Purpose The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was developed to evaluate the brain’s glymphatic function or interstitial fluid dynamics. This study aimed to evaluate the reproducibility of the DTI-ALPS method and the effect of modifications in the imaging method and data evaluation. Materials and methods Seven healthy volunteers were enrolled in this study. Image acquisition was performed for this test–retest study using a fixed imaging sequence and modified imaging methods which included the placement of region of interest (ROI), imaging plane, head position, averaging, number of motion-proving gradients, echo time (TE), and a different scanner. The ALPS-index values were evaluated for the change of conditions listed above. Results This test–retest study by a fixed imaging sequence showed very high reproducibility (intraclass coefficient = 0.828) for the ALPS-index value. The bilateral ROI placement showed higher reproducibility. The number of averaging and the difference of the scanner did not influence the ALPS-index values. However, modification of the imaging plane and head position impaired reproducibility, and the number of motion-proving gradients affected the ALPS-index value. The ALPS-index values from 12-axis DTI and 3-axis diffusion-weighted image (DWI) showed good correlation (r = 0.86). Also, a shorter TE resulted in a larger value of the ALPS-index. Conclusion ALPS index was robust under the fixed imaging method even when different scanners were used. ALPS index was influenced by the imaging plane, the number of motion-proving gradient axes, and TE in the imaging sequence. These factors should be uniformed in the planning ALPS method studies. The possibility to develop a 3-axis DWI-ALPS method using three axes of the motion-proving gradient was also suggested.

It has been reported previously that intravenously administered gadolinium-based contrast agent (GBCA) leaks into the subarachnoid space around the cortical veins at 4 h after injection in all old people over 37 years, but not in younger people up to 37 years of age in 3D-real IR images. The purpose of this study was to investigate whether there was a strict threshold of 37 years of age for the leakage of the GBCA into the subarachnoid space. Methods: The subjects included 190 patients, that were scanned for 3D-real IR images at 4 hours after intravenous injection of GBCA as a diagnostic test for endolymphatic hydrops. The patient's age ranged from 14 to 81 years. Two experienced neuroradiologists evaluated the images to determine whether the GBCA leakage around the cortical veins was positive or negative. Any discrepancies between the two observers were discussed and a consensus was obtained. A Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used to compare the positive and the negative group and to set the age cutoff value for the prediction of GBCA leakage. Results: The GBCA leakage around the cortical veins was negative in 35 patients and positive in 155 patients. The average age was 33 ± 11 years in the negative group, and 55 ± 12 years in the positive group (P < 0.01). In the ROC analysis for the age and leakage of the GBCA, an area under the curve was 0.905 and the cutoff age was 37.317 years (sensitivity of 0.942 and specificity of 0.771). Conclusion: Intravenously administered GBCA leaks into the subarachnoid space around the cortical veins in most patients over 37 years of age. However, it should be noted that it can be found occasionally in patients under 37 years of age.

We currently obtain pre-and post-contrast enhanced whole brain 3D-real inversion recovery images for the evaluation of endolymphatic hydrops. We noticed that the space between the pial sheath surrounding the cortical veins and the cortical venous wall is enhanced and this enhancement seems to connect to the meningeal lymphatics along superior sagittal sinus. This new anatomical concept regarding the outflow from the glymphatic system might be important for the future research in neuroscience.

Purpose The purpose of this study was to evaluate the interstitial fluid status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI–ALPS) method, which is a simplified variation of diffusion tensor image analysis along the perivascular space (DTI–ALPS). Materials and methods This retrospective study included data from 128 patients who underwent clinical magnetic resonance imaging (MRI) studies, including DWI, and were found to have no abnormal findings in the brain on MRI. Three motion-probing gradients of the DWI were applied in an orthogonal direction to the imaging plane. Apparent diffusion coefficient images in the x-, y-, and z-axes were retrospectively generated, and composite color images were created to locate the projection and association fiber area on the slice including the body of the lateral ventricle. ALPS indices were calculated, and correlations with age were evaluated using linear and second-degree regression analysis. Linear regression analysis was also performed for a subgroup of patients older than 40 years. In addition, an analysis of variance (ANOVA) test among the generations was performed. Results The linear regression analysis between age and the ALPS index showed a correlation coefficient of −0.20 for all age group and −0.51 for the subgroup older than 40 years. The second-degree regression analysis showed a correlation coefficient of 0.39. ANOVA showed that the 40’s generation showed a statistically significant higher value of ALPS index compared to all other generations except for the 30’s generation. While, the 70’s generation showed a statistically significant lower value of the ALPS index compared to all other generations. Conclusions The analysis of the DWI–APLS method showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40’s generation. This finding in normal subjects may be fundamental in the analysis of disease cases. Secondary abstract We tried to evaluate the glymphatic system status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI–ALPS) method, and the results showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40’s generation.

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