A Simple Model for Understanding the Origin of the Amide Proton Transfer MRI Signal in Tissue

Zhou, Jinyuan; Yan, Kun; Zhu, He

doi:10.1007/s00723-011-0306-5

Cited by 37 publications

(28 citation statements)

References 25 publications

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“…Technically, APT imaging was designed to detect mobile proteins and peptides in tissue [42], while conventional MT imaging is sensitive to semi-solid macromolecules in the more solid environment of the cell [21]. In this study, the APTW signals (APTW max , APTW min , APTW max-min , and APTW mean ), the CEST total signal, and the MTR signal were compared in two different tumour lesions.…”

Section: Discussionmentioning

confidence: 99%

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

Jiang

Wang

et al. 2015

Eur Radiol

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Objectives To show the ability of using the amide-proton-transfer-weighted (APTW) MRI signals as imaging biomarkers to differentiate primary central-nervous-system lymphomas (PCNSLs) from high-grade gliomas (HGGs). Methods Eleven patients with lymphomas and 21 patients with HGGs were examined. Magnetization-transfer (MT) spectra over an offset range of ±6 ppm and the conventional MT ratio (MTR) at 15.6 ppm were acquired. The APTW signals, total chemical-exchange-saturation-transfer signal (integral between 0 and 5 ppm, CESTtotal), and MTR signal were obtained and compared between PCNSLs and HGGs. The diagnostic performance was assessed with the receiver-operating-characteristic-curve analysis. Results The PCNSLs usually showed more homogeneous APTW hyperintensity (spatially compared to the normal brain tissue) than the HGGs. The APTWmax, APTWmax-min, and CESTtotal signal intensities were significantly lower (P < 0.05, 0.001, and 0.05, respectively), while the APTWmin and MTR were significantly higher (both P < 0.01) in PCNSL lesions than in HGG lesions. The APTW values in peritumoral oedema were significantly lower for PCNSLs than for HGGs (P < 0.01). APTWmax-min had the highest area under the receiver-operating-characteristic curve (0.963) and accuracy (94.1%) in differentiating PCNSLs from HGGs. Conclusions The protein-based APTW signal would be a valuable MRI biomarker by which to identify PCNSLs and HGGs presurgically.

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Section: Discussionmentioning

confidence: 99%

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

Jiang

Wang

et al. 2015

Eur Radiol

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“…Amide proton transfer (APT) imaging (5), an important type of CEST MRI, is capable of detecting endogenous mobile proteins and peptides in tissue, such as those in the cytoplasm (6). Technically, the APT effect is usually quantified by a reduction in bulk water intensity, due to the chemical exchange of water protons with magnetically labeled backbone amide protons of endogenous mobile proteins and peptides at ~3.5 ppm downfield of the water resonance.…”

Section: Introductionmentioning

confidence: 99%

Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semisolid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at 3 Tesla

Heo

Zhang

Jiang

et al. 2015

Magnetic Resonance in Med

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Purpose To evaluate the use of three EMR methods to quantify APT and NOE signals in human glioma. Methods Eleven patients with high-grade glioma were scanned at 3 T. aEMR2 (asymmetric magnetization-transfer or MT model to fit two-sided, wide-offset data), sEMR2 (symmetric MT model to fit two-sided, wide-offset data), and sEMR1 (symmetric MT model to fit one-sided, wide-offset data) were assessed. ZEMR and experimental data at 3.5 ppm and −3.5 ppm were subtracted to calculate the APT and NOE signals (APT# and NOE#), respectively. Results The aEMR2 and sEMR1 models provided quite similar APT# signals, while the sEMR2 provided somewhat lower APT# signals. The aEMR2 had an erroneous NOE# quantification. Calculated APT# signal intensities of glioma (~4%), much larger than the values reported previously, were significantly higher than those of edema and normal tissue. Compared to normal tissue, gadolinium-enhancing tumor cores were consistently hyperintense on the APT# maps and slightly hypointense on the NOE# maps. Conclusion The sEMR1 model is the best choice for accurately quantifying APT and NOE signals. The APT-weighted hyperintensity in the tumor was dominated by the APT effect, and the MT asymmetry at 3.5 ppm is a reliable and valid metric for APT imaging of gliomas at 3 T.

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“…It was previously assumed that APT-weighted hyperintensity in gliomas and other cancers [16-20] is associated with high tumor cellularity and depends on increased mobile protein and peptide content in the tumors, as well as several other factors, such as the upfield nuclear Overhauser enhancement (NOE) effect and tissue pH [21, 22]. In principle, only mobile proteins and peptides (such as those in the cytoplasm) can result in a characteristic amide proton resonance at 8.3±0.5 ppm (or 3.5 ppm downfield from water) [23-25], enabling selective radiofrequency (RF) irradiation for APT imaging. However, which protein(s) or peptide(s) dominate APT hyperintensity in tumors is still totally unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Yan

Yang

et al. 2015

Mol Imaging Biol

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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.

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A Simple Model for Understanding the Origin of the Amide Proton Transfer MRI Signal in Tissue

Cited by 37 publications

References 25 publications

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

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

Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semisolid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at 3 Tesla

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

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