Korean Journal of Radiology

  • 제22권5호
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  • Pages.770-781
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  • 2021
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  • 1229-6929(pISSN)
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  • 2005-8330(eISSN)
대한영상의학회 (The Korean Society of Radiology)
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Added Value of Chemical Exchange-Dependent Saturation Transfer MRI for the Diagnosis of Dementia

  • Jang-Hoon Oh (Department of Biomedical Science and Technology, Graduate School, Kyung Hee University) ;
  • Bo Guem Choi (Department of Biomedical Engineering, Undergraduate School, College of Electronics and Information, Kyung Hee University) ;
  • Hak Young Rhee (Department of Neurology, Kyung Hee University Hospital at Gangdong, College of Medicine Kyung Hee University) ;
  • Jin San Lee (Department of Neurology, Kyung Hee University Hospital, Kyung Hee University) ;
  • Kyung Mi Lee (Department of Radiology, Kyung Hee University Hospital, Kyung Hee University) ;
  • Soonchan Park (Department of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine Kyung Hee University ) ;
  • Ah Rang Cho (Department of Psychiatry, Kyung Hee University Hospital at Gangdong, College of Medicine Kyung Hee University) ;
  • Chang-Woo Ryu (Department of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine Kyung Hee University ) ;
  • Key Chung Park (Department of Neurology, Kyung Hee University Hospital, Kyung Hee University) ;
  • Eui Jong Kim (Department of Radiology, Kyung Hee University Hospital, Kyung Hee University) ;
  • Geon-Ho Jahng (Department of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine Kyung Hee University )
  • 투고 : 2020.05.27
  • 심사 : 2020.09.05
  • 발행 : 2021.05.01
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초록

Objective: Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. Materials and Methods: Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTRasym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. Results: Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTRasym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTRasym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. Conclusion: CEST MRI potentially allows noninvasive image alterations in the Alzheimer's disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

키워드

과제정보

We thank Dr. Ha-Kyu Jeong at Samsung Electronics Company for his technical support and valuable advice in the application of the chemical exchange dependent saturation transfer technique and Dr. Jinyuan Zhou at Johns Hopkins University School of Medicine in Baltimore, USA for supporting the CEST sequence and for his fruitful advice. In addition, the authors thank Miss Soo-Jin Kim for providing statistical support.

