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3D Amide Proton Transfer-Weighted Imaging for Grading Glioma and Correlating IDH Mutation Status: Added Value to 3D Pseudocontinuous Arterial Spin Labelling Perfusion

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Abstract

Purpose

The goal of this study was to evaluate the diagnostic performance of 3D amide proton transfer-weighted (3D-APTW) imaging and 3D pseudocontinuous arterial spin labelling (3D-pCASL) alone and in combination in grading gliomas (low-grade glioma (LGG) vs. high-grade glioma (HGG)) and correlating isocitrate dehydrogenase (IDH) mutation status.

Procedures

Preoperatively, 81 patients with pathologically confirmed gliomas underwent 3.0-T magnetic resonance imaging (MRI) examinations. The APTW, relative APTW (rAPTW), cerebral blood flow (CBF), and relative CBF (rCBF) values were calculated to evaluate the solid components of the tumours. The MRI parameters were compared in the classification of gliomas by independent- and paired-samples t tests. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the diagnostic performance of each parameter and the combination of the rAPTW and rCBF values.

Results

Patients with HGG showed significantly higher APTW, rAPTW, CBF, and rCBF values than those with LGG (all p < 0.001). In the ROC curve analysis, the AUC of rAPTW was the highest at 0.90. By adding the rAPTW signal to the rCBF values, the diagnostic ability of the combined parameters improved from 0.90 to 0.96. The rAPTW value yielded the highest AUC (0.92) in correlating the IDH mutation status, and the diagnostic ability improved to 0.96 by adding it to the rCBF value.

Conclusion

3D-APTW imaging combined with 3D-pCASL imaging may be used to aid assessment of grading glioma and IDH mutation status.

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Abbreviations

APTW:

Amide proton transfer-weighted

pCASL:

Pseudocontinuous arterial spin labelling

3D:

Three-dimensional

LGG:

Low-grade glioma

HGG:

High-grade glioma

CBF:

Cerebral blood flow

IDH:

Isocitrate dehydrogenase

rAPTW:

Relative amide proton transfer-weighted

rCBF:

Relative cerebral blood volume

ROC:

Receiver operating characteristic

AUC:

Area under the ROC curve

MRI:

Magnetic resonance imaging

Gd:

Gadolinium

RF:

Radiofrequency

WHO:

World Health Organization

CEST:

Chemical exchange saturation transfer

MTRasym:

Magnetization transfer asymmetry

APTWCNAWM :

APTW value of the contralateral normal-appearing white matter

CBFCNAGM :

CBF value of the contralateral normal-appearing grey matter

APTWtumour :

APTW value of the tumour

CBFtumour :

CBF value of the tumour

ICC:

Intraclass correlation coefficient

SD:

Standard deviation

ANOVA:

One-way analysis of variance

LSD:

Least significant difference

ROI:

Region of interest

rCBV:

Relative cerebral blood volume

2D:

Two-dimensional

DSC:

Dynamic susceptibility contrast

PET:

Positron-emission tomography

References

  1. Rasmussen B, Hansen S, Laursen R et al (2017) Epidemiology of glioma: clinical characteristics, symptoms, and predictors of glioma patients grade I-IV in the the Danish Neuro-Oncology Registry. J Neurooncol 135:571–579

    Article  PubMed  Google Scholar 

  2. Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820

    Article  PubMed  Google Scholar 

  3. Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sottoriva A, Spiteri I, Piccirillo SG et al (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 110:4009–4014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Scott J, Brasher PA, Sevick R et al (2002) How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology 59:947–949

    Article  CAS  PubMed  Google Scholar 

  6. Ryu YJ, Choi YH, Cheon JE et al (2018) Pediatric brain: gadolinium deposition in dentate nucleus and globus pallidus on unenhanced T1-weighted images is dependent on the type of contrast agent. Invest Radiol 53:246–255

    Article  CAS  PubMed  Google Scholar 

  7. McDonald RJ, McDonald JS, Kallmes DF et al (2017) Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 285:546–554

    Article  PubMed  Google Scholar 

  8. Jiang S, Zou T, Eberhart CG et al (2017) Predicting IDH mutation status in grade II gliomas using amide proton transfer-weighted (APTw) MRI. Magn Reson Med 78:1100–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Paech D, Windschuh J, Oberhollenzer J et al (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 20:1661–1671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Joo B, Han K, Ahn SS et al (2019) Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma. Eur Radiol 29:6643–6652

