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Japanese Journal of Radiology
Published in: Japanese Journal of Radiology 2/2019

01-02-2019 | Invited Review

Amide proton transfer imaging of tumors: theory, clinical applications, pitfalls, and future directions

Authors: Kiyohisa Kamimura, Masanori Nakajo, Tomohide Yoneyama, Koji Takumi, Yuichi Kumagae, Yoshihiko Fukukura, Takashi Yoshiura

Published in: Japanese Journal of Radiology | Issue 2/2019

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Abstract

Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging technique based on chemical exchange saturation transfer (CEST). APT imaging has shown promise in oncologic imaging, especially in the imaging of brain tumors. This review article illustrates the theory of CEST/APT imaging and describes the clinical utility, pitfalls, and potential for future development of APT imaging.
Literature
1.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2016.
2.
Sugahara T, Korogi Y, Kochi M, Ikushima I, Shigematu Y, Hirai T, et al. Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas. J Magn Reson Imaging. 1999;9:53–60.PubMedCrossRef
3.
Bulakbasi N, Guvenc I, Onguru O, Erdogan E, Tayfun C, Ucoz T. The added value of the apparent diffusion coefficient calculation to magnetic resonance imaging in the differentiation and grading of malignant brain tumors. J Comput Assist Tomogr. 2004;28:735–46.PubMedCrossRef
4.
Aronen HJ, Gazit IE, Louis DN, Buchbinder BR, Pardo FS, Weisskoff RM, et al. Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology. 1994;191:41–51.PubMedCrossRef
5.
Sugahara T, Korogi Y, Kochi M, Ikushima I, Hirai T, Okuda T, et al. Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas. AJR Am J Roentgenol. 1998;171:1479–86.PubMedCrossRef
6.
Ward KM, Aletras AH, Balaban RS. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson. 2000;143:79–87.PubMedCrossRef
7.
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;9:1085–90.PubMedCrossRef
8.
Zhang S, Winter P, Wu K, Sherry AD. A novel europium(III)-based MRI contrast agent. J Am Chem Soc. 2001;123:1517–8.PubMedCrossRef
9.
Aime S, Delli Castelli D, Terreno E. Highly sensitive MRI chemical exchange saturation transfer agents using liposomes. Angew Chem Int Ed Engl. 2005;44:5513–5.PubMedCrossRef
10.
Chan KW, McMahon MT, Kato Y, Liu G, Bulte JW, Bhujwalla ZM, et al. Natural d-glucose as a biodegradable MRI contrast agent for detecting cancer. Magn Reson Med. 2012;68:1764–73.PubMedCrossRefPubMedCentral
11.
Dagher A, Aletras A, Choyke P, Balaban R. Imaging of urea using chemical exchange-dependent saturation transfer at 1.5 T. J Magn Reson Imaging. 2000;12:745–8.PubMedCrossRef
12.
van Zijl PC, Jones CK, Ren J, Malloy CR, Sherry AD. MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST). Proc Natl Acad Sci USA. 2007;104:4359–64.PubMedCrossRef
13.
Ling W, Regatte RR, Navon G, Jerschow A. Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc Natl Acad Sci USA. 2008;105:2266–70.PubMedCrossRef
14.
Haris M, Cai K, Singh A, Hariharan H, Reddy R. In vivo mapping of brain myo-inositol. Neuroimage. 2011;54:2079–85.PubMedCrossRef
15.
16.
Haris M, Nanga RP, Singh A, Cai K, Kogan F, Hariharan H, et al. Exchange rates of creatine kinase metabolites: feasibility of imaging creatine by chemical exchange saturation transfer MRI. NMR Biomed. 2012;25:1305–9.PubMedCrossRef
17.
Togao O, Hiwatashi A, Keupp J, Yamashita K, Kikuchi K, Yoshiura T, et al. Amide proton transfer imaging of diffuse gliomas: effect of saturation pulse length in parallel transmission-based technique. PLoS One. 2016;11:e0155925 (Accessed May 10, 2018).PubMedCrossRefPubMedCentral
18.
Keupp J, Eggers H. (2012) Intrinsic field homogeneity correction in fast spin echo based amide proton transfer MRI. In: Proceedings of the 20th annual meeting of ISMRM, Melbourne, Australia, 2012. Abstract 4185.
19.
