Tomography

Vol. 3 No. 4 - Dec 2017

Tomography is a scientific journal for publication of articles in imaging research

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Imaging Lung Cancer by Using Chemical Exchange Saturation Transfer MRI With Retrospective Respiration Gating Kyle M. Jones 1 , Carol A. Stuehm 2,3 , Charles C. Hsu 4 , Phillip H. Kuo 2,3 , Mark D. Pagel 2,3 , and Edward A. Randtke 2,3 1 Department of Biomedical Engineering, University of Arizona, Tucson, AZ; 2 Department of Medical Imaging, University of Arizona, Tucson, AZ; 3 University of Arizona Cancer Center, University of Arizona, Tucson, AZ; and 4 Department of Radiation Oncology, University of Arizona, Tucson, AZ Corresponding Author: Mark D. Pagel, PhD Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, 3SCR.3642 Houston, TX 77054: E-mail: mdpagel@mdanderson.org Key Words: CEST MRI, APT MRI, lung imaging, lung cancer Abbreviations: Chemical exchange saturation transfer (CEST), magnetic resonance imaging (MRI), positron emission tomography (PET), 18 F-fluordeoxyglucose (FDG), diffusion-weighted magnetic resonance imaging (DW-MRI), computed tomography (CT), relayed nuclear Overhauser effect (rNOE), amide proton transfer (APT), Fourier transform (FT), repetition time (TR), echo time (TE), field of view (FOV), 3-dimensional (3D), magnetic resonance (MR) Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-milli- second saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.03-ppm intervals. The Fourier transform of each image was used to calculate the differ- ence in phase angle between adjacent pixels in the longitudinal direction of the respiratory motion. Addi- tional digital filtering techniques were used to evaluate the breathing cycle, which was used to construct CEST spectra from images during quiescent periods. Results from CEST MRI with and without respiration gat- ing analysis were used to evaluate the asymmetry of the magnetization transfer ratio (MTR asym ), a measure of CEST, for an egg white phantom that underwent cyclic motion, in the liver of healthy patients, as well as liver and tumor tissues of patients diagnosed with lung cancer. Retrospective respiration gating analysis pro- duced more precise measurements in all cases with significant motion compared with nongated analysis methods. Finally, a preliminary clinical study with the same respiration-gated CEST MRI method showed a large increase in MTR asym after radiation therapy, a small increase or decrease in MTR asym after chemother- apy, and mixed results with combined chemoradiation therapy. Therefore, our retrospective respiration-gated method can improve CEST MRI evaluations of tumors and organs that are affected by respiratory motion. INTRODUCTION Lung cancer is the leading cause of cancer-related death in both men and women in the United States, accounting for 27% of cancer deaths in 2014 (1). Positron emission tomography (PET) with 18 F-fluordeoxyglucose (FDG), diffusion-weighted mag- netic resonance imaging (DW-MRI), perfusion MRI, and com- puted tomography (CT) have been used to noninvasively eval- uate lung masses (2-5). Each modality has its advantages and disadvantages. For example, PET with FDG is a highly sensitive imaging technique, but FDG uptake is nonspecific to tumors, and areas of inflammation may be falsely identified as tumor tissue. DW-MRI has been shown to be successful in differenti- ating tumor tissue from peritumoral edema, but its strength in evaluating tumors remains questionable owing to the lack of studies showing pathological correlations. Registration of DW- MRI images to the biopsy site is difficult because of image distortion caused by magnetic susceptibility artifacts. Perfusion CT and MRI have been shown to distinguish malignant nodules from benign pulmonary nodules with greater specificity than assessments of FDG uptake. However, this result has been shown in only lesion sizes $16 mm, thus limiting its use to a fraction of the patient population. Additional techniques are required for evaluating lung tumors with medical imaging. Chemical exchange saturation transfer (CEST) MRI is an innovative biomedical imaging technique that provides molec- ular-level information about the tissue microenvironment (6). CEST is achieved by applying a saturation pulse at the resonance frequency of labile protons of endogenous molecules, allowing the saturated protons to exchange to the water pool, and by acquiring an image to monitor a decrease in the water signal due to the exchange of saturated protons. The decrease in the water signal is referred to as CEST contrast, which has been repre- RESEARCH ARTICLE ABSTRACT © 2017 The Authors. Published by Grapho Publications, LLC This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ISSN 2379-1381 http://dx.doi.org/10.18383/j.tom.2017.00017 TOMOGRAPHY.ORG | VOLUME 3 NUMBER 4 | DECEMBER 2017 201

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