Malignant brain tumors remain one of the deadliest forms of cancer despite maximal surgical intervention, radiation therapy and chemotherapy. Limitations in neuroimaging technology complicate the clinical management of patients with gliomas and impede efficient testing of new therapeutics. Recently, we have designed a new magnetization transfer-based MRI technique, dubbed amide proton transfer (APT) imaging, that detects a variety of amide protons of endogenous mobile proteins and peptides, such as those in the cytoplasm. Our preclinical studies and pilot clinical data using single-slice acquisition suggest that APT may provide unique information about the presence and grade of brain tumors based on increased cellular content of proteins and peptides, as revealed by MRI-guided proteomics and in vivo MR spectroscopy. However, many technical problems have to be resolved before this technique can be applied reliably for whole-brain imaging in a clinical setting. The overall goals of this proposal are to develop a fast whole-brain APT methodology for use in the clinic and to assess the capability for APT to provide unique visual data about heterogeneous portions of gliomas when compared to standard MRI sequences. To achieve this goal, we have assembled a multidisciplinary team of basic scientists and clinicians, within the framework of a national brain cancer program, who will each contribute their particular expertise in the fields of physics, biostatistics, oncology, neurosurgery, pathology, and neuroradiology.
Our specific aims are: (1) Develop a time-efficient whole-brain APT imaging technique at 3T for clinical application, (2) Determine the sensitivity and specificity of APT imaging at 3T in evaluating heterogeneous brain tumors by distinguishing tumor core from peritumoral edema and low- from high-grade gliomas, (3) Explore the origin of the APT contrast for brain tumors using APT-image guided biopsy to allow histologic validation, and (4) explore the feasibility and optimal quality of APT imaging at 7T. This work has the potential to yield a clinically applicable new MRI technique that is unique in its ability to image tissue at the protein and peptide level. This may improve the diagnostic accuracy of brain MRI for malignant gliomas and, potentially, other diseases of the brain and, hence, is of enormous clinical importance.

Public Health Relevance

The goal of this project is to develop a novel protein and peptide-based MRI technique, called amide proton transfer (APT) imaging, and to determine the sensitivity and specificity of APT imaging for the detection of brain tumors. APT-MRI may improve the diagnostic and surgical accuracy in treating malignant gliomas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009731-04
Application #
8245046
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Liu, Guoying
Project Start
2009-07-01
Project End
2013-09-22
Budget Start
2012-05-01
Budget End
2013-09-22
Support Year
4
Fiscal Year
2012
Total Cost
$350,383
Indirect Cost
$120,996
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Joo, Bio; Han, Kyunghwa; Choi, Yoon Seong et al. (2018) Amide proton transfer imaging for differentiation of benign and atypical meningiomas. Eur Radiol 28:331-339
Sun, Hongzan; Xin, Jun; Zhou, Jinyuan et al. (2018) 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 20:473-481
Jiang, Shanshan; Rui, Qihong; Wang, Yu et al. (2018) Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics. Eur Radiol 28:2115-2123
Jiang, Shanshan; Eberhart, Charles G; Lim, Michael et al. (2018) Identifying Recurrent Malignant Glioma after Treatment Using Amide Proton Transfer-Weighted MR Imaging: A Validation Study with Image-Guided Stereotactic Biopsy. Clin Cancer Res :
Zou, Tianyu; Yu, Hao; Jiang, Chunxiu et al. (2018) Differentiating the histologic grades of gliomas preoperatively using amide proton transfer-weighted (APTW) and intravoxel incoherent motion MRI. NMR Biomed 31:
Zhang, Yi; Liu, Xiaoyang; Zhou, Jinyuan et al. (2018) Ultrafast compartmentalized relaxation time mapping with linear algebraic modeling. Magn Reson Med 79:286-297
Li, Chunmei; Chen, Min; Zhao, Xuna et al. (2017) Chemical Exchange Saturation Transfer MRI Signal Loss of the Substantia Nigra as an Imaging Biomarker to Evaluate the Diagnosis and Severity of Parkinson's Disease. Front Neurosci 11:489
Heo, Hye-Young; Zhang, Yi; Burton, Tina M et al. (2017) Improving the detection sensitivity of pH-weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals. Magn Reson Med 78:871-880
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

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