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 (SDdiff) 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 SDdiff of healthy control brains was 0.2% and did not differ significantly with each other (0.76 > P > 0.22). The within-session SDdiff 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

Automated summary

This study investigates the reproducibility of cerebral APT-CEST imaging in healthy tissue and gliomas at 3 T. The results indicate that cerebral APT-CEST shows good scan-rescan reproducibility in healthy tissue and tumors, and short-term measurement effects may be the dominant components for reproducibility.