    Article  PubMed  PubMed Central  Google Scholar 

  11. Xu Z, Ke C, Liu J et al (2021) Diagnostic performance between MR amide proton transfer (APT) and diffusion kurtosis imaging (DKI) in glioma grading and IDH mutation status prediction at 3T. Eur J Radiol 134:109466

    Article  PubMed  Google Scholar 

  12. Brendle C, Hempel JM, Schittenhelm J et al (2018) Glioma grading and determination of IDH mutation status and ATRX loss by DCE and ASL perfusion. Clin Neuroradiol 28:421–428

    Article  PubMed  Google Scholar 

  13. Liu T, Cheng G, Kang X et al (2018) Noninvasively evaluating the grading and IDH1 mutation status of diffuse gliomas by three-dimensional pseudo-continuous arterial spin labeling and diffusion-weighted imaging. Neuroradiology 60:693–702

    Article  PubMed  Google Scholar 

  14. Yoo RE, Yun TJ, Hwang I et al (2020) Arterial spin labeling perfusion-weighted imaging aids in prediction of molecular biomarkers and survival in glioblastomas. Eur Radiol 30:1202–1211

    Article  CAS  PubMed  Google Scholar 

  15. Ningning D, Haopeng P, Xuefei D et al (2017) Perfusion imaging of brain gliomas using arterial spin labeling: correlation with histopathological vascular density in MRI-guided biopsies. Neuroradiology 59:51–59

    Article  PubMed  Google Scholar 

  16. Zeng Q, Jiang B, Shi F et al (2017) 3D pseudocontinuous arterial spin-labeling MR imaging in the preoperative evaluation of gliomas. AJNR Am J Neuroradiol 38:1876–1883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang N, Xie SY, Liu HM et al (2019) Arterial spin labeling for glioma grade discrimination: correlations with IDH1 genotype and 1p/19q status. Transl Oncol 12:749–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hales PW, d’Arco F, Cooper J et al (2019) Arterial spin labelling and diffusion-weighted imaging in paediatric brain tumours. Neuroimage Clin 22:101696

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Zhou J, Lal B, Wilson DA et al (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50:1120–1126

    Article  PubMed  Google Scholar 

  21. Togao O, Yoshiura T, Keupp J et al (2014) Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro Oncol 16:441–448

    Article  CAS  PubMed  Google Scholar 

  22. Zou T, Yu H, Jiang C et al (2018) Differentiating the histologic grades of gliomas preoperatively using amide proton transfer-weighted (APTW) and intravoxel incoherent motion MRI. NMR Biomed 31https://doi.org/10.1002/nbm.3850

  23. Schon S, Cabello J, Liesche-Starnecker F et al (2020) Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas. Eur J Nucl Med Mol Imaging 47:1468–1475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Durmo F, Rydhog A, Testud F et al (2020) Assessment of amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas. PLoS One 15:e0244003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhou J, Zaiss M, Knutsson L et al (2022) Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: application to brain tumors. Magn Reson Med.

  26. Keupp J, Baltes C, Harvey PR, Jvd B (2011) Parallel RF transmission based MRI technique for highly sensitive detection of amide proton transfer in the human brain at 3T. Proc Int Soc Magn Reson Med 19:710

    Google Scholar 

  27. Keupp J, Doneva M, Sénégas J et al (2014) 3D fast spin-echo amide proton transfer MR with intrinsic field homogeneity correction for neuro-oncology applications. Proc Int Soc Magn Reson Med 22:3150

    Google Scholar 

  28. 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  PubMed  Google Scholar 

  29. Jiang S, Eberhart CG, Zhang Y et al (2017) Amide proton transfer-weighted magnetic resonance image-guided stereotactic biopsy in patients with newly diagnosed gliomas. Eur J Cancer 83:9–18

    Article  PubMed  PubMed Central  Google Scholar 

  30. van Zijl PC, Zhou J, Mori N et al (2003) Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med 49:440–449

    Article  PubMed  Google Scholar 

  31. Baldewpersad Tewarie NM, Burgers IA, Dawood Y et al (2013) NADP+ -dependent IDH1 R132 mutation and its relevance for glioma patient survival. Med Hypotheses 80:728–731

