Skip to main content
Top
Published in: Molecular Imaging and Biology 4/2015

01-08-2015 | Research Article

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis

Authors: Kun Yan, Zongming Fu, Chen Yang, Kai Zhang, Shanshan Jiang, Dong-Hoon Lee, Hye-Young Heo, Yi Zhang, Robert N. Cole, Jennifer E. Van Eyk, Jinyuan Zhou

Published in: Molecular Imaging and Biology | Issue 4/2015

Login to get access

Abstract

Purpose

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors.

Procedures

Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry.

Results

There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor.

Conclusions

Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.
Appendix
Available only for authorised users
Literature
1.
go back to reference Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–96PubMedCrossRef Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–96PubMedCrossRef
2.
go back to reference Chang SM, Nelson S, Vandenberg S et al (2009) Integration of preoperative anatomic and metabolic physiologic imaging of newly diagnosed glioma. J Neuro-Oncol 92:401–15CrossRef Chang SM, Nelson S, Vandenberg S et al (2009) Integration of preoperative anatomic and metabolic physiologic imaging of newly diagnosed glioma. J Neuro-Oncol 92:401–15CrossRef
3.
go back to reference Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–72PubMedCrossRef Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–72PubMedCrossRef
4.
go back to reference Zhou J, Payen J, Wilson DA et al (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nature Med 9:1085–90PubMedCrossRef Zhou J, Payen J, Wilson DA et al (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nature Med 9:1085–90PubMedCrossRef
5.
go back to reference Zhou J, Lal B, Wilson DA et al (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50:1120–6PubMedCrossRef Zhou J, Lal B, Wilson DA et al (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50:1120–6PubMedCrossRef
6.
go back to reference Kauppinen RA, Kokko H, Williams SR (1992) Detection of mobile proteins by proton nuclear magnetic resonance spectroscopy in the guinea pig brain ex vivo and their partial purification. J Neurochem 58:967–74PubMedCrossRef Kauppinen RA, Kokko H, Williams SR (1992) Detection of mobile proteins by proton nuclear magnetic resonance spectroscopy in the guinea pig brain ex vivo and their partial purification. J Neurochem 58:967–74PubMedCrossRef
7.
8.
go back to reference Grossman R, Tyler B, Brem H et al (2012) Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging. J Neuro-Oncol 110(3):315–23CrossRef Grossman R, Tyler B, Brem H et al (2012) Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging. J Neuro-Oncol 110(3):315–23CrossRef
9.
go back to reference Zhou J, Blakeley JO, Hua J et al (2008) Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med 60:842–9PubMedCentralPubMedCrossRef Zhou J, Blakeley JO, Hua J et al (2008) Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med 60:842–9PubMedCentralPubMedCrossRef
10.
11.
go back to reference Zhao X, Wen Z, Zhang G et al (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 15:114–22PubMedCentralPubMedCrossRef Zhao X, Wen Z, Zhang G et al (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 15:114–22PubMedCentralPubMedCrossRef
12.
go back to reference Zhou J, Tryggestad E, Wen Z et al (2011) Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nature Med 17:130–4PubMedCentralPubMedCrossRef Zhou J, Tryggestad E, Wen Z et al (2011) Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nature Med 17:130–4PubMedCentralPubMedCrossRef
13.
go back to reference Hong X, Liu L, Wang M et al (2014) Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model. Neuro Oncol 16:856–67PubMedCentralPubMedCrossRef Hong X, Liu L, Wang M et al (2014) Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model. Neuro Oncol 16:856–67PubMedCentralPubMedCrossRef
14.
go back to reference Sagiyama K, Mashimo T, Togao O et al (2014) In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma. Proc Natl Acad Sci U S A 111:4542–7PubMedCentralPubMedCrossRef Sagiyama K, Mashimo T, Togao O et al (2014) In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma. Proc Natl Acad Sci U S A 111:4542–7PubMedCentralPubMedCrossRef
15.
go back to reference Burger PC, Dubois PJ, Schold SC et al (1983) Computerized tomographic and pathologic studies of the untreated, quiescent, and recurrent glioblastoma-multiforme. J Neurosurg 58(2):159–69PubMedCrossRef Burger PC, Dubois PJ, Schold SC et al (1983) Computerized tomographic and pathologic studies of the untreated, quiescent, and recurrent glioblastoma-multiforme. J Neurosurg 58(2):159–69PubMedCrossRef
