Repeatability and Reproducibility of pseudo-Continuous Arterial Spin Labeling Measured Brain Perfusion in Healthy Volunteers and Glioblastoma Patients.

Background and purpose: Arterial spin labeled (ASL) MRI has gained recognition as a quantitative perfusion imaging method for managing patients with brain tumors. Limited studies have so far investigated the reproducibility of ASL-derived perfusion in patients with brain tumors. This study aims to evaluate intrasession repeatability and intersession reproducibility of perfusion measurements using 3D pseudo-continuous ASL (pCASL) with Cartesian TSE (TSE-CASPR) in healthy volunteers (HV) and glioblastoma (GBM) patients at 3 Tesla and compare against 3D pCASL with GRASE.

Materials and methods: This prospective study (NCT03922984) was approved by the institutional review board and written informed consent was obtained from all subjects. HV underwent repeated pCASL evaluations 2-4 weeks apart between November 2021 and October 2022. GBM patients were recruited for longitudinal MRI from September 2019 to February 2023. Intrasession repeatability (HV and GBM) and intersession reproducibility (HV only) of pCASL were assessed using linear regression, Bland-Altman analyses, intraclass correlation coefficient (ICC) with 95% confidence interval (CI), and within-subject coefficients of variation (wsCV).

Results: Twenty HV (9 men, age: 25.1±1.7 years, range 23-30 years) and 21 GBM patients (15 men; age: 59.8±14.3 years, range 28-81 years) were enrolled. Within imaging session, 3D pCASL measured perfusion with TSE-CASPR and GRASE respectively achieved high R² values (0.88-0.95; 0.93-0.96), minimal biases (-0.46 to 0.81; -0.08 to 0.35 mL/100g/min), high ICC [95% CI] (0.96-0.98 [0.94-0.98]; 0.96-0.98 [0.92-0.99]), and low wsCV (6.64%-9.07%; 5.20%-8.16%) in HV (N=20) and GBM patients (N=21). Across imaging session, 3D pCASL in HV (N=20) achieved high R² values (0.71; 0.82), minimal biases (-1.2; -0.90 mL/100g/min), high ICC [95% CI] values (0.85 [0.81-0.89]; 0.90 [0.87-0.93]), and low wsCV values (13.82%; 9.98%).

Conclusions: Our study demonstrated excellent intrasession repeatability of 3D pCASL measured cerebral perfusion in HV and GBM patients and good to excellent intersession reproducibility in HV. 3D pCASL with GRASE performed slightly better than 3D pCASL with TSE-CASPR in HV; however, in GBM patients, 3D pCASL with TSE-CASPR showed better performance in tumor regions with nearly twofold higher SNR. ASL measured perfusion could serve as a non-contrast quantitative imaging biomarker to facilitate the management of GBM patients.

Abbreviations: ASL = arterial spin labeling; pCASL = pseudo-continuous arterial spin labeling; GBM = glioblastoma; CBF = cerebral blood flow; CASPR = Cartesian acquisition with spiral profile reordering; GRASE = gradient and spin echo; NAGM = normal-appearing gray matter.