Background
17O‐labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow.
Purpose
To evaluate the safety and feasibility of PSO17.
Study Type
Prospective study.
Subjects
A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (normal saline), PSO17 10%, and PSO17 20%.
Field Strength/Sequence
Dynamic 3D fluid attenuated inversion recovery (FLAIR, fast spin echo with variable refocusing flip angle) scans of the brain were performed with 3‐T MRI.
Assessment
Contrast agents were injected 5 minutes after the start of a 10‐minute scan. Any symptoms, vital signs, and blood and urine tests were evaluated at five timepoints from preinjection to 4 days after. Blood samples for pharmacokinetic analysis, including half‐life (T1/2), maximum fraction (Cmax), time‐to‐maximum fraction (Tmax), and area under the curve (AUC), were collected at 13 timepoints from preinjection to 168 hours after. Regions of interest were set in the cerebral cortex (CC), basal ganglia/thalamus (BG/TM), and white matter (WM), and 17O concentrations were calculated from signal changes and evaluated using Cmax.
Statistical Tests
All items were compared among the three groups using Tukey–Kramer's honestly significant difference test. Statistical significance was defined as P < 0.5.
Results
No safety issues were noted with the intravenous administration of PSO17. The T1/2 was approximately 160 hours, and the AUCs were 1.77 ± 0.10 and 3.75 ± 0.36 in the PSO17 10% and 20% groups, respectively. 17O fractions calculated from MRI signals were higher in the PSO17 20% group than in the 10% and placebo groups. Significant differences were noted between all pairs of groups in the CC and BG/TM, and between PSO17 20% and both placebo and 10% groups in the WM.
Data Conclusion
PSO17 might be considered safe as a contrast medium. Dynamic 3D‐FLAIR might detect dose‐dependent signal changes and estimate 17O.
Evidence Level
1
Technical Efficacy
Stage 1
Quantitative susceptibility mapping (QSM) is a new magnetic resonance imaging (MRI) technique for noninvasively estimating the magnetic susceptibility of biological tissue. Several methods for QSM have been proposed. One of these methods can estimate susceptibility with high accuracy in tissues whose contrast is consistent between magnitude images and susceptibility maps, such as deep gray-matter nuclei. However, the susceptibility of small veins is underestimated and not well depicted by using the above approach, because the contrast of small veins is inconsistent between a magnitude image and a susceptibility map. In order to improve the estimation accuracy and visibility of small veins without streaking artifacts, a method with multiple dipole-inversion combination with k-space segmentation (MUDICK) has been proposed. In the proposed method, k-space was divided into three domains (low-frequency, magic-angle, and high-frequency). The k-space data in low-frequency and magic-angle domains were obtained by L1-norm regularization using structural information of a pre-estimated susceptibility map. The k-space data in high-frequency domain were obtained from the pre-estimated susceptibility map in order to preserve small-vein contrasts. Using numerical simulation and human brain study at 3 Tesla, streaking artifacts and small-vein susceptibility were compared between MUDICK and conventional methods (MEDI and TKD). The numerical simulation and human brain study showed that MUDICK and MEDI had no severe streaking artifacts and MUDICK showed higher contrast and accuracy of susceptibility in small-veins compared to MEDI. These results suggest that MUDICK can improve the accuracy and visibility of susceptibility in small-veins without severe streaking artifacts.
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