3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T

Abstract

Purpose: For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal-to-noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z-spectrum, which increases scan duration. This article proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z-spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost.

Methods: A 3D snapshot CEST sequence was optimized for low-power CEST MRI at 3T. Pulsed saturation was optimized for saturation power and saturation duration. Spectral sampling and postprocessing (B₀ correction, denoising) was optimized for spectrally selective Lorentzian CEST effect extraction. Reproducibility was demonstrated in 3 healthy volunteers and feasibility was shown in 1 tumor patient.

Results: Low-power saturation was achieved by a train of 80 pulses of duration t_p = 20 ms (total saturation time t_sat = 3.2 seconds at 50% duty cycle) with B₁ = 0.6 μT at 54 irradiation frequency offsets. With the 3D snapshot CEST sequence, a 180 × 220 × 54 mm field of view was acquired in 7 seconds per offset. Spectrally selective CEST effects at +3.5 and -3.5 ppm were quantified using multi-Lorentzian fitting. Reproducibility was high with an intersubject coefficient of variation below 10% in CEST contrasts. Amide and nuclear overhauser effect CEST effects showed similar correlations in tumor and necrosis as show in previous ultra-high field work.

Conclusion: A sophisticated CEST tool ready for clinical application was developed and tested for feasibility.

Keywords: APT; NOE; brain tumor; chemical exchange saturation transfer; magnetization transfer.

Figure 1

Contrast optimization. B₁ dispersion of Z‐spectra (A,B) and MTR_LD effects (C,D) in gray matter (GM) and white matter (WM) show that higher power with shorter pulses broadens the CEST peaks. Spectrally selective CEST effects are maximized at 0.8 μT, whereas GM‐WM contrast at +3.5, +2, and –3.5 ppm is maximized at 0.6 to 0.7 μT (E). The dependency of Z‐spectra (F,G) and CEST effects (H,I) on total saturation time is negligible. The same saturation and contrast can be sufficiently achieved with shorter saturation time, improving clinical feasibility. Z‐spectra and MTR_LD spectra are in arbitrary units

Figure 2

Background signal fitting. (A,B) The total background signal (blue), with contributions from direct water saturation (DS; orange) and the ssMT pool (yellow), is fitted according to Equations –4. Points between ±0.5 and ±10 ppm where CEST effects are expected to occur (crosses) were excluded from the background fit. (C,D) Fitted DS and ssMT pool amplitudes in arbitrary units

Figure 3

CEST effect fitting of Lorentzian difference spectrum (MTR_LD). The Lorentzian difference signal (Equation (5)) reveals CEST contrasts at individual offsets (A–C) and in the MTR_LD spectrum in gray and white matter segments in a single slice (D). Error bars represent standard deviation across gray and white matter voxels, respectively, in a single subject. MTR_LD is expressed in arbitrary units

Figure 4

Reproducibility in 3 healthy subjects. (A–C) Isolated CEST effects obtained from 3‐pool Lorentzian fitting of the MTR_LD spectrum (Equations (6) and (7)). Whole‐brain images are provided in Supporting Information Figure S12. The +2.0‐ppm signal is strongly influenced by direct water saturation and residual off‐resonance effects. (D,E) Mean MTR_LD spectra in gray and white matter segments. (F) Mean and standard deviation across subjects of fitted CEST effects in gray and white matter segments of a single slice. Slices were selected to have similar gray and white matter segments for each subject. Gray matter and white matter signals are clearly distinguishable for the +3.5‐ppm, –3.5‐ppm, and ssMT pools, with coefficient of variation for each pool and each ROI printed above each bar. MTR_LD spectra and fitted pool amplitudes are expressed in arbitrary units

Figure 5

Comparison of spectrally selective CEST effects at 3 and 9.4T. (A,B) Z‐spectra acquired at 3T show broader, coalesced effects compared to those acquired with similar saturation parameters at 9.4T. Still, fitted CEST contrast at 3T (C) shows similar distribution as observed at 9.4T (D), confirming spectral selectivity and indicating detectable effect size at +3.5 and –3.5 ppm. UHF strengths provide much higher SNR in comparison to 3T. Denoising 3T data allows for comparable contrast. Z‐spectra and fitted pool amplitudes are expressed in arbitrary units

Figure 6

Isolated CEST effects in a patient with a brain tumor for a single slice. Images from surrounding slices are provided in Supporting Information Figure S14. Postcontrast T₁‐weighted images show gadolinium ring enhancement, which coincides with hyperintensity at +3.5 ppm and isointensity at –3.5 ppm, and T₁ hypointensity corresponding to reduced signal in ssMT and –3.5‐ppm CEST maps. All pool sizes are expressed in arbitrary units