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Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development

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Abstract

Objectives

To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla.

Methods

Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2−190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis.

Results

The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R2 = 0.7−0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation.

Conclusions

Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population.

Key Points

• APTW signals followed a decreasing exponential curve with age.

• The most significant APTW changes appeared within the first year

• At maturation, larger APTW decreases and lower APTW appeared in white matter

• MTR signals followed an increasing exponential curve with age

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Abbreviations

APT:

Amide proton transfer

APTW:

APT-weighted

FLAIR:

Fluid-attenuated inversion recovery

MT:

Magnetization transfer

MTR:

Magnetization transfer ratio

WM:

White matter

References

  1. Brody BA, Kinney HC, Kloman AS, Gilles FH (1987) Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination. J Neuropathol Exp Neurol 46:283–301

    Article  CAS  PubMed  Google Scholar 

  2. Knickmeyer RC, Gouttard S, Kang C et al (2008) A structural MRI study of human brain development from birth to 2 years. J Neurosci 28:12176–12182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Geng X, Gouttard S, Sharma A et al (2012) Quantitative tract-based white matter development from birth to age 2 years. Neuroimage 61:542–557

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dietrich RB, Bradley WG, Zaragoza EJ et al (1988) MR evaluation of early myelination patterns in normal and developmentally delayed infants. AJR Am J Roentgenol 150:889–896

    Article  CAS  PubMed  Google Scholar 

  5. Bird CR, Hedberg M, Drayer BP, Keller PJ, Flom RA, Hodak JA (1989) MR assessment of myelination in infants and children: usefulness of marker sites. AJNR Am J Neuroradiol 10:731–740

    CAS  PubMed  Google Scholar 

  6. Barkovich AJ, Kjos BO, Jackson DE Jr, Norman D (1988) Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T. Radiology 166:173–180

    Article  CAS  PubMed  Google Scholar 

  7. Ballesteros MC, Hansen PE, Soila K (1993) MR imaging of the developing human brain. Part 2. Postnatal development. Radiographics 13:611–622

    Article  CAS  PubMed  Google Scholar 

  8. Ding XQ, Kucinski T, Wittkugel O et al (2004) Normal brain maturation characterized with age-related T2 relaxation times: an attempt to develop a quantitative imaging measure for clinical use. Investig Radiol 39:740–746

    Article  Google Scholar 

  9. Forbes KP, Pipe JG, Bird CR (2002) Changes in brain water diffusion during the 1st year of life. Radiology 222:405–409

    Article  PubMed  Google Scholar 

  10. Laule C, Vavasour IM, Kolind SH et al (2007) Magnetic resonance imaging of myelin. Neurotherapeutics 4:460–484

    Article  CAS  PubMed  Google Scholar 

  11. Welker KM, Patton A (2012) Assessment of normal myelination with magnetic resonance imaging. Semin Neurol 32:15–28

    Article  PubMed  Google Scholar 

  12. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315

    Article  CAS  PubMed  Google Scholar 

  13. Deoni SC, Mercure E, Blasi A et al (2011) Mapping infant brain myelination with magnetic resonance imaging. J Neurosci 31:784–791

    Article  CAS  PubMed  Google Scholar 

  14. Huang H, Shu N, Mishra V et al (2013) Development of human brain structural networks through infancy and childhood. Cereb Cortex. doi:10.1093/cercor/bht1335

    Google Scholar 

  15. Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14:57–64

    Article  CAS  PubMed  Google Scholar 

  16. Kucharczyk W, Macdonald PM, Stanisz GJ, Henkelman RM (1994) Relaxation and magnetization transfer of white matter lipids at MR imaging: importance of cerebtosides and pH. Radiology 192:521–529

    Article  CAS  PubMed  Google Scholar 

  17. Engelbrecht V, Rassek M, Preiss S, Wald C, Modder U (1998) Age-dependent changes in magnetization transfer contrast of white matter in the pediatric brain. AJNR Am J Neuroradiol 19:1923–1929

    CAS  PubMed  Google Scholar 

  18. van Buchem MA, Steens SC, Vrooman HA et al (2001) Global estimation of myelination in the developing brain on the basis of magnetization transfer imaging: a preliminary study. AJNR Am J Neuroradiol 22:762–766

    PubMed  Google Scholar 

  19. Zhou J, Payen J, Wilson DA, Traystman RJ, van Zijl PCM (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 9:1085–1090

    Article  CAS  PubMed  Google Scholar 

  20. Zhou J, van Zijl PC (2006) Chemical exchange saturation transfer imaging and spectroscopy. Prog NMR Spectrosc 48:109–136

    Article  CAS  Google Scholar 

  21. Sherry AD, Woods M (2008) Chemical exchange saturation transfer contrast agents for magnetic resonance imaging. Annu Rev Biomed Eng 10:391–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yan K, Fu Z, Yang C et al (2015) Assessing amide proton transfer (APT) MRI contrast origins in 9L gliosarcoma in the rat brain using proteomic analysis. Mol Imaging Biol. doi:10.1007/s11307-11015-10828-11306

