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 ...

Background As cerebrovascular and Alzheimer’s proteinopathy have previously shown to affect cerebral blood flow (CBF) as well as cognition, CBF could be a potential early hemodynamic biomarker of cognitive decline. Here, we investigated to what extent cardiovascular risk factors and amyloid burden affect CBF in an elderly cognitively unimpaired (CU) population. Method We included 153 CU participants (minimal MMSE = 28) from the EMIF‐AD PreclinAD Twin60++ cohort (Table 1), who underwent [18F]flutemetamol PET and arterial spin labeling (ASL) MRI. Amyloid‐PET scans were visually assessed as negative or positive, upon which participants were grouped based on their longitudinal changes in amyloid positivity (visual read groups). Cortical amyloid burden was quantified with the Centiloid method globally and for 4 early amyloid accumulation regions of interest (ROIs). ASL scans were processed and quantified with ExploreASL for total gray matter (GM), and for vascular territories overlapping with the amyloid ROIs (Figure 1). Longitudinal analysis including baseline Centiloid values and yearly CBF change rates (Delta CBF) was performed for 98 participants with longitudinal imaging data available (4.23 years ± 0.43 follow‐up time). Associations between CBF and amyloid — with and without the interaction of vascular risk factors (i.e., Framingham score) — were assessed using generalized estimating equations (GEEs), both for baseline and rates of change measurements. Models were adjusted for age, sex, and twin dependency. Result While no association between amyloid burden and CBF was observed across the cohort, in participants with a high Framingham vascular risk score, higher amyloid was associated with increased CBF, for most ROIs (Table 2, Figure 2). Additionally, precuneus amyloid burden was predictive of CBF change in the corresponding vascular territory (Figure 3). Visual reading shows that subjects with high amyloid burden at baseline had a higher increase of CBF at follow‐up (Stable AB+, Figure 4). Conclusion We found that the combination of cardiovascular risk and amyloid burden in AD signature regions was associated with increased CBF in CU individuals, which may reflect a vascular or inflammatory compensatory response to early Alzheimer pathology. Future studies may help understanding how these mechanisms affect cognition.