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
Jiang, Shanshan; Yu, Hao; Wang, Xianlong et al. (2016) Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla. Eur Radiol 26:64-71
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2016) Selecting the reference image for registration of CEST series. J Magn Reson Imaging 43:756-61
Heo, Hye-Young; Lee, Dong-Hoon; Zhang, Yi et al. (2016) Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging. Magn Reson Med :
Ma, Bo; Blakeley, Jaishri O; Hong, Xiaohua et al. (2016) Applying amide proton transfer-weighted MRI to distinguish pseudoprogression from true progression in malignant gliomas. J Magn Reson Imaging 44:456-62
Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Kai et al. (2016) 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 :
Heo, Hye-Young; Zhang, Yi; Jiang, Shanshan et al. (2016) Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semisolid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at Magn Reson Med 75:1630-9
Yu, Yang; Lee, Dong-Hoon; Peng, Shin-Lei et al. (2016) Assessment of Glioma Response to Radiotherapy Using Multiple MRI Biomarkers with Manual and Semiautomated Segmentation Algorithms. J Neuroimaging 26:626-634
Deng, Min; Chen, Shu-Zhong; Yuan, Jing et al. (2016) Chemical Exchange Saturation Transfer (CEST) MR Technique for Liver Imaging at 3.0 Tesla: an Evaluation of Different Offset Number and an After-Meal and Over-Night-Fast Comparison. Mol Imaging Biol 18:274-82
Heo, Hye-Young; Zhang, Yi; Lee, Dong-Hoon et al. (2016) Accelerating chemical exchange saturation transfer (CEST) MRI by combining compressed sensing and sensitivity encoding techniques. Magn Reson Med :
Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon et al. (2016) Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE). Magn Reson Med :

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