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A physical phantom for amine chemical exchange saturation transfer (CEST) MRI

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Abstract

Objective

To develop a robust amine chemical exchange saturation transfer (CEST) physical phantom, validate the temporal stability, and create a supporting software for automatic image processing and quality assurance.

Materials and methods

The phantom was designed as an assembled laser-cut acrylic rack and 18 vials of phantom solutions, prepared with different pHs, glycine concentrations, and gadolinium concentrations. We evaluated glycine concentrations using ultraviolet absorbance for 70 days and measured the pH, relaxation rates, and CEST contrast for 94 days after preparation. We used Spearman’s correlation to determine if glycine degraded over time. Linear regression and Bland–Altman analysis were performed between baseline and follow-up measurements of pH and MRI properties.

Results

No degradation of glycine was observed (p > 0.05). The pH and MRI measurements stayed stable for 3 months and showed high consistency across time points (R2 = 1.00 for pH, R1, R2, and CEST contrast), which was further validated by the Bland–Altman plots. Examples of automatically generated reports are provided.

Discussion

We designed a physical phantom for amine CEST-MRI, which is easy to assemble and transfer, holds 18 different solutions, and has excellent short-term chemical and MRI stability. We believe this robust phantom will facilitate the development of novel sequences and cross-scanners validations.

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Data availability

The CAD files used for creating the physical phantom components are available on (Github website: https://github.com/Jingwen-Yao/CEST_physical_phantom). MATLAB code of the automatic quality assurance software, and the accompanying template data used in this study are available on (Github website: https://github.com/Jingwen-Yao/CEST_physical_phantom).

References

  1. Vinogradov E, Sherry AD, Lenkinski RE (2013) CEST: from basic principles to applications, challenges and opportunities. J Magn Reson 229:155–172

    Article  CAS  Google Scholar 

  2. van Zijl PCM, Yadav NN (2011) Chemical exchange saturation transfer (CEST): what is in a name and what isn’t? Magn Reson Med 65(4):927–948

    Article  Google Scholar 

  3. Ling W, Regatte RR, Navon G, Jerschow A (2008) Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). P Natl Acad Sci USA 105(7):2266–2270

    Article  CAS  Google Scholar 

  4. Zaiss M, Anemone A, Goerke S, Longo DL, Herz K, Pohmann R, Aime S, Rivlin M, Navon G, Golay X, Scheffler K (2019) Quantification of hydroxyl exchange of d-Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla. NMR Biomed 32(9):4113

    Article  Google Scholar 

  5. Nasrallah FA, Pages G, Kuchel PW, Golay X, Chuang KH (2013) Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI. J Cerebr Blood Flow Metab 33(8):1270–1278

    Article  CAS  Google Scholar 

  6. Xu X, Yadav NN, Knutsson L, Hua J, Kalyani R, Hall E, Laterra J, Blakeley J, Strowd R, Pomper M, Barker P, Chan K, Liu G, McMahon MT, Stevens RD, van Zijl PC (2015) Dynamic glucose-enhanced (DGE) MRI: translation to human scanning and first results in glioma patients. Tomography 1(2):105–114

    Article  Google Scholar 

  7. Xu X, Chan KWY, Knutsson L, Artemov D, Xu JD, Liu G, Kato Y, Lal B, Laterra J, McMahon MT, van Zijl PCM (2015) Dynamic glucose enhanced (DGE) MRI for combined imaging of blood–brain barrier break down and increased blood volume in brain cancer. Magn Reson Med 74(6):1556–1563

    Article  CAS  Google Scholar 

  8. Cai KJ, Haris M, Singh A, Kogan F, Greenberg JH, Hariharan H, Detre JA, Reddy R (2012) Magnetic resonance imaging of glutamate. Nat Med 18(2):302–306

    Article  CAS  Google Scholar 

  9. Cai KJ, Singh A, Roalf DR, Nanga RPR, Haris M, Hariharan H, Gur R, Reddy R (2013) Mapping glutamate in subcortical brain structures using high-resolution GluCEST MRI. NMR Biomed 26(10):1278–1284

