Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging

Abstract

Amide proton transfer (APT) imaging is a type of chemical exchange-dependent saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide protons of endogenous mobile proteins and peptides in tissue are detected. Initial studies have shown promising results for distinguishing tumor from surrounding brain in patients, but these data were hampered by magnetic field inhomogeneity and a low signal-to-noise ratio (SNR). Here a practical six-offset APT data acquisition scheme is presented that, together with a separately acquired CEST spectrum, can provide B 0 -inhomogeneity corrected human brain APT images of sufficient SNR within a clinically relevant time frame. Data from nine brain tumor patients at 3T shows that APT intensities were significantly higher in the tumor core, as assigned by gadolinium-enhancement, than in contralateral normal-appearing white matter ( Recent progress in the field of proteomics (1-3) has shown that the biological characteristics of human gliomas and other cancers are defined by numerous proteins, and that the pathologic distinctions between normal and malignant tissues can be identified at the level of protein expression. Using in vivo proton MRS, Howe et al. (4) showed that the MRS-detectable mobile macromolecular proton concentration is higher in human brain tumors than in normal white matter (WM), and increases with tumor grade. These advances have prompted much interest in visualizing the protein content of tumors in vivo in MRI.Chemical exchange-dependent saturation transfer (CEST) has recently emerged as a new contrast mechanism for MRI (5-7) in the field of cellular and molecular imaging. This technique, which is a type of magnetization transfer (MT)imaging (8), has now evolved into several different variants as new CEST contrast agents (diamagnetic and paramagnetic) and approaches have been designed (9 -22). In one of these, dubbed amide proton transfer (APT) imaging (9 -13,23-25), endogenous cytosolic proteins and peptides are detected through saturation of the amide protons in the peptide bonds. Similar to the results of Howe et al. (4), this unique amide proton-based MRI contrast mechanism has shown promise for imaging the increase in protein and peptide content in brain tumors in animals (11), as well as in an initial study in human brain tumor patients (23). However, these preliminary human studies were confounded by a low signal-to-noise ratio (SNR; the APT effect is only a few percent of the water signal) and by local field inhomogeneity. The high sensitivity of APT to field inhomogeneity is due to the inherent approach in CEST-type imaging, where water saturation is measured as a function of transmitter frequency, producing the "z-spectra" (26) or CEST spectra (5). Such spectra are dominated by large direct water saturation around the water frequency at about 4.7 ppm in the proton spectrum and other saturation effects, such as conventional MT based on semisolid tissue structures (8). The effects of the saturation transfer of exchangeable protons to water ...

Multimodality Assessment of Brain Tumors and Tumor Recurrence

“…In an animal model, detection of amide protons by a new technique called amide proton transfer MRI was shown to provide a biomarker for tissue characterization in this situation (167). Amide proton transfer MRI is based on a contrast mechanism called chemical exchange-dependent saturation transfer (168) and can easily be incorporated into routine clinical examination without the use of exogenous contrast material (169).…”

Basics of Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging

“…Furthermore, the B 1 inhomogeneity of the RF pulse may also cause spatial variation in labeling efficiency and spillover factor [35]. Apart from the efforts in improving magnetic field inhomogeneities using hardware-based methods, such as parallel transmit technologies [36], post-processing algorithms have been developed for field inhomogeneity correction [37,38].…”

“…This method is called "water saturation shift referencing (WASSR)" approach. This method, however, would require acquisition of saturation images at 20-40 frequencies [38]. Since the SNR of CEST MRI is low, multiple acquisitions for each frequency offset of complete Z-spectra would be needed, which is not practical in the clinical setting.…”

“…Since the SNR of CEST MRI is low, multiple acquisitions for each frequency offset of complete Z-spectra would be needed, which is not practical in the clinical setting. Zhou et al demonstrated that a practical six-offset multi-acquisition method combined with a single reference Z-spectrum to acquire high-SNR CEST MRI can accomplish improved CEST MRI with B 0 inhomogeneity correction within an acceptable scanning time [38]. AB 1 -correction of CEST contrasts is crucial for the evaluation of data obtained in clinical studies at high field strengths with strong B 1 -inhomogeneities.…”

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

“…Therefore, pulsed saturation approaches are commonly used in clinical MRI scanners, wherein a train of saturation RF pulses is used with crusher gradients. Alternatively, one or multiple short saturation RF pulses are inserted into the two-dimensional or three-dimensional (3D) gradient-echo (22,23), segmented echo-planar imaging (24,25), turbo spin-echo (19,26,27) or gradient-and spin-echo image readout (12,18). This leads to accumulation of the saturation effect for slowly exchanging species, e.g., amide protons, due to a relatively short imaging TR, which is much less than the relaxation time (T1) of tissue.…”