CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing

Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations.

Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B_1rms = 2microT, T_sat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted.

IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19q^codel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19q^ret (p < 0.021). IDH-mutant_1p/19q^ret had higher amides and amines than IDH-mutant_1p/19q^codel (p < 0.035). IDH-mutant_1p/19q^ret with AB/FS mismatch had higher amines than IDH-mutant_1p/19q^ret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19q^ret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014).

CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.