Dixon WT, Hancu I, Ratnakar SJ, Sherry AD, Lenkinski RE, Alsop DC. A multislice gradient echo pulse sequence for CEST imaging. Magn Reson Med. 2010;63:253–6.PubMedCrossRefPubMedCentral
20.
Ng MC, Hua J, Hu Y, Luk KD, Lam EY. Magnetization transfer (MT) asymmetry around the water resonance in human cervical spinal cord. J Magn Reson Imaging. 2009;29:523–8.PubMedCrossRefPubMedCentral
21.
Keupp J, Doneva M, Senegas J, Hey S, Eggers H. (2014) 3D fast spin-echo amide proton transfer MR with intrinsic field homogeneity correction for neuro-oncology applications. In: Proceedings of the 22nd annual meeting of ISMRM, Milan, Italy, 2014. Abstract 3150.
22.
Jones CK, Polders D, Hua J, Zhu H, Hoogduin HJ, Zhou J, et al. In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T. Magn Reson Med. 2012;67:1579–89.PubMedCrossRef
23.
Kim M, Gillen J, Landman B, Zhou JY, van Zijl PC. Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med. 2009;61:1441–50.PubMedCrossRefPubMedCentral
24.
Sun PZ, Farrar CT, Sorensen AG. Correction for artifacts induced by B0 and B1 field inhomogeneities in pH-sensitive chemical exchange saturation transfer (CEST) imaging. Magn Reson Med. 2007;58:1207–15.PubMedCrossRef
25.
Bryant RG. The dynamics of water–protein interactions. Annu Rev Biophys Biomol Struct. 1996;25:29–53.PubMedCrossRef
26.
van Zijl PC, Zhou J, Mori N, Payen JF, Wilson D, Mori S. Mechanism of magnetization transfer during on-resonance water saturation: a new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med. 2003;49:440–9.PubMedCrossRef
27.
28.
Scheidegger R, Vinogradov E, Alsop DC. Amide proton transfer imaging with improved robustness to magnetic field inhomogeneity and magnetization transfer asymmetry using saturation with frequency alternating RF irradiation. Magn Reson Med. 2011;66:1275–85.PubMedCrossRefPubMedCentral
29.
Lee JS, Regatte RR, Jerschow A. Isolating chemical exchange saturation transfer contrast from magnetization transfer asymmetry under two-frequency rf irradiation. J Magn Reson. 2012;215:56–63.PubMedCrossRef
30.
Zhang J, Zhu W, Tain R, Zhou XJ, Cai K. Improved differentiation of low-grade and high-grade gliomas and detection of tumor proliferation using APT contrast fitted from Z-spectrum. Mol Imaging Biol. 2018;20:623–31.PubMedCrossRef
31.
Yan K, Fu Z, Yang C, Zhang K, Jiang S, Lee DH, et al. Assessing amide proton transfer (APT) MRI contrast origins in 9 L gliosarcoma in the rat brain using proteomic analysis. Mol Imaging Biol. 2015;17:479–87.PubMedCrossRefPubMedCentral
32.
Li J, Zhuang Z, Okamoto H, Vortmeyer AO, Park DM, Furuta M, et al. Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers. Neurology. 2006;66:733–6.PubMedCrossRef
33.
Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. 2010;67:279–83.PubMedCrossRef
34.
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;60:842–9.PubMedCrossRefPubMedCentral
35.
Togao O, Yoshiura T, Keupp J, Hiwatashi A, Yamashita K, Kikuchi K, et al. Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro Oncol. 2014;16:441–8.PubMedCrossRef
36.
Togao O, Hiwatashi A, Yamashita K, Kikuchi K, Keupp J, Yoshimoto K, et al. Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging. Eur Radiol. 2017;27:578–88.PubMedCrossRef
37.
Choi YS, Ahn SS, Lee SK, Chang JH, Kang SG, Kim SH, et al. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. Eur Radiol. 2017;27:3181–9.PubMedCrossRefPubMedCentral
38.
Sakata A, Fushimi Y, Okada T, Arakawa Y, Kunieda T, Minamiguchi S, et al. Diagnostic performance between contrast enhancement, proton MR spectroscopy, and amide proton transfer imaging in patients with brain tumors. J Magn Reson Imaging. 2017;46:732–9.PubMedCrossRef
39.
Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372:2499–508.PubMedCrossRefPubMedCentral
40.
The Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372:2481–98.CrossRefPubMedCentral
41.
