Skip to main content
SpringerLink
Log in

Evaluating the Role of Amide Proton Transfer (APT)–Weighted Contrast, Optimized for Normalization and Region of Interest Selection, in Differentiation of Neoplastic and Infective Mass Lesions on 3T MRI

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the role of amide proton transfer–weighted (APT-w) magnetic resonance imaging (MRI) in differentiating neoplastic and infective mass lesions using different contrast normalizations, region of interest (ROI) selection, and histogram analysis.

Procedures

Retrospective study included 32 treatment-naive patients having intracranial mass lesions (ICMLs): low-grade glioma (LGG) = 14, high-grade glioma (HGG) = 10, and infective mass lesions = 8. APT-w MRI images were acquired along with conventional MRI images at 3 T. APT-w contrast, corrected for B0-field inhomogeneity, was computed and optimized with respect to different types of normalizations. Different ROIs on lesion region were selected followed by ROI analysis and histogram analysis. Statistical analysis was performed using Shapiro-Wilk’s test, t tests, ANOVA with Tukey’s post hoc test, and receiver operation characteristic (ROC) analysis.

Results

ICMLs showed significantly (p < 0.01) higher APT-w contrast in lesion compared with contralateral side. There was a substantial overlap between mean APT-w contrast of neoplastic and infective mass lesions as well as among different groups of ICMLs irrespective of ROI selection and normalizations. APT-w contrast (using type 4 normalization: normalized with reference signal at negative offset frequency and APT-w contrast in normal-appearing white matter) reduced variability of APT-w contrast across different subjects, and overlap was less compared with other types of normalizations. There was a significant difference (p < 0.05) between neoplastic and infective mass lesions using t test for different histogram parameters of type 4 normalized APT-w contrast. ANOVA with post hoc showed significant difference (p < 0.05) for different histogram parameters of APT-w contrast (Type 4 normalization) between LGG and HGG, LGG, and infective mass lesion. Histogram parameters such as standard deviation, mean of top percentiles, and median provided improved differentiation between neoplastic and infective mass lesions compared with mean APT-w contrast. A greater number of histogram parameters of type 4 normalized APT-w contrast corresponding to active lesion region can significantly differentiate between ICMLs than other types of normalizations and ROIs.

Conclusions

APT-w contrast using type 4 normalization and active lesion region (ROI-2) should be used for studying APT. APT-MRI should be combined with other MRI techniques to further improve the differential diagnosis of ICMLs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zhao X, Wen Z, Zhang G, Huang F, Lu S, Wang X, Hu S, Chen M, Zhou J (2013) Three-dimensional turbo-spin-echo amide proton transfer MR imaging at 3-tesla and its application to high-grade human brain tumors. Mol Imaging Biol 15:114–122

    Article  Google Scholar 

  2. Sherry AD, Woods M (2009) Chemical exchange saturation transfer contrast agents for magnetic resonance imaging. Annu Rev Biomed Eng 10:391–411

    Article  Google Scholar 

  3. 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 

  4. Liu G, Song X, Chan KWY, Mcmahon MT (2013) Nuts and bolts of chemical exchange saturation transfer MRI. NMR Biomed 26:810–828

    Article  Google Scholar 

  5. Ward KM, Aletras AH, Balaban RS (2000) A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 143:79–87

    Article  CAS  Google Scholar 

  6. Van Zijl PCM, Yadav NN (2012) Chemical exchange saturation transfer (CEST): what is in a name and what isn’t? Magn Reson Med 65:927–948

    Article  Google Scholar 

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

    Article  Google Scholar 

  8. Zhou J, Payen JF, Wilson DA et al (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 9:1085–1090

    Article  CAS  Google Scholar 

  9. Zhou J, Yan K, Zhu H (2008) A simple model for understanding the origin of the amide proton transfer MRI signal in tissue. Magn Reson Med 45:788–802

    Google Scholar 

  10. Zhou J, Heo H, Knutsson L, Van Zijl  PCM, Jiang S (2019) APT-weighted MRI: techniques, current neuro applications, and challenging issues. J Magn Reson Imaging: https://doi.org/10.1002/jmri.26645

  11. Wen Z, Hu S, Huang F, Wang X, Guo L, Quan X, Wang S, Zhou J (2010) MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. NeuroImage 51:616–622

