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More than 5 years have passed since the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) method was proposed with the intention of evaluating the glymphatic system. This method is handy due to its noninvasiveness, provision of a simple index in a straightforward formula, and the possibility of retrospective analysis. Therefore, the ALPS method was adopted to evaluate the glymphatic system for many disorders in many studies. The purpose of this review is to look back and discuss the ALPS method at this moment.The ALPS-index was found to be an indicator of a number of conditions related to the glymphatic system. Thus, although this was expected in the original report, the results of the ALPS method are often interpreted as uniquely corresponding to the function of the glymphatic system. However, a number of subsequent studies have pointed out the problems on the data interpretation. As they rightly point out, a higher ALPS-index indicates predominant Brownian motion of water molecules in the radial direction at the lateral ventricular body level, no more and no less. Fortunately, the term "ALPS-index" has become common and is now known as a common term by many researchers. Therefore, the ALPS-index should simply be expressed as high or low, and whether it reflects a glymphatic system is better to be discussed carefully. In other words, when a decreased ALPS-index is observed, it should be expressed as "decreased ALPS-index" and not directly as "glymphatic dysfunction". Recently, various methods have been proposed to evaluate the glymphatic system. It has become clear that these methods also do not seem to reflect the entirety of the extremely complex glymphatic system. This means that it would be desirable to use various methods in combination to evaluate the glymphatic system in a comprehensive manner.

Interest in interstitial fluid dynamics has increased since the proposal of the glymphatic system hypothesis. Abnormal dynamics of the interstitial fluid have been pointed out to be an important factor in various pathological statuses. In this article, we propose the concept of central nervous system interstitial fluidopathy as a disease or condition in which abnormal interstitial fluid dynamics is one of the important factors for the development of a pathological condition. We discuss the aspects of interstitial fluidopathy in various diseases, including Alzheimer's disease, Parkinson's disease, normal pressure hydrocephalus, and cerebral small vessel disease. We also discuss a method called "diffusion tensor image analysis along the perivascular space" using MR diffusion images, which is used to evaluate the degree of interstitial fluidopathy or the activity of the glymphatic system.

Purpose: Decrease in signal of the cerebrospinal fluid (CSF) on low b-value diffusion weighted image (DWI) due to non-uniform flow can provide additional information regarding CSF motion. The purpose of the current study was to evaluate whether arterial pulsations constitute the driving force of CSF motion., Methods: We evaluated the CSF signals within the Sylvian fissure on low b-value DWI in 19 patients with unilateral middle cerebral artery (MCA) occlusion. DWI with b-value of 500 s/mm 2 was evaluated for a decrease in CSF signal within the Sylvian fissure including the Sylvian vallecula and lower, middle, and higher Sylvian fissures and graded as follows: the same as contralateral side; smaller signal decrease than that on contralateral side; and no signal decrease. MR angiography (MRA) findings of MCA were graded as follows: the same as contralateral, lower signal than contralateral signal, and no signal. In 15 patients, regional cerebral blood flow (rCBF) was evaluated using single-photon emission computed tomography (SPECT) studies and graded as >90%, 90%-70%, and <70% rCBF compared to contralateral. The correlations between the gradings were evaluated using G likelihood-ratio test., Results: There was no statistically significant correlation between the MRA and low b-value DWI gradings of CSF in all areas. There were statistically significant correlations between the decreases in CBF on SPECT and CSF signals in the middle Sylvian fissure., Conclusion: The driving force of CSF pulsation in the Sylvian sinus may be related to the pulsations of the cerebral hemisphere rather than direct arterial pulsations.