참고문헌

  1. Kogan F, Hariharan H, Reddy R. Chemical Exchange Saturation Transfer (CEST) imaging: description of technique and potential clinical applications. Curr Radiol Rep 2013;1:102-114  https://doi.org/10.1007/s40134-013-0010-3
  2. Zhou J, Payen JF, Wilson DA, Traystman RJ, van Zijl PC. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 2003;9:1085-1090  https://doi.org/10.1038/nm907
  3. Oh JH, Kim HG, Woo DC, Jeong HK, Lee SY, Jahng GH. Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: phantom experiments. J Korean Phys Soc 2017;70:545-553  https://doi.org/10.3938/jkps.70.545
  4. van Zijl PC, Yadav NN. Chemical exchange saturation transfer (CEST): what is in a name and what isn't? Magn Reson Med 2011;65:927-948  https://doi.org/10.1002/mrm.22761
  5. Yadav NN, Jones CK, Hua J, Xu J, van Zijl PC. Imaging of endogenous exchangeable proton signals in the human brain using frequency labeled exchange transfer imaging. Magn Reson Med 2013;69:966-973  https://doi.org/10.1002/mrm.24655
  6. Goerke S, Milde KS, Bukowiecki R, Kunz P, Klika KD, Wiglenda T, et al. Aggregation-induced changes in the chemical exchange saturation transfer (CEST) signals of proteins. NMR Biomed 2017 Jan [Epub]. https://doi.org/10.1002/nbm.3665 
  7. Jahng GH, Choi W, Chung JJ, Kim ST, Rhee HY. Mapping exchangeable protons to monitor protein alterations in the brain of an Alzheimer's disease mouse model by using MRI. Curr Alzheimer Res 2018;15:1343-1353  https://doi.org/10.2174/1567205015666180911143518
  8. Wang R, Li SY, Chen M, Zhou JY, Peng DT, Zhang C, et al. Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study. Chin Med J (Engl) 2015;128:615-619  https://doi.org/10.4103/0366-6999.151658
  9. Zaiss M, Schmitt B, Bachert P. Quantitative separation of CEST effect from magnetization transfer and spillover effects by Lorentzian-line-fit analysis of z-spectra. J Magn Reson 2011;211:149-155  https://doi.org/10.1016/j.jmr.2011.05.001
  10. Jones CK, Huang A, Xu J, Edden RA, Schar M, Hua J, et al. Nuclear Overhauser enhancement (NOE) imaging in the human brain at 7T. Neuroimage 2013;77:114-124  https://doi.org/10.1016/j.neuroimage.2013.03.047
  11. Desmond KL, Moosvi F, Stanisz GJ. Mapping of amide, amine, and aliphatic peaks in the CEST spectra of murine xenografts at 7 T. Magn Reson Med 2014;71:1841-1853  https://doi.org/10.1002/mrm.24822
  12. Ahn HJ, Chin J, Park A, Lee BH, Suh MK, Seo SW, et al. Seoul Neuropsychological Screening Battery-dementia version (SNSB-D): a useful tool for assessing and monitoring cognitive impairments in dementia patients. J Korean Med Sci 2010;25:1071-1076  https://doi.org/10.3346/jkms.2010.25.7.1071
  13. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944  https://doi.org/10.1212/WNL.34.7.939
  14. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303-308  https://doi.org/10.1001/archneur.56.3.303
  15. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-1992  https://doi.org/10.1001/archneur.58.12.1985
  16. Zhu H, Jones CK, van Zijl PC, Barker PB, Zhou J. Fast 3D chemical exchange saturation transfer (CEST) imaging of the human brain. Magn Reson Med 2010;64:638-644  https://doi.org/10.1002/mrm.22546
  17. Zhao X, Wen Z, Huang F, Lu S, Wang X, Hu S, et al. Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T. Magn Reson Med 2011;66:1033-1041  https://doi.org/10.1002/mrm.22891
  18. Jahng GH, Oh JH. Physical modeling of chemical exchange saturation transfer imaging. Prog Med Phys 2017;28:135-143  https://doi.org/10.14316/pmp.2017.28.4.135
  19. Holmes HE, Colgan N, Ismail O, Ma D, Powell NM, O'Callaghan JM, et al. Imaging the accumulation and suppression of tau pathology using multiparametric MRI. Neurobiol Aging 2016;39:184-194  https://doi.org/10.1016/j.neurobiolaging.2015.12.001
  20. Zhou J, Blakeley JO, Hua J, Kim M, Laterra J, Pomper MG, et al. Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med 2008;60:842-849  https://doi.org/10.1002/mrm.21712
  21. Chen L, Wei Z, Chan KWY, Cai S, Liu G, Lu H, et al. Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI. Neuroimage 2019;188:380-390  https://doi.org/10.1016/j.neuroimage.2018.12.018
  22. Goerke S, Zaiss M, Kunz P, Klika KD, Windschuh JD, Mogk A, et al. Signature of protein unfolding in chemical exchange saturation transfer imaging. NMR Biomed 2015;28:906-913  https://doi.org/10.1002/nbm.3317
  23. Wells JA, O'Callaghan JM, Holmes HE, Powell NM, Johnson RA, Siow B, et al. In vivo imaging of tau pathology using multi-parametric quantitative MRI. Neuroimage 2015;111:369-378  https://doi.org/10.1016/j.neuroimage.2015.02.023
  24. Haris M, Nath K, Cai K, Singh A, Crescenzi R, Kogan F, et al. Imaging of glutamate neurotransmitter alterations in Alzheimer's disease. NMR Biomed 2013;26:386-391  https://doi.org/10.1002/nbm.2875
  25. Haris M, Singh A, Cai K, Nath K, Crescenzi R, Kogan F, et al. MICEST: a potential tool for non-invasive detection of molecular changes in Alzheimer's disease. J Neurosci Methods 2013;212:87-93  https://doi.org/10.1016/j.jneumeth.2012.09.025
  26. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, et al. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 1999;155:853-862  https://doi.org/10.1016/S0002-9440(10)65184-X
  27. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 1991;12:383-388  https://doi.org/10.1016/0165-6147(91)90609-V
  28. Chu WJ, Hetherington HP, Kuzniecky RJ, Vaughan JT, Twieg DB, Faught RE, et al. Is the intracellular pH different from normal in the epileptic focus of patients with temporal lobe epilepsy? A 31P NMR study. Neurology 1996;47:756-760  https://doi.org/10.1212/WNL.47.3.756
  29. Mandal PK, Akolkar H, Tripathi M. Mapping of hippocampal pH and neurochemicals from in vivo multi-voxel 31P study in healthy normal young male/female, mild cognitive impairment, and Alzheimer's disease. J Alzheimers Dis 2012;31 Suppl 3:S75-S86 https://doi.org/10.3233/JAD-2012-120166