Amide proton transfer weighted MRI measurements yield consistent and repeatable results in patients with gliomas: a prospective test-retest study

Objectives: Chemical exchange saturation transfer (CEST) imaging has emerged as a promising imaging biomarker, but its reliability for clinical practice remains uncertain. This study aimed to investigate the robustness of CEST parameters in healthy volunteers and patients with brain tumours.

Methods: A total of n = 52 healthy volunteers and n = 52 patients with histologically confirmed glioma underwent two consecutive 3-T MRI scans separated by a 1-min break. The CEST measurements were reconstructed using two models: with and without fluid suppression and included the evaluation of both amide (amidePTw) and amine (aminePTw) offsets. Mean intensity values in healthy volunteers were compared from volumetric segmentations (VOI) of grey matter, white matter, and the whole brain. Mean intensity values in brain tumour patients were assessed from VOI of the contrast-enhancing, non-enhancing and whole tumour, as well as from the normal-appearing white matter. Test-retest reliability was assessed using ICC and Bland-Altman plots.

Results: The amidePTw/aminePTw signal intensity distribution was significantly affected by fluid suppression (p < 0.001 for each VOI). Test-retest reliability in healthy volunteers showed fair to excellent agreement (ICC = 0.53-0.74), with the highest signal intensity values observed by amidePTw (ICC = 0.73-0.74). In patients, an excellent agreement of both amidePTw and aminePTw measurements was observed across different tumour regions (ICC = 0.76-0.89), with the highest ICC for contrast-enhancing tumour measurements. Bland-Altman analysis indicated negligible systematic bias and no proportional bias in measurement errors.

Conclusion: Measurements from amide/aminePTw imaging obtained from an adequately powered test-retest study yield consistent and reproducible results in glioma patients, as a prerequisite for robust imaging biomarker discovery in neuro-oncology.

Key points: Question The clinical reliability of chemical exchange saturation transfer imaging remains uncertain, necessitating further investigation to establish its robustness as a biomarker in neuro-oncology. Findings This study demonstrates that amide/amine proton transfer imaging provides repeatable, high-agreement measurements in glioma patients, particularly in contrast-enhancing tumour regions. Clinical relevance This test-retest study demonstrates that chemical exchange saturation transfer imaging using two models and assessing amide and amine offsets yield consistent and repeatable results in glioma patients, as a prerequisite for robust imaging biomarker discovery for neuro-oncology studies and clinical practice.