Effects of Arterial Stiffness on Cerebral WM Integrity in Older Adults: A Neurite Orientation Dispersion and Density Imaging and Magnetization Transfer Saturation Imaging Study.

BACKGROUND AND PURPOSE: Arterial stiffness is reported to be able to cause axonal demyelination or degeneration. The present study aimed to use advanced MR imaging techniques to examine the effect of arterial stiffness on the WM microstructure among older adults. MATERIALS AND METHODS: Arterial stiffness was measured using the cardio-ankle vascular elasticity index (CAVI). The high-CAVI (mean CAVI ≥ 9 points) and the low-CAVI groups (mean CAVI < 9 points) were created. The neuronal fiber integrity of the WM was evaluated by neurite orientation dispersion and density imaging and magnetization transfer saturation imaging. Tract-Based Spatial Statistics and the tracts-of-interest analysis were performed. Specific WM regions (corpus callosum, internal capsule, anterior thalamic radiation, corona radiata, superior longitudinal fasciculus, forceps minor, and inferior fronto-occipital fasciculus) were selected in the tracts-of-interest analysis. RESULTS: In Tract-Based Spatial Statistics, the high-CAVI group showed a significantly lower myelin volume fraction value in the broad WM and significantly higher radial diffusivity and isotropic volume fraction values in the corpus callosum, forceps minor, inferior fronto-occipital fasciculus, internal capsule, corona radiata, and anterior thalamic radiation than the low-CAVI group. In tracts-of-interest analysis using multivariate linear regression, significant associations were found between the mean CAVI and radial diffusivity in the anterior thalamic radiation and the corona radiata; isotropic volume fraction in the anterior thalamic radiation and the corona radiata; and myelin volume fraction in the superior longitudinal fasciculus (P < .05). Additionally, partial correlation coefficients were observed for the significant associations of executive function with radial diffusivity and myelin volume fraction (P < .05). CONCLUSIONS: Arterial stiffness could be associated with demyelination rather than axonal degeneration.

An Investigation of Water Diffusivity Changes along the Perivascular Space in Elderly Subjects with Hypertension.

BACKGROUND AND PURPOSE: Hypertension may be related to alterations of the glymphatic system, a waste metabolite drainage system in the brain. We aimed to investigate analysis along the perivascular space index changes in elderly subjects with hypertension. MATERIALS AND METHODS: Diffusion-weighted images were acquired from 126 subjects, including 63 subjects with hypertension (25 men and 38 women; mean age, 72.45 years) and 63 age- and sex-matched controls (25 men and 38 women; mean age, 72.16 years). We calculated the analysis along the perivascular space index as a ratio of the mean of x-axis diffusivities in the projection and association areas to the mean of y-axis diffusivity in the projection area and z-axis diffusivity in the association area. The left, right, and mean analysis along the perivascular space indices of both hemispheres were compared between the hypertension and control groups using a Mann-Whitney U test. The Spearman correlation coefficient was used to assess the correlation between the left, right, and mean ALPS indices and blood pressure and pulse pressure. RESULTS: The left (P = .011) and mean (P = .024) analysis along the perivascular space indices of the hypertension group were significantly lower than that of the control group. The left, right, and mean analysis along the perivascular space indices of all subjects were significantly negatively correlated with blood pressure values (r = -0.200 to -0.278, P = .002-0.046) and pulse pressure values (r = -0.221 to -0.245, P = .006-0.013). CONCLUSIONS: Our results are consistent with a model in which hypertension causes glymphatic dysfunction.

3D Quantitative Synthetic MRI in the Evaluation of Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: Synthetic MR imaging creates multiple contrast-weighted images based on a single time-efficient quantitative scan, which has been mostly performed for 2D acquisition. We assessed the utility of 3D synthetic MR imaging in patients with MS by comparing its diagnostic image quality and lesion volumetry with conventional MR imaging. MATERIALS AND METHODS: Twenty-four patients with MS prospectively underwent 3D quantitative synthetic MR imaging and conventional T1-weighted, T2-weighted, FLAIR, and double inversion recovery imaging, with acquisition times of 9 minutes 3 seconds and 18 minutes 27 seconds for the synthetic MR imaging and conventional MR imaging sequences, respectively. Synthetic phase-sensitive inversion recovery images and those corresponding to conventional MR imaging contrasts were created for synthetic MR imaging. Two neuroradiologists independently assessed the image quality on a 5-point Likert scale. The numbers of cortical lesions and lesion volumes were quantified using both synthetic and conventional image sets. RESULTS: The overall diagnostic image quality of synthetic T1WI and double inversion recovery images was noninferior to that of conventional images (P = .23 and .20, respectively), whereas that of synthetic T2WI and FLAIR was inferior to that of conventional images (both Ps < .001). There were no significant differences in the number of cortical lesions (P = .17 and .53 for each rater) or segmented lesion volumes (P = .61) between the synthetic and conventional image sets. CONCLUSIONS: Three-dimensional synthetic MR imaging could serve as an alternative to conventional MR imaging in evaluating MS with a reduced scan time.

