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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA
Hye Rim Cho, Youkyung Lee, Philip Doble, David Bishop, Dominic Hare, Young-Jae Kim, Kwang Gi Kim, Hye Seung Jung, Kyong Soo Park, Seung Hong Choi, Woo Kyung Moon
Hye Rim Cho, Youkyung Lee, Seung Hong Choi, Woo Kyung Moon, Department of Radiology, Seoul National University College of Medicine, Seoul 110-744, South Korea
Hye Rim Cho, Woo Kyung Moon, Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744, South Korea
Youkyung Lee, Department of Radiology, College of Medicine, Hanyang University, Hanyang University Guri Hospital, Guri, Gyeonggi-do 471-701, South Korea
Philip Doble, David Bishop, Dominic Hare, Department of Chemistry and Forensic Science, University of Technology, Sydney, NSW 2007, Australia
Young-Jae Kim, Kwang Gi Kim, Biomedical Engineering Branch, Division of Convergence Technology, National Cancer Center, Gyeonggi-do 410-769, South Korea
Hye Seung Jung, Kyong Soo Park, Department of Internal Medicine, Seoul NationalUniversity College of Medicine, Seoul 110-744, South Korea
Seung Hong Choi, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, South Korea
Author contributions: Cho HR and Lee Y contributed equally to this work; Choi SH and Moon WK designed the research; Cho HR, Lee Y, Bishop D, Doble P, Hare D and Jung HS performed the research; Kim YJ and Kim KG contributed analytic tools; Lee Y analyzed the data and wrote the manuscript; Park KS contributed to discussion; Choi SH and Moon WK contributed to discussion and edited manuscript; Choi SH and Moon WK are the guarantors of this work, and as full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; Moon WK is a co-corresponding author.
Supported by Innovative Research Institute for Cell Therapy, Ministry for Health, Welfare and Family Affairs (A062260) in South Korea.
Ethics approval: Not Institutional Review Board approval. Institutional Review Board approval is required for human or human related study in our institution.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Seoul National University Hospital (IACUC protocol number: 11-0019).
Conflict-of-interest: The authors declare no conflict of interest.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at verocay@snuh.org or moonwk@snu.ac.kr.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Seung Hong Choi, MD, PhD, Department of Radiology, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul 110-744, South Korea. verocay@snuh.org
Telephone: +82-2-20722861 Fax: +82-2-7436385
Received: October 5, 2014
Peer-review started: October 6, 2014
First decision: November 26, 2014
Revised: January 1, 2015
Accepted: March 27, 2015
Article in press: March 27, 2015
Published online: May 21, 2015
AIM: To investigate the performance of Gadofluorine P-enhanced magnetic resonance imaging (MRI) on the diagnosis of diabetes in a streptozotocin (STZ) -induced diabetic rat model.
METHODS: Fischer 344 rats were treated with STZ. Rats not treated with STZ served as controls. T1-weighted MRI was performed using a 3T scanner before and after the injection of Gd-DOTA or Gadofluorine P (6 diabetic rats, 5 controls). The normalized signal intensity (SI) and the enhancement ratio (ER) of the pancreas were measured at each time point, and the values were compared between the normal and diabetic rats using the Mann-Whitney test. In addition, the values were correlated with the mean islet number. Optimal cut-off values were calculated using a positive test based on receiver operating characteristics. Intrapancreatic Gd concentration after the injection of each contrast media was measured using laser ablation-inductively coupled plasma-mass spectrometry in a separate set of rats (4 diabetic rats, 4 controls for Gadofluorine P; 2, 2 for Gd-DOTA).
RESULTS: The normalized SI and ER of the pancreas using Gd-DOTA were not significantly different between diabetic rats and controls. With Gadofluorine P, the values were significantly higher in the diabetic rats than in the control rats 30 min after injection (P < 0.05). The area under the receiver operating characteristic curve that differentiated diabetic rats from the control group was greater for Gadofluorine P than for Gd-DOTA (0.967 vs 0.667, P = 0.085). An increase in normalized SI 30 min after Gadofluorine P was correlated with a decrease in the mean number of islets (r2 = 0.510, P = 0.014). Intra-pancreatic Gd was higher in rats with Gadofluorine P injection than Gd-DOTA injection (Gadofluorine P vs Gd-DOTA, 7.37 vs 0.00, P < 0.01). A significant difference in the concentration of intrapancreatic Gd was observed between the control and diabetic animals that were sacrificed 30 min after Gadofluorine P injection (control vs diabetic, 3.25 ng/g vs 10.55 ng/g, P < 0.05)
CONCLUSION: In this STZ-induced diabetes rat model, Gadofluorine P-enhanced MRI of the pancreas showed high accuracy in the diagnosis of diabetes.
Core tip: Early changes in type 1 diabetes involve islet microvasculature such that vascular permeability increases. We used noninvasive magnetic resonance imaging to image, in vivo, the vasculature of the pancreas in streptozotocin-induced diabetic rats using Gadofluorine P. We anticipate that with further development, this technique could diagnose type 1 diabetes early, as well as monitor vascular and islet changes noninvasively and quantitatively.