Jiang S, Zou T, Eberhart CG, Villalobos MAV, Heo HY, Zhang Y, et al. Predicting IDH mutation status in grade II gliomas using amide proton transfer-weighted (APTw) MRI. Magn Reson Med. 2017;78:1100–9.PubMedCrossRefPubMedCentral
42.
Jiang S, Yu H, Wang X, Lu S, Li Y, Feng L, et al. 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. 2016;26:64–71.PubMedCrossRef
43.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.PubMedCrossRef
44.
45.
Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med. 2011;17:130–4.PubMedCrossRef
46.
Park JE, Kim HS, Park KJ, Kim SJ, Kim JH, Smith SA. Pre- and posttreatment glioma: comparison of amide proton transfer imaging with MR spectroscopy for biomarkers of tumor proliferation. Radiology. 2016;278:514–23.PubMedCrossRef
47.
Park KJ, Kim HS, Park JE, Shim WH, Kim SJ, Smith SA. Added value of amide proton transfer imaging to conventional and perfusion MR imaging for evaluating the treatment response of newly diagnosed glioblastoma. Eur Radiol. 2016;26:4390–403.PubMedCrossRef
48.
Mehrabian H, Desmond KL, Soliman H, Sahgal A, Stanisz GJ. Differentiation between radiation necrosis and tumor progression using chemical exchange saturation transfer. Clin Cancer Res. 2017;23:3667–75.PubMedCrossRef
49.
Park JE, Lee JY, Kim HS, Oh JY, Jung SC, Kim SJ, et al. Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography. Eur Radiol. 2018;28:3285–95.PubMedCrossRef
50.
Wen Z, Hu S, Huang F, Wang X, Guo L, Quan X, et al. MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. Neuroimage. 2010;51:616–22.PubMedCrossRefPubMedCentral
51.
Wang M, Hong X, Chang CF, Li Q, Ma B, Zhang H, et al. Simultaneous detection and separation of hyperacute intracerebral hemorrhage and cerebral ischemia using amide proton transfer MRI. Magn Reson Med. 2015;74:42–50.PubMedCrossRefPubMedCentral
52.
Jeong HK, Han K, Zhou J, Zhao Y, Choi YS, Lee SK, et al. Characterizing amide proton transfer imaging in haemorrhage brain lesions using 3 T MRI. Eur Radiol. 2017;27:1577–84.PubMedCrossRef
53.
Zheng S, van der Bom IM, Zu Z, Lin G, Zhao Y, Gounis MJ. Chemical exchange saturation transfer effect in blood. Magn Reson Med. 2014;71:1082–92.PubMedCrossRef
54.
55.
Yu H, Lou H, Zou T, Wang X, Jiang S, Huang Z, et al. Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma. Eur Radiol. 2017;27:4516–24.PubMedCrossRefPubMedCentral
56.
Ross BD, Higgins RJ, Boggan JE, Knittel B, Garwood M. 31P NMR spectroscopy of the in vivo metabolism of an intracerebral glioma in the rat. Magn Reson Med. 1988;6:403–17.PubMedCrossRef
57.
Yuan J, Chen S, King AD, Zhou J, Bhatia KS, Zhang Q, et al. Amide proton transfer-weighted imaging of the head and neck at 3 T: a feasibility study on healthy human subjects and patients with head and neck cancer. NMR Biomed. 2014;27:1239–47.PubMedCrossRefPubMedCentral
58.
Takayama Y, Nishie A, Togao O, Asayama Y, Ishigami K, Ushijima Y, et al. Amide proton transfer MR imaging of endometrioid endometrial adenocarcinoma: association with histologic grade. Radiology. 2018;286:909–17.PubMedCrossRef
59.
Klomp DW, Dula AN, Arlinghaus LR, Italiaander M, Dortch RD, Zu Z, et al. Amide proton transfer imaging of the human breast at 7T: development and reproducibility. NMR Biomed. 2013;26:1271–7.PubMedCrossRefPubMedCentral
60.
Ohno Y, Yui M, Koyama H, Yoshikawa T, Seki S, Ueno Y, et al. Chemical exchange saturation transfer MR imaging: preliminary results for differentiation of malignant and benign thoracic lesions. Radiology. 2016;279:578–89.PubMedCrossRef
Metadata
Title
Amide proton transfer imaging of tumors: theory, clinical applications, pitfalls, and future directions
Authors
Kiyohisa Kamimura
Masanori Nakajo
Tomohide Yoneyama
Koji Takumi
Yuichi Kumagae
Yoshihiko Fukukura
Takashi Yoshiura
Publication date
01-02-2019
Publisher
Springer Japan
Published in
Japanese Journal of Radiology / Issue 2/2019
Print ISSN: 1867-1071
Electronic ISSN: 1867-108X
DOI
https://doi.org/10.1007/s11604-018-0787-3

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