    Article  CAS  PubMed  Google Scholar 

  32. Regnery S, Adeberg S, Dreher C et al (2018) Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients. Oncotarget 9:28772–28783

    Article  PubMed  PubMed Central  Google Scholar 

  33. Paech D, Dreher C, Regnery S et al (2019) Relaxation-compensated amide proton transfer (APT) MRI signal intensity is associated with survival and progression in high-grade glioma patients. Eur Radiol 29:4957–4967

    Article  PubMed  Google Scholar 

  34. Park JE, Kim HS, Park SY et al (2020) Identification of early response to anti-angiogenic therapy in recurrent glioblastoma: amide proton transfer-weighted and perfusion-weighted MRI compared with diffusion-weighted MRI. Radiology 295:397–406

    Article  PubMed  Google Scholar 

  35. Hua J, Jones CK, Blakeley J et al (2007) Quantitative description of the asymmetry in magnetization transfer effects around the water resonance in the human brain. Magn Reson Med 58:786–793

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zaiss M, Bachert P (2013) Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a review of theoretical approaches and methods. Phys Med Biol 58:R221–R269

    Article  PubMed  Google Scholar 

  37. Heo HY, Lee DH, Zhang Y et al (2017) Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging. Magn Reson Med 77:1853–1865

    Article  CAS  PubMed  Google Scholar 

  38. Zu Z (2018) Towards the complex dependence of MTRasym on T1w in amide proton transfer (APT) imaging. NMR Biomed 31:e3934

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sakata A, Okada T, Yamamoto A et al (2015) Grading glial tumors with amide proton transfer MR imaging: different analytical approaches. J Neurooncol 122:339–348

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the contribution of the research assistants (Fei Gao) and nurses (Hudie Liang, Xiuling Qiu), MR imaging technicians, and other study staff whose relentless efforts have made this study successful. Above all, we would like to thank all the patients who voluntarily underwent the MR imaging evaluations, without which this study would not have been possible.

Author information

Authors and Affiliations

  1. Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China

    Huimin Hou, Yanzhao Diao, Li Zhang & Zhenguo Yuan

  2. Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China

    Huimin Hou, Yanzhao Diao, Li Zhang & Zhenguo Yuan

  3. Department of Radiology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, 264200, Shandong, China

    Huimin Hou, Liming Wang, Min Xu & Jinchao Yu

  4. Philips Healthcare, Shanghai, China

    Weibo Chen & Yuhan Wang

  5. Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China

    Tao Song

  6. Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China

    Tao Song

  7. Department of Pathology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China

    Yu Liu

Authors
  1. Huimin Hou
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Contributions

We acknowledge all authors who have contributed significantly to this study and that all authors agree with the content of the manuscript. In keeping with the latest guidelines of the International Committee of Medical Journal Editors, the contribution of each author is presented as follows:

1. Huimin Hou contributed to the study concept and design, acquisition of data, analysis and interpretation of data, and drafting of the manuscript.

2. Zhenguo Yuan contributed to the study concept and design, interpretation of data, critical revision of the manuscript for important intellectual content, and final approval of the version to be published.

3. Yanzhao Diao, Yuhan Wang, Li Zhang, Min Xu, and Jinchao Yu contributed to the acquisition, analysis, and interpretation of the data.

4. Weibo Chen and Liming Wang contributed to the investigation, supervision, and interpretation of the data.

5. Tao Song and Yu Liu contributed to the acquisition of clinical or pathological data.

Corresponding author

Correspondence to Zhenguo Yuan.

Ethics declarations

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to Participate

Written informed consent was obtained from all individual participants included in the study.

Consent to Publish

Patients signed informed consent regarding publication of their data and photographs.

Guarantor

The scientific guarantor of this publication is Zhenguo Yuan Ph.D., M.D.

Statistics and Biometry

No complex statistical methods were necessary for this paper.

Study Subject or Cohort Overlap

Study subjects or cohorts have not been previously reported.

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The authors declare no competing interests.

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Hou, H., Chen, W., Diao, Y. et al. 3D Amide Proton Transfer-Weighted Imaging for Grading Glioma and Correlating IDH Mutation Status: Added Value to 3D Pseudocontinuous Arterial Spin Labelling Perfusion. Mol Imaging Biol 25, 343–352 (2023). https://doi.org/10.1007/s11307-022-01762-w

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