Purpose: To investigate the association between signal changes over time in perivenous cystic structures near the superior sagittal sinus and leakage of a gadolinium-based contrast agent (GBCA) into the subarachnoid space in patients with suspected endolymphatic hydrops., Methods: Fifty-one cystic structures in 27 cases were evaluated. The signal intensity of the cystic structures was measured on 3D real inversion recovery (3D-real IR) images obtained at pre-, and at 10 min, 4 hrs and 24 hrs post-intravenous administration (IV) of GBCA. Signal enhancement of the cystic structures from the pre-contrast images at each time point was compared in subjects with leakage (positive) versus those without leakage (negative) using an ANOVA. Fisher's exact probability test was used to compare the maximum contrast-enhanced time point between positive and negative groups. We used 5% as a threshold to determine statistical significance., Results: In leakage positive subjects, mean signal enhancement of the cysts was significantly greater at 4 and 24 hrs compared to 10 min. However, although there was a trend of an increase from 4 to 24 hrs, the difference was not significant. In the leakage negative group, mean signal enhancement of the cysts was significantly higher at 4 hrs compared to 10 min and 24 hrs. There was no significant difference between 10 min and 24 hrs. In the positive group, the maximum signal increase was found in 10/38 and 28/38 cysts at 4 and 24 hrs after IV-GBCA, respectively. In the leakage negative group, the maximum signal increase was found in 10/13 and 3/13 cysts at 4 and 24 hrs, respectively (P = 0.0019)., Conclusion: There was an association between signal changes over time after IV-GBCA in perivenous cystic structures and leakage of GBCA. Further research to clarify the impact of cystic structures on the function of the waste clearance system of the brain is warranted.

Purpose: The purpose of this retrospective study was to investigate the relationship between the number and size of cystic structures around the cortical veins near the superior sagittal sinus and the leakage of gadolinium-based contrast agent (GBCA) around the cortical veins., Methods: Of 190 patients (91 male and 99 female), that were scanned at 4 h after an intravenous injection of GBCA as a diagnostic examination for endolymphatic hydrops, 6 patients with GBCA leakage were younger than the previously proposed threshold age of 37.3 years for leakage. Six age-matched patients without leakage were also included for reference. In addition, we included 8 cases without leakage that were older than the hypothesized threshold of 37.3 years, as well as 8 age-matched patients with GBCA leakage into the cerebrospinal fluid space. The number of cysts was counted and the sizes were measured in these 28 patients (age: 32-60 years old, 13 men and 15 women)., Results: The mean number of cysts surrounding the cortical veins in the parasagittal region was 4.29 ± 1.77 vs. 1.79 ± 1.05 (P = 0.0001) in the subjects with and without GBCA leakage, respectively. The mean size of the largest cysts was at 8.89 ± 3.49 mm vs. 5.69 ± 2.29 (P = 0.009) in the subjects with and without GBCA leakage, respectively., Conclusion: The number and size of the perivenous cystic structures near the superior sagittal sinus is greater in subjects with GBCA leakage into the subarachnoid space compared with those without leakage. Future research regarding the histological and functional details of these parasagittal cystic structures is needed.

Purpose: MRI of endolymphatic hydrops (EH) 4 h after intravenous administration of a single dose of gadolinium-based contrast agent is used for clinical examination in some institutions; however, further improvement in image quality would be valuable for wider clinical utility. Denoising using deep learning reconstruction (Advanced Intelligent Clear-IQ Engine [AiCE]) has been reported for CT and MR. The purpose of this study was to compare the contrast-to-noise ratio of endolymph to perilymph (CNR EP ) between the improved hybrid of reversed image of the positive endolymph signal and the native image of the perilymph signal multiplied with the heavily T 2 -weighted MR cisternography (iHYDROPS-Mi2) images, which used AiCE for the three source images (i.e. positive endolymph image [PEI], positive perilymph image [PPI], MR cisternography [MRC]) to those that did not use AiCE. We also examined if there was a difference between iHYDROPS-Mi2 images with and without AiCE for degree of visual grading of EH and in endolymphatic area [EL] ratios., Methods: Nine patients with suspicion of EH were imaged on a 3T MR scanner. iHYDROPS images were generated by subtraction of PEI images from PPI images. iHYDROPS-Mi2 images were then generated by multiplying MRC with iHYDROPS images. The CNR EP and EL ratio were measured on the iHYDROPS-Mi2 images. Degree of radiologist visual grading for EH was evaluated., Results: Mean CNR EP ± standard deviation was 1681.8 ± 845.2 without AiCE and 7738.6 ± 5149.2 with AiCE (P = 0.00002). There was no significant difference in EL ratio for images with and without AiCE. Radiologist grading for EH agreed completely between the 2 image types in both the cochlea and vestibule., Conclusion: The CNR EP of iHYDROPS-Mi2 images with AiCE had more than a fourfold increase compared with that without AiCE. Use of AiCE did not adversely affect radiologist grading of EH.