16.
17.
go back to reference 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 38:1119–28PubMedCrossRef 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 38:1119–28PubMedCrossRef
18.
go back to reference Dula AN, Arlinghaus LR, Dortch RD et al (2013) Amide proton transfer imaging of the breast at 3 T: establishing reproducibility and possible feasibility assessing chemotherapy response. Magn Reson Med 70:216–24PubMedCentralPubMedCrossRef Dula AN, Arlinghaus LR, Dortch RD et al (2013) Amide proton transfer imaging of the breast at 3 T: establishing reproducibility and possible feasibility assessing chemotherapy response. Magn Reson Med 70:216–24PubMedCentralPubMedCrossRef
19.
go back to reference Togao O, Kessinger CW, Huang G et al (2013) Characterization of lung cancer by amide proton transfer (APT) imaging: an in-vivo study in an orthotopic mouse model. Plos One 8:e77019PubMedCentralPubMedCrossRef Togao O, Kessinger CW, Huang G et al (2013) Characterization of lung cancer by amide proton transfer (APT) imaging: an in-vivo study in an orthotopic mouse model. Plos One 8:e77019PubMedCentralPubMedCrossRef
20.
go back to reference 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 71:1841–53PubMedCrossRef 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 71:1841–53PubMedCrossRef
21.
go back to reference Zhao X, Wen Z, Huang F et al (2011) Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T. Magn Reson Med 66:1033–41PubMedCentralPubMedCrossRef Zhao X, Wen Z, Huang F et al (2011) Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T. Magn Reson Med 66:1033–41PubMedCentralPubMedCrossRef
22.
go back to reference Togao O, Yoshiura T, Keupp J et al (2014) Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro Oncol 16:441–8PubMedCentralPubMedCrossRef Togao O, Yoshiura T, Keupp J et al (2014) Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro Oncol 16:441–8PubMedCentralPubMedCrossRef
23.
go back to reference Chen W, Hu J (1999) Mapping brain metabolites using a double echo-filter metabolite imaging (DEFMI) technique. J Magn Reson 140:363–70PubMedCrossRef Chen W, Hu J (1999) Mapping brain metabolites using a double echo-filter metabolite imaging (DEFMI) technique. J Magn Reson 140:363–70PubMedCrossRef
24.
go back to reference van Zijl PCM, 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 49:440–9PubMedCrossRef van Zijl PCM, 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 49:440–9PubMedCrossRef
25.
go back to reference Zhou JY, Yan K, Zhu H (2012) A simple model for understanding the origin of the amide proton transfer MRI signal in tissue. Appl Magn Reson 42(3):393–402PubMedCentralPubMedCrossRef Zhou JY, Yan K, Zhu H (2012) A simple model for understanding the origin of the amide proton transfer MRI signal in tissue. Appl Magn Reson 42(3):393–402PubMedCentralPubMedCrossRef
26.
27.
go back to reference He QY, Chiu JF (2003) Proteomics in biomarker discovery and drug development. J Cell Biochem 89(5):868–86PubMedCrossRef He QY, Chiu JF (2003) Proteomics in biomarker discovery and drug development. J Cell Biochem 89(5):868–86PubMedCrossRef
29.
go back to reference Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectroscopy: a new technology for the analysis of protein expression in mammalian tissues. Nature Med 7:493–6PubMedCrossRef Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectroscopy: a new technology for the analysis of protein expression in mammalian tissues. Nature Med 7:493–6PubMedCrossRef
30.
go back to reference Hobbs SK, Shi G, Homer R et al (2003) Magnetic resonance imaging-guided proteomics of human glioblastoma multiforme. J Magn Reson Imag 18:530–6CrossRef Hobbs SK, Shi G, Homer R et al (2003) Magnetic resonance imaging-guided proteomics of human glioblastoma multiforme. J Magn Reson Imag 18:530–6CrossRef
31.
go back to reference Li J, Zhuang Z, Okamoto H et al (2006) Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers. Neurology 66:733–6PubMedCrossRef Li J, Zhuang Z, Okamoto H et al (2006) Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers. Neurology 66:733–6PubMedCrossRef
32.
go back to reference Shen J, Behrens B, Wistuba II et al (2006) Identification and validation of differences in protein levels in normal, premalignant, and malignant lung cells and tissues using high-throughput Western array and immunohischemistry. Cancer Res 66:11194–206PubMedCrossRef Shen J, Behrens B, Wistuba II et al (2006) Identification and validation of differences in protein levels in normal, premalignant, and malignant lung cells and tissues using high-throughput Western array and immunohischemistry. Cancer Res 66:11194–206PubMedCrossRef