    Article  CAS  Google Scholar 

  10. Harris RJ, Cloughesy TF, Liau LM, Nghiemphu PL, Lai A, Pope WB, Ellingson BM (2016) Simulation, phantom validation, and clinical evaluation of fast pH-weighted molecular imaging using amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) in glioma at 3 T. NMR Biomed 29(11):1563–1576

    Article  CAS  Google Scholar 

  11. Yao J, Chakhoyan A, Nathanson DA, Yong WH, Salamon N, Raymond C, Mareninov S, Lai A, Nghiemphu PL, Prins RM, Pope WB, Everson RG, Liau LM, Cloughesy TF, Ellingson BM (2019) Metabolic characterization of human IDH mutant and wild type gliomas using simultaneous pH- and oxygen-sensitive molecular MRI. Neuro Oncol. https://doi.org/10.1093/neuonc/noz078

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kogan F, Haris M, Singh A, Cai KJ, Debrosse C, Nanga RPR, Hariharan H, Reddy R (2014) Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer. Magn Reson Med 71(1):164–172

    Article  Google Scholar 

  13. Kogan F, Haris M, Debrosse C, Singh A, Nanga RP, Cai K, Hariharan H, Reddy R (2014) In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T. J Magn Reson Imaging 40(3):596–602

    Article  Google Scholar 

  14. Zhou J, Payen J-F, Wilson DA, Traystman RJ, van Zijl PC (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 9(8):1085

    Article  CAS  Google Scholar 

  15. Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PC (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50(6):1120–1126

    Article  Google Scholar 

  16. Zhou JY, Blakeley JO, Hua J, Kim M, Laterra J, Pomper MG, van Zijl PCM (2008) Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med 60(4):842–849

    Article  Google Scholar 

  17. Paech D, Windschuh J, Oberhollenzer J, Dreher C, Sahm F, Meissner JE, Goerke S, Schuenke P, Zaiss M, Regnery S, Bickelhaupt S, Baumer P, Bendszus M, Wick W, Unterberg A, Bachert P, Ladd ME, Schlemmer HP, Radbruch A (2018) Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T. Neuro Oncol 20(12):1661–1671

    Article  CAS  Google Scholar 

  18. Sun PZ, Cheung JS, Wang E, Lo EH (2011) Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke. J Cereb Blood Flow Metab 31(8):1743–1750

    Article  CAS  Google Scholar 

  19. Yan K, Fu ZM, Yang C, Zhang K, Jiang SS, Lee DH, Heo HY, Zhang Y, Cole RN, Van Eyk JE, Zhou JY (2015) Assessing amide proton transfer (APT) MRI contrast origins in 9 L gliosarcoma in the rat brain using proteomic analysis. Mol Imaging Biol 17(4):479–487

    Article  CAS  Google Scholar 

  20. Jones KM, Pollard AC, Pagel MD (2018) Clinical applications of chemical exchange saturation transfer (CEST) MRI. J Magn Reson Imaging 47(1):11–27

    Article  Google Scholar 

  21. Harris RJ, Yao J, Chakhoyan A, Raymond C, Leu K, Liau LM, Nghiemphu PL, Lai A, Salamon N, Pope WB, Cloughesy TF, Ellingson BM (2018) Simultaneous pH-sensitive and oxygen-sensitive MRI of human gliomas at 3 T using multi-echo amine proton chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI). Magn Reson Med 80(5):1962–1978

    Article  CAS  Google Scholar 

  22. Longo DL, Busato A, Lanzardo S, Antico F, Aime S (2013) Imaging the pH evolution of an acute kidney injury model by means of iopamidol, a MRI-CEST pH-responsive contrast agent. Magn Reson Med 70(3):859–864

    Article  CAS  Google Scholar 

  23. Wapler MC, Leupold J, Dragonu J, von Elverfeld D, Zaitsev M, Wallrabe U (2014) Magnetic properties of materials for MR engineering, micro-MR and beyond. J Magn Reson 242:233–242

    Article  CAS  Google Scholar 

  24. Maddah HA (2016) Polypropylene as a promising plastic: a review. Am J Polym Sci 6(1):1–11

    CAS  Google Scholar 

  25. Oh JH, Kim HG, Woo DC, Jeong HK, Lee SY, Jahng GH (2017) Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: phantom experiments. J Korean Phys Soc 70(5):545–553