    Article  Google Scholar 

  12. Sun PZ, Cheung J, Wang E, Lo E (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 31:1743–1750

    Article  CAS  Google Scholar 

  13. Sun PZ, Murata Y, Lu J, Wang X, Lo EH, Sorensen AG (2008) Relaxation-compensated fast multislice amide proton transfer (APT) imaging of acute ischemic stroke. Magn Reson Med 59:1175–1182

    Article  Google Scholar 

  14. Jiang S, Yu H, Wang X, Lu S, Li Y, Feng L, Zhang Y, Heo HY, Lee DH, Zhou J, Wen Z (2016) 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. J Eur Radiol 26:64–71

    Article  Google Scholar 

  15. Togao O, Yoshiura T, Keupp J, Hiwatashi A, Yamashita K, Kikuchi K, Suzuki Y, Suzuki SO, Iwaki T, Hata N, Mizoguchi M, Yoshimoto K, Sagiyama K, Takahashi M, Honda H (2014) Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro-Oncology 16:441–448

    Article  CAS  Google Scholar 

  16. Jones CK, Schlosser MJ, Van Zijl PCM et al (2006) Amide proton transfer imaging of human brain tumors at 3T. Magn Reson Med 56:585–592

    Article  Google Scholar 

  17. Debnath A, Sahoo P, Gupta P, Gupta RK, Singh A (2016) APT MRI of intracranial mass lesions at 3T and comparison with perfusion parameters. Proceedings of International Society for Magnetic Resonance in Medicine (ISMRM): 24th Annual Meeting & Exhibition, May 7-13, Singapore, program number 3712

  18. Togao O, Hiwatashi A, Yamashita K, Kikuchi K, Keupp J, Yoshimoto K, Kuga D, Yoneyama M, Suzuki SO, Iwaki T, Takahashi M, Iihara K, Honda H (2017) Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion and perfusion-weighted imaging. Eur Radiol 27:578–588

    Article  Google Scholar 

  19. Sakata A, Okada T, Yamamoto A, Kanagaki M, Fushimi Y, Okada T, Dodo T, Arakawa Y, Schmitt B, Miyamoto S, Togashi K (2015) Grading glial tumors with amide proton transfer MR imaging: different analytical approaches. J Neuro-Oncol 122:339–348

    Article  CAS  Google Scholar 

  20. Bai Y, Lin Y, Zhang W et al (2015) Noninvasive amide proton transfer magnetic resonance imaging in evaluating the grading and cellularity of gliomas. Oncotarget 8:5834–5842

    Google Scholar 

  21. Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, Knopp EA, Zagzag D (2003) Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. Am J Neuroradiol 24:1989–1998

    PubMed  Google Scholar 

  22. Singh A, Cai K, Haris M, Hariharan H, Reddy R (2013) On B 1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T. Magn Reson Med 69:818–824

    Article  CAS  Google Scholar 

  23. Kang Y, Choi SH, Kim KG (2011) Gliomas: histogram analysis of apparent diffusion coeffi cient maps with standard- or high- b-value diffusion-weighted MR imaging—correlation with tumor grade. Neuroradiology 261:882–890

    Google Scholar 

  24. Law M, Young R, Babb J, Pollack E, Johnson G (2007) Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas. Am J Neuroradiol 28:761–766

    CAS  PubMed  Google Scholar 

  25. Just N (2014) Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 111:2205–2213

    Article  CAS  Google Scholar 

  26. Tee YK, Donahue MJ, Harston GWJ et al (2013) Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration. J Magn Reson Imaging 40:832–838

    Article  Google Scholar 

  27. Zhu H, Jones CK, Van Zijl PCM et al (2010) Fast 3D chemical exchange saturation transfer (CEST) imaging of the human brain. Magn Reson Med 64:638–644

    Article  Google Scholar 

  28. Zhou J, Zhu H, Lim M, Blair L, Quinones-Hinojosa A, Messina SA, Eberhart CG, Pomper MG, Laterra J, Barker PB, van Zijl PCM, Blakeley JO (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  Google Scholar 

  29. Kim M, Gillen J, Landman BA, Zhou J, van Zijl PCM (2009) Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med 61:1441–1450