33.
go back to reference Yan K, Fu Z, Van Eyk J, Wang S, Zhou J, editors. Identification of endogenous proteins correlated with amide proton transfer (APT) imaging contrast using proteomic analysis. Proc 19th Annual Meeting ISMRM; 2011; Montreal. Yan K, Fu Z, Van Eyk J, Wang S, Zhou J, editors. Identification of endogenous proteins correlated with amide proton transfer (APT) imaging contrast using proteomic analysis. Proc 19th Annual Meeting ISMRM; 2011; Montreal.
34.
go back to reference Tabuchi K, Moriya Y, Furuta T et al (1982) S-100 protein in human glial tumours. Qualitative and quantitative studies. Acta Neurochir (Wien) 65(3–4):239–51CrossRef Tabuchi K, Moriya Y, Furuta T et al (1982) S-100 protein in human glial tumours. Qualitative and quantitative studies. Acta Neurochir (Wien) 65(3–4):239–51CrossRef
35.
go back to reference Iwadate Y, Sakaida T, Hiwasa T et al (2004) Molecular classification and survival prediction in human gliomas based on proteome analysis. Cancer Res 64(7):2496–501PubMedCrossRef Iwadate Y, Sakaida T, Hiwasa T et al (2004) Molecular classification and survival prediction in human gliomas based on proteome analysis. Cancer Res 64(7):2496–501PubMedCrossRef
36.
go back to reference Odreman F, Vindigni M, Gonzales ML et al (2005) Proteomic studies on low- and high-grade human brain astrocytomas. J Proteome Res 4(3):698–708PubMedCrossRef Odreman F, Vindigni M, Gonzales ML et al (2005) Proteomic studies on low- and high-grade human brain astrocytomas. J Proteome Res 4(3):698–708PubMedCrossRef
37.
go back to reference Zhang RL, Tremblay TL, Mcdermid A et al (2003) Identification of differentially expressed proteins in human glioblastoma cell lines and tumors. Glia 42(2):194–208PubMedCrossRef Zhang RL, Tremblay TL, Mcdermid A et al (2003) Identification of differentially expressed proteins in human glioblastoma cell lines and tumors. Glia 42(2):194–208PubMedCrossRef
38.
go back to reference Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–50PubMedCrossRef Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–50PubMedCrossRef
39.
40.
41.
go back to reference Quesson B, Bouzier A-K, Thiaudiere E et al (1997) Magnetization transfer fast imaging of implanted glioma in the rat brain at 4.7 T: interpretation using a binary spin-bath model. J Magn Reson Imag 7:1076–83CrossRef Quesson B, Bouzier A-K, Thiaudiere E et al (1997) Magnetization transfer fast imaging of implanted glioma in the rat brain at 4.7 T: interpretation using a binary spin-bath model. J Magn Reson Imag 7:1076–83CrossRef
42.
go back to reference Heo H-Y, Zhang Y, Lee D-H, et al. (2014) Quantitative assessment of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer reference (EMR) signals: Application to a rat glioma model at 4.7 T. Magn Reson Med In press. Heo H-Y, Zhang Y, Lee D-H, et al. (2014) Quantitative assessment of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer reference (EMR) signals: Application to a rat glioma model at 4.7 T. Magn Reson Med In press.
43.
go back to reference Howe FA, Barton SJ, Cudlip SA et al (2003) Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 49:223–32PubMedCrossRef Howe FA, Barton SJ, Cudlip SA et al (2003) Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 49:223–32PubMedCrossRef
44.
go back to reference Zhou J, Hong X, Zhao X et al (2013) APT-weighted and NOE-weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses. Magn Reson Med 70:320–7PubMedCrossRef Zhou J, Hong X, Zhao X et al (2013) APT-weighted and NOE-weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses. Magn Reson Med 70:320–7PubMedCrossRef
45.
go back to reference 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 58:786–93PubMedCentralPubMedCrossRef 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 58:786–93PubMedCentralPubMedCrossRef
Metadata
Title
Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis
Authors
Kun Yan
Zongming Fu
Chen Yang
Kai Zhang
Shanshan Jiang
Dong-Hoon Lee
Hye-Young Heo
Yi Zhang
Robert N. Cole
Jennifer E. Van Eyk
Jinyuan Zhou
Publication date
01-08-2015
Publisher
Springer US
Published in
Molecular Imaging and Biology / Issue 4/2015
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-015-0828-6

Other articles of this Issue 4/2015

Molecular Imaging and Biology 4/2015 Go to the issue