Purpose: We explored normal diameter values of the cochlear (CN) and facial (FN) nerves on 3-dimensional constructive interference in steady state (3D-CISS) using a 3-tesla magnetic resonance (MR) imaging scanner., Methods: A total of 142 patients underwent MR imaging of the inner ear at 3T. We retrospectively analyzed data from 172 ears. All ears had normal hearing and no history of ipsilateral facial palsy. Parasagittal images of 0.5-mm thickness perpendicular to the internal auditory canal were reconstructed from 0.4-mm thick axial 3D-CISS images for all ears. Two independent radiologists measured the long diameter (LD), short diameter (SD), and cross-sectional area (CSA) of each CN and FN. For each measurement, we calculated the mean value from the 2 observers and evaluated interobserver agreement. We also evaluated the correlation between nerve diameter and sex and age., Results: Both observers could perform measurements in 157 CN from 172 ears (91%) and 165 FN from 172 ears (96%). For the CN, the mean LD was 1.35±0.16 mm, the mean SD was 0.99±0.18 mm, and the mean CSA was 1.07±0.30 mm2; for the FN, the mean values were 1.18±0.17 mm (LD), 0.87±0.16 mm (SD), and 0.83±0.27 mm2 (CSA). Interobserver reliability was good for each measurement (r=0.569 to 0.691, P<0.01). The diameters of the 2 nerves tended to be larger in men, but only the CSA of the FN was significantly larger in men (P<0.05). Age did not affect nerve diameter., Conclusion: We present normal values of CN and FN diameters on 3D-CISS at 3T. Our results warrant further study to clarify the pathophysiological state of the CN or FN using 3D-CISS.

Purpose: Many inner ear disorders, including Ménière's disease, are believed to be based on endolymphatic hydrops. We evaluated a newly proposed method for semi-quantification of endolymphatic size in patients with suspected endolymphatic hydrops that uses 2 kinds of processed magnetic resonance (MR) images., Methods: Twenty-four consecutive patients underwent heavily T2-weighted (hT2W) MR cisternography (MRC), hT2W 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) with inversion time of 2250 ms (positive perilymph image, PPI), and hT2W-3D-IR with inversion time of 2050 ms (positive endolymph image, PEI) 4 hours after intravenous administration of single-dose gadolinium-based contrast material (IV-SD-GBCM). Two images were generated using 2 new methods to process PPI, PEI, and MRC. Three radiologists contoured the cochlea and vestibule on MRC, copied regions of interest (ROIs) onto the 2 kinds of generated images, and semi-quantitatively measured the size of the endolymph for the cochlea and vestibule by setting a threshold pixel value., Results: Each observer noted a strong linear correlation between endolymphatic size of both the cochlea and vestibule of the 2 kinds of generated images. The Pearson correlation coefficients (r) were 0.783, 0.734, and 0.800 in the cochlea and 0.924, 0.930, and 0.933 in the vestibule (P<0.001, for all). In both the cochlea and vestibule, repeated-measures analysis of variance showed no statistically significant difference between observers., Conclusion: Use of the 2 kinds of generated images generated from MR images obtained 4 hours after IV-SD-GBCM might enable semi-quantification of endolymphatic size with little observer dependency.