Reproducibility of 3 T APT‐CEST in Healthy Volunteers and Patients With Brain Glioma

BACKGROUND: Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications such as diagnosis, characterization, and treatment planning and monitoring in glioma patients. While APT‐CEST has demonstrated high potential, reproducibility remains underexplored. PURPOSE: To investigate whether cerebral APT‐CEST with clinically feasible scan time is reproducible in healthy tissue and glioma for clinical use at 3 T. STUDY TYPE: Prospective, longitudinal. SUBJECTS: Twenty‐one healthy volunteers (11 females; mean age ± SD: 39 ± 11 years) and 6 glioma patients (3 females; 50 ± 17 years: 4 glioblastomas, 1 oligodendroglioma, 1 radiologically suspected low‐grade glioma). FIELD STRENGTH/SEQUENCE: 3 T, Turbo Spin Echo ‐ ampling perfection with application optimized contrasts using different flip angle evolution ‐ chemical exchange saturation transfer (TSE SPACE‐CEST). ASSESSMENT: APT‐CEST measurement reproducibility was assessed within‐session (glioma patients, scan session 1; healthy volunteers scan sessions 1, 2, and 3), between‐sessions (healthy volunteers scan sessions 1 and 2), and between‐days (healthy volunteers, scan sessions 1 and 3). The mean APT(CEST) values and standard deviation of the within‐subject difference (SD(diff)) were calculated in whole tumor enclosed by regions of interest (ROIs) in patients, and eight ROIs in healthy volunteers—whole‐brain, cortical gray matter, putamen, thalami, orbitofrontal gyri, occipital lobes, central brain—and compared. STATISTICAL TESTS: Brown‐Forsythe tests and variance component analysis (VCA) were used to assess the reproducibility of ROIs for the three time intervals. Significance was set at P < 0.003 after Bonferroni correction. RESULTS: Intratumoral mean APT(CEST) was significantly higher than APT(CEST) in healthy‐appearing tissue in patients (0.5 ± 0.46%). The average within‐session, between‐sessions, and between‐days SD(diff) of healthy control brains was 0.2% and did not differ significantly with each other (0.76 > P > 0.22). The within‐session SD(diff) of whole‐brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. VCA showed that within‐session factors were the most important (60%) for scanning variance. DATA CONCLUSION: Cerebral APT‐CEST imaging may show good scan–rescan reproducibility in healthy tissue and tumors with clinically feasible scan times at 3 T. Short‐term measurement effects may be the dominant components for reproducibility. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2