The overall goal of this academic-industrial partnership between researchers at Johns Hopkins University and Philips Healthcare/Philips Research is to develop and optimize the novel amide proton transfer (APT) imaging technique for efficient and reliable detection of malignant brain tumors and assessment of treatment response. APT imaging can provide endogenous contrast related to mobile protein content in tissue. Preclinical studies and clinical data suggest that APT imaging may provide unique information about the presence and grade of brain tumors, as revealed by MRI-guided proteomics and in vivo MR spectroscopy. Notably, we recently demonstrated in animal models that the APT-MRI signal is a unique imaging biomarker to distinguish between radiation necrosis and active tumor tissue. Similar to other MRI techniques, the ultimate goal for APT imaging is the standardized use in a clinical setting. However, current APT imaging protocols are far from being optimized. A main reason is that the APT experimental parameters are often limited by scanner hardware constraints, particularly with respect to amplifier duty-cycle and specific absorption rate requirements. In addition to pulse sequence parameter differences, leading to inconsistent effect sizes, data processing strategies vary and may affect the reproducibility of results between hospitals. Therefore, there is an urgent need for industry and academia to work together to develop this emerging technology into a clinically viable, easy-to-use, and reproducible approach. To accomplish this, we (researchers at JHU and Philips) agreed to establish a cooperation to achieve an accelerated APT translation. Together, we formulated the following two specific aims: (1) Optimize and standardize APT imaging technology on 3T human MRI systems; and (2) Test the methodologies developed in Aim 1 on patients with brain tumors. APT imaging has the potential to introduce an entirely new molecular MRI methodology into the clinic that can detect endogenous cellular protein signals in biological tissue non-invasively. Thi research will provide the standard optimized approaches required to translate this new technology into the clinic.

Public Health Relevance

The overall goal of this academic-industrial partnership is to optimize a novel MR molecular imaging technique, called amide proton transfer imaging, for efficient and reliable detection of malignant brain tumors on 3T human MRI scanners. If successful, we expect to provide an entirely new and optimized whole-brain imaging technology that can reliably identify the spatial extent of high grade tumors non-invasively, for both contras-enhancing and non-enhancing gliomas. This specific MRI modality is expected to aid in the diagnosis and treatment of brain tumors, directly impacting patient care.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
4R01CA166171-04
Application #
8997457
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Zhang, Huiming
Project Start
2013-02-05
Project End
2018-01-31
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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
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
Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo et al. (2017) Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. Eur Radiol 27:3181-3189
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

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