Chemical exchange rotation transfer (CERT) on human brain at 3 Tesla

Abstract

Purpose: To test the ability of a novel pulse sequence applied in vivo at 3 Tesla to separate the contributions to the water signal from amide proton transfer (APT) and relayed nuclear Overhauser enhancement (rNOE) from background direct water saturation and semisolid magnetization transfer (MT). The lack of such signal source isolation has confounded conventional chemical exchange saturation transfer (CEST) imaging.

Methods: We quantified APT and rNOE signals using a chemical exchange rotation transfer (CERT) metric, MTR_double . A range of duty cycles and average irradiation powers were applied, and results were compared with conventional CEST analyses using asymmetry (MTR_asym ) and extrapolated magnetization transfer (EMR).

Results: Our results indicate that MTR_double is more specific than MTR_asym and, because it requires as few as 3 data points, is more rapid than methods requiring a complete Z-spectrum, such as EMR. In white matter, APT (1.5 ± 0.5%) and rNOE (2.1 ± 0.7%) were quantified by using MTR_double with a 30% duty cycle and a 0.5-µT average power. In addition, our results suggest that MTR_double is insensitive to B₀ inhomogeneity, further magnifying its speed advantage over CEST metrics that require a separate B₀ measurement. However, MTR_double still has nontrivial sensitivity to B₁ inhomogeneities.

Conclusion: We demonstrated that MTR_double is an alternative metric to evaluate APT and rNOE, which is fast, robust to B₀ inhomogeneity, and easy to process.

Keywords: APT; CERT; CEST; chemical exchange; rNOE.

Figure 1

Z-spectra of CERT (A) and MTR_double (B) were obtained with an average power of 0.5 µT and a duty cycle of 30% under the constraint in Eq. 1, and the signals were averaged from 30 voxels in WM from one of the subjects. APT and rNOE signal contributions are clear, on top of a small sloping baseline.

Figure 2

A range of average irradiation powers were employed with a duty cycle of 30% (A) and 50% (B). The signals were averaged from 30 voxels in WM from six healthy subjects, respectively.

Figure 3

The comparisons of MTR_double (black), MTR_asym (blue) and sEMR¹ (red) (A) and their changes corresponding to B₀ correction (B). The results with and without WASSR B₀ correction are shown in solid and dashed lines, respectively. The signals in (A) were averaged from WM in six healthy subjects, and the signals in (B) were averaged from WM of a single subject. MTR_double was obtained with a 0.5 µT average power and a 30% duty cycle. The results show that MTR_double has (1) a much flatter and smaller baseline, (2) much more distinct and visible peaks at the exchange sites (see arrows at 3.5 and −3.5 ppm), and (3) less sensitivity to B₀ inhomogeneity than do MTR_asym and sEMR¹.

Figure 4

CEST/CERT images (A) and B₀ map (B) from one of the subject. (A) The images in the first and second columns are with and without WASSR B₀ correction, respectively. The images in the third column are the differences between the first two columns. The histograms of “difference” images are shown in the last column. MTR_double was obtained with a 0.5 µT average power and a 30% duty cycle. The difference images are highly correlated to B₀ map (B), as expected. Note the very small magnitude of the MTR_double “difference” images, indicating a small dependency on B₀. Also note that the larger gray-matter/white-matter contrast in the MTR_asym image (compared to the MTR_double images) likely reflects contributions from non-specific and confounding contributions from the sloping and non-zero baseline.

Figure 5

Simulations of MTR_double at 3.5 ppm with B₀ (A) and B₁ (B) errors. Both simulations were obtained with a two-pool model (water and solute at 3.5 ppm). The inset in (A) expands the y-axis scale for B₀ variations between −20 and 20 Hz.