    Article  CAS  Google Scholar 

  26. Chung S, Kim D, Breton E, Axel L (2010) Rapid B-1(+) mapping using a preconditioning RF pulse with TurboFLASH readout. Magn Reson Med 64(2):439–446

    Article  Google Scholar 

  27. Yao J, Ruan D, Raymond C, Liau LM, Salamon N, Pope WB, Nghiemphu PL, Lai A, Cloughesy TF, Ellingson BM (2018) Improving B0 correction for pH-weighted amine proton chemical exchange saturation transfer (CEST) imaging by use of k-means clustering and lorentzian estimation. Tomography 4(3):123–137

    Article  Google Scholar 

  28. Mcconnell JS, Mcconnell RM, Hossner LR (1993) Ultraviolet-spectra of acetic-acid, glycine, and glyphosate. Proc Ark Acad Sci 47(1993):73–76

    CAS  Google Scholar 

  29. Schuenke P, Windschuh J, Roeloffs V, Ladd ME, Bachert P, Zaiss M (2017) Simultaneous mapping of water shift and B1 (WASABI)-application to field-inhomogeneity correction of CEST MRI data. Magn Reson Med 77(2):571–580

    Article  Google Scholar 

  30. Zaiss M, Windschuh J, Paech D, Meissner JE, Burth S, Schmitt B, Kickingereder P, Wiestler B, Wick W, Bendszus M, Schlemmer HP, Ladd ME, Bachert P, Radbruch A (2015) Relaxation-compensated CEST-MRI of the human brain at 7T: Unbiased insight into NOE and amide signal changes in human glioblastoma. Neuroimage 112:180–188

    Article  Google Scholar 

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Acknowledgements

We thank the UCLA Bioengineering department to coordinate the undergraduate Capstone senior design projects and provide the mechanical workspace. We would like to acknowledge Dr. Stephanie Seidlits, teaching assistants Jonathan Massachi and Michael Bogumil, for supporting the Capstone project.

Funding

This study was funded by American Cancer Society (ACS) Research Scholar Grant (RSG-15–003-01-CCE), UCLA SPORE in Brain Cancer (NIH/NCI 1P50CA211015-01A1), and NIH/NCI (1R21CA223757-01).

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Authors and Affiliations

Authors

Contributions

Conceptualization: JY, CRG, BME; methodology: XC, ANL, HD; data acquisition: JY, CW, XC, KD, MWJL; data analysis: JY, BB, ZSK, JANP, JDP, SSR; writing—original draft preparation: JY; Writing—review and editing: BME; funding acquisition: BME; resources: DAN; supervision: BME.

Corresponding author

Correspondence to Benjamin M. Ellingson.

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Conflict of interest

Author B.M.E. is a paid consultant at companies Medicenna, MedQIA, Neosoma, Agios Pharmaceuticals, Siemens, Imaging Endpoints, Kazia/Novogen, and NW Biopharmaceuticals. He is a consultant at companies Oncoceutics, BeiGene, BBI, Tocagen, and non-profit organizations Global Coalition for Adaptive Research (GCAR) and NIH/NCI Cancer Imaging Steering Committee. Author B.M.E. also receives research grant from companies Siemens, Janssen Pharmaceuticals, VBL, and non-profit organizations National Brain Tumor Society and ACS. Author D.A.N. is a co-founder and consultant at company Katmai Pharmaceuticals and a co-founder of company Trethera Corporation. He is also a shareholder in Sofie Biosciences. Authors J.Y., C.R.G., X.C., A.N.L., H.D., C.W., K.D., M.W.J.L, B.B., Z.S.K., J.A.N.P., J.D.P., S.S.R. has no conflict of interest to disclose.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Yao, J., Wang, C., Raymond, C. et al. A physical phantom for amine chemical exchange saturation transfer (CEST) MRI. Magn Reson Mater Phy 34, 569–580 (2021). https://doi.org/10.1007/s10334-020-00902-z

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  • DOI: https://doi.org/10.1007/s10334-020-00902-z

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