J Korean Soc Radiol.  2016 Dec;75(6):419-433. 10.3348/jksr.2016.75.6.419.

Amide Proton Transfer Imaging in Clinics: Basic Concepts and Current and Future Use in Brain Tumors and Stroke

• Park JE
• Jahng GH
• Jeong HK

• KMID: 2360429
• DOI: http://doi.org/10.3348/jksr.2016.75.6.419

Abstract

Amide proton transfer (APT) imaging is gaining attention as a relatively new in vivo molecular imaging technique that has higher sensitivity and spatial resolution than magnetic resonance spectroscopy imaging. APT imaging is a subset of the chemical exchange saturation transfer mechanism, which can offer unique image contrast by selectively saturating protons in target molecules that get exchanged with protons in bulk water. In this review, we describe the basic concepts of APT imaging, particularly with regard to the benefit in clinics from the current literature. Clinical applications of APT imaging are described from two perspectives: in the diagnosis and monitoring of the treatment response in brain glioma by reflecting endogenous mobile proteins and peptides, and in the potential for stroke imaging with respect to tissue acidity.

MeSH Terms

Amides
Brain Neoplasms*
Brain*
Diagnosis
Glioma
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Molecular Imaging
Peptides
Protons*
Stroke*
Water
Amides
Peptides
Protons
Water

Figure

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  Fig. 1. Water signal change by saturation transfer. NMR = nuclear magnetic resonance, RF = radiofrequency

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  Fig. 2. The colored spectrum indicates the difference in CEST signals obtained at -3 ppm (green) and +3 ppm (red), where the magnetic resonance (MR) is reported in arbitrary units (AU). Reprinted from Cai et al. (3) with permission. CEST = chemical exchange saturation transfer

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  Fig. 3. For a patient with a meningioma, the APT image can be compared with different types of MR images, such as T2-weighted (T2W), T1-weighted (T1W), fractional anisotropy (FA), apparent diffusion coefficient (ADC), and directionally-encoded color (DEC) images, at 3T. Reprinted from Jones et al. (27) with permission. APT = amide proton transfer, FLAIR = fluid attenuated inversion recovery, MR = magnetic resonance, NAWM = normal-appearing white matter

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  Fig. 4. Correlation of APT asymmetry with Cho/Cr ratio on MR spectroscopy. A. Images and graphs of a 42-year-old patient with anaplastic oligodendroglioma (World Health Organization grade 3) show the process of transferring the same 1.5 cm3 from MR images to APT images, followed by histogram analysis of the APT solid (range: 28% to approximately 8%). B. The scatter plot, in which data points were fitted to the line, shows the relationship between Cho/Cr at MR spectroscopy and APT-solid measurement in the same voxel of interest in all solid lesions in all patients. Reprinted from Park et al. (47) with permission. APT = amide proton transfer, Cho/Cr = choline-to-creatine, MR = magnetic resonance, NAA = N-acetylaspartate

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  Fig. 5. These images were obtained in a 64-year-old man with a World Health Organization grade 1 tumor (hemangioblastoma). A. The contrast-enhanced T1-weighted MR image demonstrates a contrast-enhancing solid mass with a cyst in the right cerebellar hemisphere. B. The dynamic susceptibility contrast MR image shows that the normalized cerebral blood volume is remarkably high in the corresponding contrast-enhancing solid mass. C. The APT image demonstrates the APT signal intensity. D. The histogram distribution of the signal intensity is relatively low in the solid portion, but it is remarkably high in the cystic portion, suggesting a low-grade tumor. Reprinted from Park et al. (49) with permission. APT = amide proton transfer, MR = magnetic resonance

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  Fig. 6. Images obtained in a 75-year-old man with World Health Organization grade 4 tumor (glioblastoma). A. The contrast-enhanced T1-weighted MR image demonstrates a necrotic contrast-enhancing mass in the right parietal lobe. B. The DSC image shows that the nCBV is remarkably high in the corresponding contrast-enhancing solid mass. C. The APT image demonstrates the increased APT signal intensity. D. The histogram distribution is high in the solid portion and it is relatively low in the necrotic portion, suggesting a high-grade tumor. Reprinted from Park et al. (47) with permission. APT = amide proton transfer, DSC = dynamic susceptibility contrast, nCBV = normalized cerebral blood volume

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  Fig. 7. These images were obtained by CEST MR imaging of G47D-empty viruses and G47D-LRP-infected cell lysates. A. The representative MTR asym map shows phantoms that contained lysates of D74/HveC cells infected with either G47D-empty viruses (upper) or G47D-LRP (lower). B. This graph of the MTR asym induced by G47D-LRP in these cells shows that a significantly higher MTR asym (∗ p = 0.01) was observed in D74/HveC cell lysates infected with G47D-LRP (1.52% ± 0.06) compared to those infected with G47D-empty viruses (1.0% ± 0.02). Reprinted from Farrar et al. (54) with permission. CEST = chemical exchange saturation transfer, LRP = lysine-rich protein, MR = magnetic resonance, MTR = magnetization transfer ratio

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  Fig. 8. This graph shows the measurement of ischemic brain metabo-lites with point-resolved spectroscopy. Reprinted from Sun et al. (57) with permission. Cho/Cr = choline-to-creatine, NAA = N-acetylaspartate, DWI = diffu-sion-weighted imaging, Glx = glutamate/glutamine, Lac = lactate, ROI = region-of-interest

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  Fig. 9. These images were obtained at one day after the onset in a patient with a right middle cerebral artery territory infarction, and the APT image (right) demonstrates that APT signal intensity is relatively low in the regions of diffusion restriction (-0.945%) compared to the contralateral normal white matter (0.457%). APT = amide proton transfer

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  Fig. 10. This is the CEST spectra of 10% (by weight) bovine serum al-bumin dissolved in phosphate-buffered saline with varying pH at 37°C. Reprinted from McVicar et al. (38) with permission. CEST = chemical exchange saturation transfer

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