Reproducibility of 3D chemical exchange saturation transfer (CEST) contrasts in the healthy brain at 3T

Abstract

Chemical exchange saturation transfer (CEST) imaging may provide novel contrast for the diagnosis, prognosis, and monitoring of the progression or treatment of neurological applications. However, the reproducibility of prominent CEST contrasts like amide CEST and nuclear Overhauser enhancement (NOE) CEST must be characterized in healthy brain gray matter (GM) and white matter (GM) prior to clinical implementation. The objective of this study was to characterize the reproducibility of four different CEST contrasts in the healthy human brain. Using a 3T MRI scanner, two 3D CEST scans were acquired in 12 healthy subjects (7 females, mean age (± SD) 26 ± 4 years) approximately 10 days apart. Scan-rescan reproducibility was measured for four contrasts: amine/amide concentration-independent detection (AACID), Amide*, and inverse magnetization transfer ratio (MTR_Rex) contrast for amide and NOE. Reproducibility was evaluated between- and within-subjects using coefficients of variation (CV) and the percent difference between measurements. AACID and NOE-MTR_Rex contrasts demonstrated the lowest within-subject CVs (0.8-1.2% and 1.6-2.0%, respectively), between-subject CVs (1.2-2.1% and 3.4-4.2%, respectively), and percent difference (1.2-1.4% and 2.2-2.8%, respectively) for both GM and WM. AACID and NOE-MTR_Rex contrasts demonstrated the highest reproducibility and represented stable measurements suitable for characterizing changes in brain tissue caused by pathological processes.

Keywords: Amide; CEST MRI; Gray matter; Nuclear overhauser enhancement; Reproducibility; White matter.

Fig. 1

( A) Axial T₁-weighted slice of the brain of a healthy participant corresponding to the center of the 3D CEST volume (slice 4). The same T₁-weighted axial image with overlayed, ( B) segmented gray matter (blue), white matter (red), and cerebrospinal fluid (yellow) regions of interest; ( C) amine/amide concentration independent detect (AACID) thresholded contrast map; ( D) Amide* thresholded contrast map; ( E)thresholded contrast map, and (F)thresholded contrast map.

Fig. 2

Mean values (with standard deviation) for all four contrasts for gray matter (GM) and white matter (WM) (n = 24, 12 subjects, 2 timepoints). Amine/amide concentration independent detection (AACID) and WM values are significantly greater than GM. and Amide* GM values are significantly greater than WM. ****p < 0.0001, ***p < 0.001.

Fig. 3

Axial CEST contrast maps of one slice (corresponding to the center of the 3D volume) of one healthy participant. Amine/amide concentration independent detection (AACID), Amide*, MTR_Rex(δ_amide), and MTR_Rex(δ_NOE) maps of the same healthy participant for the first scan (left column) and second scan (right column), overlayed onto the corresponding T₁-weighted axial slice (each scan approximately 10 days apart).

Fig. 4

Histograms of the four different calculated contrasts of one healthy participant (amine/amide concentration independent detection (AACID), Amide*, , and ) for both the scan (blue) and rescan (red) conditions. The top row shows the histograms for the gray matter region-of-interests (ROIs), while the bottom row shows the histograms for the white matter ROIs. The overlap of the two scans is demonstrated in the intermediate shading (purple), demonstrating the reproducibility between scans for all calculated contrasts.

Fig. 5

Bland-Altman plots depict the average of the scan and rescan mean values and the difference between the scan and rescan mean values for all contrasts and for both gray and white matter (n = 12). The solid black lines represent the mean bias, and the dotted black lines represent the ± 1.96 standard deviation lines.

Fig. 6

(A) Mean between-subject coefficients of variation (CV) for each calculated contrast for both gray matter (GM) and white matter (WM). Between-subject CV values represent the mean ± standard error of the mean across the 12 participants (averaged over the two time points). (B) Mean within-subject CV for each calculated contrast for both GM and WM. Within-subject CV values represent the mean ± standard error of the mean between the two time points (averaged across the 12 participants). (C) Mean percent difference for each calculated contrast for both GM and WM. Percent difference represents the mean ± standard error of the mean between the two time points (averaged across the 12 participants).