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

Abstract

Purpose 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. Methods Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2μT, Tsat = 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. Results IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). Conclusions 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.

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

“…Careful interpretation is needed with post‐operative‐stage tumors with the surgical cavity filled with proteinaceous fluid, unless a fluid suppression method is used (Figure 10C and D). 56,111 To distinguish between viable tumor and proteinaceous fluid, APTw images should generally be interpreted together with anatomic MRI (such as T 2 w, fluid‐attenuated inversion recovery (FLAIR), and pre‐ and post‐contrast T 1 w), SWI, diffusion, and perfusion (including dynamic susceptibility contrast‐enhanced and dynamic contrast‐enhanced) MRI sequences that are acquired during routine clinical tumor protocols. This comparison helps, on one hand, to recognize and assign non‐tumorous signals and potential artifacts on APTw images and, on the other hand, to identify tumor viability characteristics, which are not captured by the structural and perfusion‐weighted MRI (Figure 10D).…”

“…Key abbreviations and nomenclatures used in the field of APTw imaging are listed in Table 1. Data from numerous institutions worldwide have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnoses, such as the detection and grading of tumors, 22–37 the assessment of treatment effect versus tumor recurrence, 38–45 prognosis related to tumor progression and survival, 46–48 and the identification of genetic markers 49–56 . It is worth mentioning that brain tumor patients require frequent MRI exams, and the exposure to gadolinium (Gd)‐based contrast agents has been indicated as a risk for people with moderate to advanced kidney failure and for Gd deposition in the brain 57–59 .…”

“…Data from numerous institutions worldwide have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnoses, such as the detection and grading of tumors, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] the assessment of treatment effect versus tumor recurrence, [38][39][40][41][42][43][44][45] prognosis related to tumor progression and survival, [46][47][48] and the identification of genetic markers. [49][50][51][52][53][54][55][56] It is worth mentioning that brain tumor patients require frequent MRI exams, and the exposure to gadolinium (Gd)-based contrast agents has been indicated as a risk for people with moderate to advanced kidney failure and for Gd deposition in the brain. [57][58][59] Although promising, there are several remaining challenging issues for clinical APTw imaging.…”

Differentiation of true progression from treatment response in high‐grade glioma treated with chemoradiation: a comparison study of 3D‐APTW and 3D‐PcASL imaging and DWI

“…39 To remove the artifacts caused by areas of large cysts and liquefied necrosis, a possible solution (fluid suppression) has been proposed to suppress the APTW signal of large cyst or liquefaction necrosis. 40,41 However, this APTW metric needs to be validated further. Compared with 3D-APTW imaging, the diagnostic performance of 3D-PcASL imaging showed a moderate diagnostic performance in differentiating TP from TR, and the rCBF values of the TP group were significantly higher than those of the TR group (p < 0.001), which is consistent with previous studies.…”

“…When evaluating TP or TR of glioma, APTW images should be combined with anatomic MRIs (such as T2WI, pre‐and post‐contrast T1WI, and FLAIR) to distinguish tumor recurrence from large cysts and liquefied necrosis with proteinaceous fluid 39 . To remove the artifacts caused by areas of large cysts and liquefied necrosis, a possible solution (fluid suppression) has been proposed to suppress the APTW signal of large cyst or liquefaction necrosis 40,41 . However, this APTW metric needs to be validated further.…”