MR Imaging of Mobile Proteins for Human Brain Tumor Detection

Jinyuan Zhou, Ph.D.

Johns Hopkins University

Funded in June, 2007: $100000 for 3 years
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LAY SUMMARY

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A New MRI Technique May Aid Brain Tumor Diagnosis and Surgery

Researchers will test the ability of a new MRI imaging technique to assess the grade (stage) of brain tumor and to distinguish solid tumor from surrounding edema.   

Although MRI imaging is the standard of care for assessing deadly brain tumors called gliomas before surgery and for guiding surgical removal of the tumor, MRI has limited potential for “grading” the severity of the tumor or distinguishing tumor from surrounding edema.  The Johns Hopkins researchers will test the ability of “amide proton transfer” (APT) MRI imaging to perform these vital functions and aid surgeons in treating the tumor, while sparing unaffected surrounding brain tissue. The potential new MRI technique has been show to detect “mobile cytosolic ” proteins and peptides that have weak signals.  Now the researchers will determine whether APT-MRI imaging can differentiate the normal mobile cytosolic proteins and peptides from those found in glioma. They hypothesize that APT-MRI imaging will enable clinicians to characterize primary gliomas, distinguish tumor from surrounding edema, and predict tumor grade.  They will test this imaging technique in 30 patients with suspected brain gliomas based on conventional MRI imaging and assess its accuracy by correlating the radiologic findings with tissue sample findings.

Significance: APT-MRI imaging may improve diagnostic and surgical accuracy in treating deadly brain gliomas while sparing unaffected brain tissue.

ABSTRACT

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MR Imaging of Mobile Proteins for Human Brain Tumor Detection

Clinical MRI of malignant brain tumors is currently limited in its ability to distinguish regions of viable tumor from those of peritumoral edema. Such a capability would be of importance for treatment planning and monitoring of tumor response to therapy. Proteins perform most cellular activities and have distinct levels of activity in various forms of biological tissues. We have previously demonstrated that low-concentration mobile cytosolic proteins and peptides can be detected via the water signal through exchange with their amide protons, allowing MRI of these proteins and their exchange properties. This new type of chemical exchange dependent saturation transfer-based MRI technique is called amide proton transfer (APT) imaging. We hypothesize that APT imaging of endogenous cytosolic proteins and peptides in brain tissue in vivo may provide a useful complementary MRI modality to assess tumor and peritumoral edema at the protein level for the diagnosis and monitoring of brain tumors without the need for exogenous contrast agents.

The specific aims of this application are: (1) to evaluate the uniqueness of APT imaging for characterizing primary brain tumors, (2) to determine if APT can distinguish viable tumor from peritumoral edema, and (3) to evaluate the capability of APT imaging to predict tumor grade. A total of 30 patients with brain lesions on MRI suggestive of a primary brain tumor will be recruited from the Brain Cancer Program at Johns Hopkins. Patients entering this study will undergo biopsy and/or resection as part of their standard clinical treatment plan. APT and several standard MRI sequences will be acquired on a clinical 3T MRI scanner preoperatively. The effect of APT will be determined by percent change in water intensity due to saturation transfer. We will quantify the comparison of APT imaging characteristics to FLAIR and contrast-enhanced sequences by comparing the signal intensities and tumor volumes in each of the MRI modalities. The ability of APT imaging intensity to predict tumor versus edema and tumor grade will be assessed with radiopathologic correlations. APT is a completely new MRI contrast mechanism that extends the achievable MRI contrast to the protein level. The unique features of APT imaging may provide valuable complementary information for maximizing diagnostic accuracy and guiding surgical resection of human brain tumors.

INVESTIGATOR BIOGRAPHIES

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Jinyuan Zhou, Ph.D.

Dr. Zhou earned his Ph.D. degree at Wuhan Institute of Physics, the Chinese Academy of Sciences in 1996. He was trained in the field of magnetic resonance spectroscopy (MRS). He came to the Division of MRI Research, Department of Radiology, Johns Hopkins University, as a Postdoctoral Fellow in 1997. Presently, he is an Assistant Professor of the Johns Hopkins University School of Medicine and an affiliate scientist of the F.M. Kirby Center for Functional Brain Imaging at Kennedy Krieger Institute.

Dr. Zhou’s research focuses on developing new methodologies of magnetic resonance imaging (MRI) and MRS to study brain function and physiology. His previous work about in vivo imaging included absolute quantification of cerebral blood flow, quantification of functional MRI, magnetization transfer mechanism, development of chemical exchange saturation transfer (CEST) technology, brain pH MR imaging, tissue protein MR imaging, and high-resolution diffusion tensor imaging (DTI). A major part of his recent research is in vivo imaging of experimental tumor models and clinical imaging of brain tumor patients using a new MRI technique, the amide proton transfer (APT) imaging. The overall goal is to achieve the MRI contrast at the protein level without exogenous agents and improve the diagnostic capability of MRI and the patient outcomes.

Dr. Zhou has forty-one peer-reviewed papers and one patent. He is a member of International Society of Magnetic Resonance in Medicine (ISMRM), American Association for cancer Research (AACR), and International Society for Cerebral Blood Flow and Metabolism.