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Nuclear Overhauser enhancement-mediated magnetization transfer imaging in glioma with different progression at 7 T Xiangyong Tang, Zhuozhi Dai, Gang Xiao, Gen Yan, Zhiwei Shen, Tao Zhang, Guishan Zhang, Zerui Zhuang, Yuanyu Shen, Zhiyan Zhang, Wei Hu, and Renhua Wu ACS Chem. Neurosci., Just Accepted Manuscript • DOI: 10.1021/acschemneuro.6b00173 • Publication Date (Web): 28 Oct 2016 Downloaded from http://pubs.acs.org on October 30, 2016
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ACS Chemical Neuroscience
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Nuclear Overhauser enhancement-mediated magnetization transfer imaging in
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glioma with different progression at 7 T
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Xiangyong Tang a, Zhuozhi Dai
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Guishan Zhang a, Zerui Zhuang a, Yuanyu Shen a, Zhiyan Zhang a, Wei Hu a, Renhua Wu
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a,e,*
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a
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College, Shantou 515041, China
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b
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Edmonton, T6G 2V2, Canada
a,b
, Gang Xiao c, Gen Yan a, Zhiwei Shen a, Tao Zhang d,
Department of Medical Imaging, 2nd Affiliated Hospital, Shantou University Medical
Department of Biomedical Engineering, Faculty of Medicine, University of Alberta,
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c
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521041, China
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d
The First Hospital of Changsha, Changsha, Hunan, 430100, China
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e
Provincial Key Laboratory of Medical Molecular Imaging, Guangdong, Shantou
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515041, China.
Department of Mathematics and Statistics, Hanshan Normal University, Chaozhou
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Conflict of interest statement: The authors stated that there are no conflicts of interest
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regarding the publication of this article.
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Abstract
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Glioma is a malignant neoplasm affecting the central nervous system. The conventional
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approaches to diagnosis, such as T1-weighted imaging (T1WI), T2-weighted imaging
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(T2WI), and contrast-enhanced T1WI, give an oversimplified representation of anatomic
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structures. Nuclear Overhauser enhancement (NOE) imaging is a special form of
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magnetization transfer (MT) that provides a new way to detect small solute pools through
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indirect measurement of attenuated water signals, and makes it possible to probe semi-
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solid macromolecular protons. In this study, we investigated the correlation between the
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effect of NOE-mediated imaging and progression of glioma in a rat tumor model. We
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found that the NOE signal decreased in tumor region, and signal of tumor center and
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peritumoral normal tissue markedly decreased with growth of the glioma. At the same
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time, NOE signal in contralateral normal tissue dropped relatively late (at about day 16–
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20 after implanting the glioma cells). NOE imaging is a new contrast method that may
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provide helpful insights into the pathophysiology of glioma with regard to mobile
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proteins, lipids, and other metabolites. Further, NOE images differentiate normal brain
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tissue from glioma tissue at a molecular level. Our study indicates that NOE-mediated
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imaging is a new and promising approach for estimation of tumor progression.
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Key words: magnetization transfer, chemical exchange saturation transfer, nuclear
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Overhauser enhancement, glioma
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Introduction
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Magnetization transfer (MT) imaging is a popular technique used in magnetic resonance
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imaging (MRI). Chemical exchange saturation transfer (CEST), a specific type of MT
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imaging, has recently emerged as an important contrast mechanism for MRI in the field
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of cellular and molecular imaging1-6. It indirectly detects pools of exchangeable protons
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through the water signal from low-concentration exogenous or endogenous pools of
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exchangeable protons (such as amide or imino protons, amine protons, and hydroxyl
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protons) to the bulk water proton pool7,8. Irradiation offsets (ppm) around the water
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resonance frequency are set to acquire water signals. Therefore, MT spectra, also known
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as Z-spectra, are regarded as symmetric spectra around the water proton resonance.
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The CEST imaging technique has recently been divided into several types, including
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glutamate-CEST for glutamate9–11, glucogen-CEST for glucogen6,9,12, esterase enzymes
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combined with CEST for enzymes9,13,14, gene expression-CEST for genes9,15, amide
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proton transfer (APT)-CEST for proteins and peptides6,10,16 and so on. Among these
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variations, APT imaging has unlimited potential to detect the pH microenvironment in
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tissue22 and concentrations of endogenous mobile proteins and peptides23,24. Nuclear
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Overhauser enhancement (NOE) for proteins, lipids, and other metabolites6,17–21, is also a
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type of MT imaging. NOE and CEST can be observed by the same MRI sequence.
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Although its precise mechanism is still unknown, NOE can be observed at ultrahigh
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magnetic fields21,25, and deserves further exploration as a method of evaluating tumor
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progression.
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It is widely known that glioma accounts for the majority of neoplasms occurring in the
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central nervous system (CNS)26,27. Currently, the diagnosis of CNS tumors relies mainly
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on radiology examination, and on occasions is still a conundrum without pathologic
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evidence. The most popular MRI techniques used initially for diagnosis of a CNS tumor
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are T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and T1-weighted
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gadolinium contrast-enhanced MRI. However, the limitations of these imaging
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approaches are being increasingly recognized. For example, contrast-enhanced MRI only
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partly depicts portions of the tumor due to disruption of the blood-brain barrier, and
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provides limited information on some non-enhancing supratentorial gliomas1,28-30. These
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imaging methods can describe the anatomic structure, but cannot provide any other
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information, especially at the molecular level. However, NOE imaging is a molecular
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MRI method with the ability to detecting low-concentration molecules in tissue. In the
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past few years, a number of studies have been done to detect signal variation for glioma
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with MT imaging, including NOE-mediated and APT-mediated imaging, but few studies
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have investigated the dynamic changes that occur in a growing glioma using the NOE
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technique. As we know, tumor metabolism and tumor-related molecules change as a
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tumor progresses. The purpose of this study was to observe the correlation between
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tumor progression and NOE signal strength.
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Results and discussion
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We chose a rat glioma model for magnetic resonance scanning to investigate the
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difference between NOE and APT signal strength at different B1 levels and look for a
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suitable B1 to image the NOE ratio and APT ratio (NOER and APTR). Figure 1 shows
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the Z-spectra of tumor center (TC)with different B1 values. The prominent NOE peak (at
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an offset of -2 to -5 ppm) and APT peak (at an offset of 3.5 ppm) present in the Z-spectra
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indicate that the NOE signal declined and the APT signal heightened with the increase of
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B1. When B1 is
