Wei Hu1, Zhuozhi Dai1, Zhiwei Shen1, Yuanyu Shen1, Xiangyong Tang1, Zhiyan Zhang1, Gang Xiao2, Phillip Zhe Sun3, and Renhua Wu1
12nd Affilicated Hospital, Shantou University Medical College, Shantou, China, People's Republic of, 2Hanshan Normal University, Chao zhou, China, People's Republic of, 3Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States
Synopsis
The promising imaging technique of chemical exchange saturation transfer (CEST) MRI, which is sensitive to microenvironment properties including pH, metabolites, temperature, metal ions, and enzymatic activities, has been increasingly applied in vivo such as acute ischemia, infection and cancer. The aim of this work was to observe the differentiation between normal and acute kidney injury (AKI) using echo-planar imaging sequence (EPI) as well as the sensitive ratiometric methods under 7T magnetic field.Target Audience
People who acquire a taste for both chemical exchange saturation transfer MR imaging (CEST) and pH mapping based on Iopamidol.
Background
Human tissue lesions are often associated with cell internal and external disturbance of pH, and most of them showed the pHe value decreased. Therefore, detection of pH will have potential value for early diagnosis, pathological staging, and prognosis evaluation of diseases. However, previous approach for pH detection still remains some challenges, such as the poor anatomical resolution, which is difficult to overcome for accurate measurement. Iopamidol, a clinically approved X-ray contrast agent, contains two different types of amide that could be explored as a chemical exchange saturation transfer (CEST) agent for pH imaging. In this study, ratiometric method was applied to investigate the range of pH values both in normal and in AKI model by means of iopamidol. In this study, ratiometric method was applied both in normal and in AKI model by means of iopamidol.
Materlals and Methods
All the rats were randomly divided into two groups: normal group and AKI group. We build the AKI model with intramuscularly injected with 6.0 ml/kg 50% glycerol. All animals were allowed free access to food, but deprived of drinking water for 24h before injection. After that，mice were anesthetized using chloral hydrate and placed in a body coil supinely with abdomen pressurized. After calibrating the center frequency and shimming Bo field, a coronal anatomical image that contains double kidneys perfectly was obtained with the following parameter (TR=5.0s, TE=4.5s, average=8, field of view=60×60 mm, matrix=256×256, slice thickness=3 mm). Then, iopamidol (corresponding to 0.95 mg I/g body weight) was slowly injected into the kidney by means of tail vein. Before and after that, five CEST-MR images were obtained respectively with the same anatomy in the frequency offset of ±5.5, ±4.3 and 10000/300 ppm using a fat-suppressed single-shot echo-planar imaging sequence (TR=5054 ms, TE=29.3 ms, average=2, field of view=40×40 mm; matrix=64×64, slice thickness=3 mm) preceded by a 2.5 μT saturation block pulse 5s long. All the images were processed with MATLAB software and acquired pH weighted image.
Results
The pH values were usually lower in the calyx and medulla, in comparison to the cortex (Fig.1). At 5 min after the iopamidol injection, pH values calculated in the control rats show a mean renal cortical pH of 6.92±0.21, a mean renal medullary and calyx pH of 6.61±0.13 (P<0.05).In the glycerol-resulted AKI group, a significantly increase of pH values have been observed at the first day after glycerol injection compared with the control group (mean medullary and calyx pH 6.91±0.17, P <0.05).
Discussion
We assessed the potential of iopamidol, a clinically accepted X-Ray contrast agent whose chemical structure contains two kinds of available mobile protons, as pH-responsive MRI contrast agent. The two amide pools bring out different pH-responsive exchange rate, which could be used to eliminate the influence of its concentration by ratiometric approach. We confirmed that iopamidol ratiometric CEST is capable of measuring pH using EPI sequence at 7 T magnetic field, and we compared the pH-weighted maps between control group and glycerol-induced AKI group.
Conclusion
In this study, we confirmed that iopamidol ratiometric CEST is capable of measuring pH using EPI sequence at 7 T magnetic field, and we compared the pH-weighted maps both in healthy and AKI conditions. This method could be used as an important supplement for early diagnosis, pathological staging and the prognosis for which pH variation act as a biomarker. It is to be predicted that the accepted pH-sensitive approach will enable to apply to its experiment on humans and other disease as soon as possible.
Acknowledgements
This work was sponsored by the National Natural Science Foundation of China (Grant No. 81471730), and the National High Technology Research and Development Program (863 Program) of China (Program No. 2014AA021101).References
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