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.