    PubMed  PubMed Central  Google Scholar 

  23. Zhou J, Zhu H, Lim M et al (2013) Three-dimensional amide proton transfer MR imaging of gliomas: initial experience and comparison with gadolinium enhancement. J Magn Reson Imaging 38:1119–1128

    Article  PubMed  Google Scholar 

  24. Jiang S, Yu H, Wang X et al (2015) Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla. Eur Radiol. doi:10.1007/s00330-00015-03805-00331

    Google Scholar 

  25. Harston GW, Tee YK, Blockley N et al (2015) Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging. Brain 138:36–42

    Article  PubMed  Google Scholar 

  26. Zhang Y, Heo HY, Lee DH et al (2015) Selecting the reference image for registration of CEST series. J Magn Reson Imaging. doi:10.1002/jmri.25027

    PubMed Central  Google Scholar 

  27. Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29:162–173

    Article  CAS  PubMed  Google Scholar 

  28. Wen Z, Hu S, Huang F et al (2010) MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. Neuroimage 51:616–622

    Article  PubMed  PubMed Central  Google Scholar 

  29. Barkovich AJ (2000) Concepts of myelin and myelination in neuroradiology. AJNR Am J Neuroradiol 21:1099–1109

    CAS  PubMed  Google Scholar 

  30. Rispoli P, Carzino R, Svaldo-Lanero T et al (2007) A thermodynamic and structural study of myelin basic protein in lipid membrane models. Biophys J 93:1999–2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sternberger NH, Itoyama Y, Kies MW, Webster HD (1978) Immunocytochemical method to identify basic protein in myelin-forming oligodendrocytes of newborn rat C.N.S. J Neurocytol 7:251–263

    Article  CAS  PubMed  Google Scholar 

  32. Hartman BK, Agrawal HC, Kalmbach S, Shearer WT (1979) A comparative study of the immunohistochemical localization of basic protein to myelin and oligodendrocytes in rat and chicken brain. J Comp Neurol 188:273–290

    Article  CAS  PubMed  Google Scholar 

  33. Keupp J, Baltes C, Harvey PR, van den Brink J (2011) Parallel RF transmission based MRI technique for highly sensitive detection of amide proton transfer in the human brainProc 19th Annual Meeting ISMRM, Montreal, Quebec, pp 710

  34. Zu Z, Janve VA, Xu J, Does MD, Gore JC, Gochberg DF (2013) A new method for detecting exchanging amide protons using chemical exchange rotation transfer. Magn Reson Med 69:637–647

    Article  CAS  PubMed  Google Scholar 

  35. Lee JS, Xia D, Ge Y, Jerschow A, Regatte RR (2014) Concurrent saturation transfer contrast in in vivo brain by a uniform magnetization transfer MRI. Neuroimage 95:22–28

    Article  PubMed  PubMed Central  Google Scholar 

  36. Desmond KL, Moosvi F, Stanisz GJ (2014) Mapping of amide, amine, and aliphatic peaks in the CEST spectra of murine xenografts at 7 T. Magn Reson Med 71:1841–1853

    Article  PubMed  Google Scholar 

  37. Cai K, Singh A, Poptani H et al (2015) CEST signal at 2 ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor. NMR Biomed 28:1–8

    CAS  PubMed  Google Scholar 

  38. Heo H-Y, Zhang Y, Jiang S, Lee D-H, Zhou J (2015) Quantitative assessment of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at 3 T. Magn Reson Med. doi:10.1002/mrm.25795

    Google Scholar 

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Acknowledgments

The authors thank Ms. Mary McAllister for editorial assistance. The scientific guarantor of this publication is Yun Peng, M.D., Ph.D. Dr. Jinyuan Zhou is a co-inventor on a patent at the USA Patent and Trademark Office for the APT-MRI technology that is licensed to Philips Healthcare. This patent is owned and managed by Johns Hopkins University. The other authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study has received funding from the National Natural Science Foundation of China (31271161) and from the National Institutes of Health (R01NS083425, R01EB009731, and R01CA166171). No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, diagnostic or prognostic study, performed at one institution.

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Authors and Affiliations

  1. Imaging Center, Department of Radiology, Beijing Children’s Hospital, Capital Medical University, Beijing, China

    Hong Zhang, Huiying Kang & Yun Peng

  2. Philips Healthcare, Beijing, China

    Xuna Zhao

  3. Division of MR Research, Department of Radiology, Johns Hopkins University, 600 N. Wolfe Street, Park 336, Baltimore, MD, 21287, USA

    Shanshan Jiang, Yi Zhang & Jinyuan Zhou

Authors
  1. Hong Zhang
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  2. Huiying Kang
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  3. Xuna Zhao
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  4. Shanshan Jiang
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  5. Yi Zhang
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  7. Yun Peng
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Correspondence to Jinyuan Zhou or Yun Peng.

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Zhang, H., Kang, H., Zhao, X. et al. Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development. Eur Radiol 26, 3368–3376 (2016). https://doi.org/10.1007/s00330-015-4188-z

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  • DOI: https://doi.org/10.1007/s00330-015-4188-z

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