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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009731-06
Application #
8737897
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Liu, Guoying
Project Start
2009-07-01
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Jiang, Shanshan; Rui, Qihong; Wang, Yu et al. (2017) Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics. Eur Radiol :
Wang, Wenzhu; Zhang, Hong; Lee, Doon-Hoon et al. (2017) Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury. Brain Behav Immun 64:344-353
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2017) Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE). Magn Reson Med 77:2225-2238
Jeong, Ha-Kyu; Han, Kyunghwa; Zhou, Jinyuan et al. (2017) Characterizing amide proton transfer imaging in haemorrhage brain lesions using 3T MRI. Eur Radiol 27:1577-1584
Heo, Hye-Young; Zhang, Yi; Lee, Dong-Hoon et al. (2017) Accelerating chemical exchange saturation transfer (CEST) MRI by combining compressed sensing and sensitivity encoding techniques. Magn Reson Med 77:779-786
Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Kai et al. (2017) Quantitative assessment of the effects of water proton concentration and water T1 changes on amide proton transfer (APT) and nuclear overhauser enhancement (NOE) MRI: The origin of the APT imaging signal in brain tumor. Magn Reson Med 77:855-863
Yu, Hao; Lou, Huiling; Zou, Tianyu et al. (2017) Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma. Eur Radiol 27:4516-4524
Yang, Jie; Li, Qian; Wang, Zhongyu et al. (2017) Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice. Sci Rep 7:40358
Zhang, Yi; Heo, Hye-Young; Jiang, Shanshan et al. (2017) Fast, Reliable 3D Amide Proton Transfer Imaging of Brain Tumors at 3T with Variably-accelerated Sensitivity Encoding (vSENSE). Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson M 25:
Sun, Hongzan; Xin, Jun; Zhou, Jinyuan et al. (2017) Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [18F]FDG PET. Mol Imaging Biol :

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