and chemotherapy, malignant gliomas remain universally fatal, with a median survival of 12-15 months for glioblastoma and 2-5 years for anaplastic astrocytoma. Limitations in neuroimaging complicate the clinical management of patients with gliomas, and impede efficient testing of new therapeutics. Amide proton transfer (APT) imaging is a novel molecular MRI technique that generates image contrast based on the endogenous cellular proteins in tissue. This APT imaging project has been extremely successful during the first grant period (7/09-4/13). We developed several relatively fast three- dimensional APT imaging sequences at 3T and 7T and established several effective image acquisition protocols and image processing approaches for imaging of human brain tumors. In addition, we demonstrated that APT imaging is a highly valuable addition to the MRI armamentarium for the more specific characterization of human brain tumors. Notably, our preclinical study in various glioma models and models of radiation- induced necrosis in rats clearly showed that active glioma (hyperintense) and radiation necrosis (hypointense or isointense) exhibited opposite APT-MRI signals, and could thus readily be distinguished. These preclinical results are exciting, and, if validated with appropriately powered studies in patients, the implications for clinical care and experimental therapeutics will be enormous. The ultimate goal for APT imaging is its standard use in a clinical setting on a variety of MRI systems from different vendors. However, clinical APT-MRI experiments are often limited by scanner hardware constraints (particularly amplifier duty cycle and pulse length) and specific absorption rate (SAR) requirements. Therefore, current APT imaging protocols vary substantially among different institutes, far from being optimized, and the results acquired from different research centers are difficult to compare to one another. The overall goals of this renewal application are to refine this important protein-based molecular MRI technology into a sensitive, user-friendly, and clinically reproducible approach and to demonstrate its potential to help resolve several diagnostic dilemmas in brain cancer therapy. Based on the results obtained in the previous grant period and recent progress in the field, we have designed the following three specific aims: (1) implement and optimize the parallel RF transmission (pTX)-based APT-MRI technique at 3T;(2) evaluate the clinical value of APT-MRI in identifying non-Gd-enhancing high-grade gliomas;and (3) quantify the accuracy of APT-MRI in distinguishing pseudoprogression from true tumor progression in GBM treated with chemoradiation therapy. If this step of the APT investigation is successful, this research will provide the optimized approaches and critical sensitivity and specificity data required to translate this important APT-MRI technology into the clinic.

Public Health Relevance

This renewal project aims to refine the novel protein-based amide proton transfer (APT) imaging technology into a sensitive and highly reproducible approach and to evaluate the ultimate potential of this important MRI technique for the noninvasive molecular diagnosis of malignant brain tumors before and after treatment. The evaluation will address some major diagnostic dilemmas in the management of patients with brain cancer. If successful, the research will significantly improve the accuracy of tissue sampling and response assessment for patients with malignant brain tumors, directly and rapidly impacting patient care.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Special Emphasis Panel (ZRG1-DTCS-A (81))
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Liu, Guoying
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Johns Hopkins University
Schools of Medicine
United States
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Lu, Jianhua; Zhou, Jinyuan; Cai, Congbo et al. (2015) Observation of true and pseudo NOE signals using CEST-MRI and CEST-MRS sequences with and without lipid suppression. Magn Reson Med 73:1615-22
Zhang, Yi; Zhou, Jinyuan; Bottomley, Paul A (2015) Minimizing lipid signal bleed in brain (1) H chemical shift imaging by post-acquisition grid shifting. Magn Reson Med 74:320-9
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
Li, Chunmei; Peng, Shuai; Wang, Rui et al. (2014) Chemical exchange saturation transfer MR imaging of Parkinson's disease at 3 Tesla. Eur Radiol 24:2631-9
Lu, Jianhua; Cai, Congbo; Cai, Shuhui et al. (2014) Chemical exchange saturation transfer MRI using intermolecular double-quantum coherences with multiple refocusing pulses. Magn Reson Imaging 32:759-65
Yuan, Jing; Chen, Shuzhong; King, Ann D et al. (2014) Amide proton transfer-weighted imaging of the head and neck at 3?T: a feasibility study on healthy human subjects and patients with head and neck cancer. NMR Biomed 27:1239-47
Xu, Jiadi; Yadav, Nirbhay N; Bar-Shir, Amnon et al. (2014) Variable delay multi-pulse train for fast chemical exchange saturation transfer and relayed-nuclear overhauser enhancement MRI. Magn Reson Med 71:1798-812
Wei, Wenbo; Jia, Guang; Flanigan, David et al. (2014) Chemical exchange saturation transfer MR imaging of articular cartilage glycosaminoglycans at 3 T: Accuracy of B0 Field Inhomogeneity corrections with gradient echo method. Magn Reson Imaging 32:41-7
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
Zhang, Yi; Gabr, Refaat E; Zhou, Jinyuan et al. (2013) Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding. J Magn Reson 237:125-38

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