Unraveling contributions to the Z-spectrum signal at 3.5 ppm of human brain tumors

Purpose: To evaluate the influence of the confounding factors, direct water saturation (DWS), and magnetization transfer contrast (MTC) effects on measured Z-spectra and amide proton transfer (APT) contrast in brain tumors. Methods: High-grade glioma patients were scanned using an RF saturation-encoded 3D MR fingerprinting (MRF) sequence at 3 T. For MRF reconstruction, a recurrent neural network was designed to learn free water and semisolid macromolecule parameter mappings of the underlying multiple tissue properties from saturation-transfer MRF signals. The DWS spectra and MTC spectra were synthesized by solving Bloch-McConnell equations and evaluated in brain tumors. Results: The dominant contribution to the saturation effect at 3.5 ppm was from DWS and MTC effects, but 25%–33% of the saturated signal in the gadolinium-enhancing tumor (13%–20% for normal tissue) was due to the APT effect. The APT^# signal of the gadolinium-enhancing tumor was significantly higher than that of the normal-appearing white matter (10.1% vs. 8.3% at 1 μT and 11.2% vs. 7.8% at 1.5 μT). Conclusion: The RF saturation-encoded MRF allowed us to separate contributions to the saturation signal at 3.5 ppm in the Z-spectrum. Although free water and semisolid MTC are the main contributors, significant APT contrast between tumor and normal tissues was observed.