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Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness

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Abstract

Purpose

Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness.

Procedures

Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1 = 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (1H-MRS) was performed to quantify and compare the total Cr concentration in the tumor.

Results

CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size.

Conclusions

Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

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Acknowledgments

We gratefully acknowledge the discussions with Drs. Mohammad Haris and Anup Singh from the Center for MR and Optical Imaging at University of Pennsylvania. Our sincere thanks are also due to Drs. Weixia Liu and Stephen Pickup for their imaging assistance as well as Ranjit Ittyerah and Dr. Damodar Reddy for their help with the animal model. This work was partially supported by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health through grant number P41 EB015893 and the Department of Radiology and the Center for Magnetic Resonance Research at University of Illinois at Chicago.

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Authors and Affiliations

  1. Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Kejia Cai, Rong-Wen Tain, Xiaohong Joe Zhou, Frederick C. Damen & Alessandro M. Scotti

  2. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA

    Kejia Cai, Xiaohong Joe Zhou & Alessandro M. Scotti

  3. The Center for Magnetic Resonance and Optical Imaging, Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Hari Hariharan & Ravinder Reddy

  4. Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK

    Harish Poptani

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  1. Kejia Cai
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Correspondence to Kejia Cai.

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Cai, K., Tain, RW., Zhou, X.J. et al. Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness. Mol Imaging Biol 19, 225–232 (2017). https://doi.org/10.1007/s11307-016-0995-0

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