    Article  Google Scholar 

  30. Zaiss M, Schmitt B, Bachert P (2011) Quantitative separation of CEST effect from magnetization transfer and spillover effects by Lorentzian-line-fit analysis of z-spectra. J Magn Reson 211:149–155

    Article  CAS  Google Scholar 

  31. Mehnert A, Jackway P (1997) An improved seeded region growing algorithm. Pattern Recogn Lett 18:1065–1071

    Article  Google Scholar 

  32. Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, Wang S, Yan K, Fu DX, Ford E, Tyler B, Blakeley J, Laterra J, van Zijl PCM (2011) Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med 17:130–134

    Article  CAS  Google Scholar 

  33. Park JE, Kim HS, Park KJ, Kim SJ, Kim JH, Smith SA (2016) Pre and posttreatment glioma: comparison of amide proton transfer imaging with MR spectroscopy for biomarkers of tumor proliferation. Radiology 278:514–523

    Article  Google Scholar 

  34. Debnath A, Gupta RK, Singh A (2019) To evaluate the role of APT-w contrast, optimized for normalization and ROIs selection, in differentiating infective and neo-plastic mass lesions. Proceedings of International Society for Magnetic Resonance in Medicine (ISMRM): 27th Annual Meeting & Exhibition, April 11-16, Canada, program number 4347

  35. Jiang S, Zou T, Eberhart CG, Villalobos MAV, Heo HY, Zhang Y, Wang Y, Wang X, Yu H, du Y, van Zijl PCM, Wen Z, Zhou J (2017) Predicting IDH mutation status in grade II gliomas using amide proton transfer-weighted (APTw) MRI. Mag Reson Med 78:1100–1109

    Article  CAS  Google Scholar 

  36. Yu H, Wen X, Wu P et al (2019) Can amide proton transfer–weighted imaging differentiate tumor grade and predict Ki-67 proliferation status of meningioma? Eur Radiol 18:1–9

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  38. Debnath A, Singh A (2017) Lorentzian probabilistic sum based Z-spectrum fitting approach for computing CEST and NOE contrast and its comparison with lorentzian sum and asymmetry analysis. Proceedings of International Society for Magnetic Resonance in Medicine (ISMRM): 25th Annual Meeting & Exhibition, April 22-27, Hawaii, program number 1975

  39. Zaiss M, Xu LZ, Goerke S et al (2014) Inverse Z-spectrum analysis for spillover, MT and T1-corrected steady-state pulsed CEST-MRI-application to pH-weighted MRI of acute stroke. NMR Biomed 27:240–252

    Article  CAS  Google Scholar 

  40. Goerke S, Soehngen Y, Deshmane A et al (2019) Relaxation-compensated APT and rNOE CEST-MRI of human brain tumors at 3T. Magn Reson Med 00:1–11

    Google Scholar 

Download references

Acknowledgments

The authors acknowledge Philips India Limited for technical support in MRI data acquisition. The authors thank Dr. Jinyuan Zhou, Dr. Peter C.M. Van Zijl, and Dr. Indrajit Saha for APT sequence and Dr. Mamta Gupta for editing manuscript. The authors also thank Dr. Sunita Ahlawat and Dr. Rana Patir for pathological information.

Funding

This work was supported by MATRICS scheme, Science and Engineering Research Board, Department of Science and Technology (SERB-DST) grant number MTR_2017_001021 for overall study and National Institutes of Health (NIH) grants P41 EB015909 for APT pulse sequence.

Author information

Authors and Affiliations

  1. Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Block II, Room No. 299, New Delhi, 110016, India

    Ayan Debnath & Anup Singh

  2. Fortis Memorial Research Institute, Gurgaon, India

    Rakesh Kumar Gupta

  3. Department of Biomedical Engineering, All India Institute of Medical Sciences, New Delhi, India

    Anup Singh

Authors
  1. Ayan Debnath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rakesh Kumar Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anup Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anup Singh.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(PDF 238 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Debnath, A., Gupta, R.K. & Singh, A. Evaluating the Role of Amide Proton Transfer (APT)–Weighted Contrast, Optimized for Normalization and Region of Interest Selection, in Differentiation of Neoplastic and Infective Mass Lesions on 3T MRI. Mol Imaging Biol 22, 384–396 (2020). https://doi.org/10.1007/s11307-019-01382-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-019-01382-x

Key words

Search

Navigation