White Matter Abnormalities in Multiple Sclerosis Evaluated by Quantitative Synthetic MRI, Diffusion Tensor Imaging, and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND AND PURPOSE: A number of MR-derived quantitative metrics have been suggested to assess the pathophysiology of MS, but the reports about combined analyses of these metrics are scarce. Our aim was to assess the spatial distribution of parameters for white matter myelin and axon integrity in patients with relapsing-remitting MS by multiparametric MR imaging. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting MS and 24 age- and sex-matched controls were prospectively scanned by quantitative synthetic and 2-shell diffusion MR imaging. Synthetic MR imaging data were used to retrieve relaxometry parameters (R1 and R2 relaxation rates and proton density) and myelin volume fraction. Diffusion tensor metrics (fractional anisotropy and mean, axial, and radial diffusivity) and neurite orientation and dispersion index metrics (intracellular volume fraction, isotropic volume fraction, and orientation dispersion index) were retrieved from diffusion MR imaging data. These data were analyzed using Tract-Based Spatial Statistics. RESULTS: Patients with MS showed significantly lower fractional anisotropy and myelin volume fraction and higher isotropic volume fraction in widespread white matter areas. Areas with different isotropic volume fractions were included within areas with lower fractional anisotropy. Myelin volume fraction showed no significant difference in some areas with significantly decreased fractional anisotropy in MS, including in the genu of the corpus callosum and bilateral anterior corona radiata, whereas myelin volume fraction was significantly decreased in some areas where fractional anisotropy showed no significant difference, including the bilateral posterior limb of the internal capsule, external capsule, sagittal striatum, fornix, and uncinate fasciculus. CONCLUSIONS: We found differences in spatial distribution of abnormality in fractional anisotropy, isotropic volume fraction, and myelin volume fraction distribution in MS, which might be useful for characterizing white matter in patients with MS.

Neuromelanin or DaT-SPECT: which is the better marker for discriminating advanced Parkinson's disease?

BACKGROUND AND PURPOSE: Whether the neuromelanin-positive substantia nigra pars compacta area (NM-SNc) on neuromelanin magnetic resonance imaging (NM-MRI) and the specific binding ratio (SBR) on 123 I-N-v-fluoropropyl-2b-carbomethoxy3b-(4-iodophenyl)nortropane single photon emission computed tomography (DaT-SPECT) can be correlated with motor fluctuations (MFs) in advanced Parkinson's disease (PD) was investigated. METHODS: Thirty-five PD patients (60 ± 13 years) and 23 healthy individuals as controls (59 ± 19 years) were enrolled. The relationships between NM-MRI and DaT-SPECT were prospectively examined in two subgroups divided according to the presence or absence of MFs. Multivariate analysis was performed using the Cox proportional hazard model to screen for association factors. RESULTS: The NM-SNc size was correlated with the SBR (Spearman's ρ = 0.43, P < 0.05). The NM-SNc size was significantly reduced in PD with MFs compared with the subgroup without (P < 0.001), whereas the SBR did not significantly differ between the groups. NM-SNc size was a significant association factor for MFs (hazard ratio 0.94, P = 0.04). In receiver operating characteristic analysis of the factors for MF occurrence, the area under the receiver operating characteristic curve of the NM-SNc size showed a significant difference of 0.89 (P < 0.05) but no significant difference was found in the SBR. CONCLUSIONS: NM-SNc size was significantly correlated with the SBR in PD, but several factors in advanced PD were more closely associated with NM-SNc size than the SBR. NM-MRI might reflect the status of advanced PD more accurately than DaT-SPECT. Therefore, NM-MRI appears to provide a better marker for discriminating advanced PD than DaT-SPECT.

Improving the Quality of Synthetic FLAIR Images with Deep Learning Using a Conditional Generative Adversarial Network for Pixel-by-Pixel Image Translation.

BACKGROUND AND PURPOSE: Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through conditional generative adversarial network training. MATERIALS AND METHODS: Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed. RESULTS: The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all P < .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (P = 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (P = .003) and swelling artifacts (in all cases) than synthetic FLAIR images. CONCLUSIONS: Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.

Effect of Gadolinium on the Estimation of Myelin and Brain Tissue Volumes Based on Quantitative Synthetic MRI.

BACKGROUND AND PURPOSE: The effect of gadolinium on the estimation of myelin has not been reported. The aim of the current study was to investigate the effects of gadolinium on automatic myelin and brain tissue volumetry via quantitative synthetic MR imaging. MATERIALS AND METHODS: The study included 36 patients who were referred for brain metastases screening, and quantitative synthetic MR imaging data before and after gadolinium-based contrast agent administration were analyzed retrospectively. Brain metastases were detected in 17 patients. WM volume, GM volume, CSF volume, non-WM/GM/CSF volume, myelin volume, brain parenchymal volume, myelin fraction (myelin volume/brain parenchymal volume), and intracranial volume were estimated. T1 and T2 relaxation times, proton density, and myelin partial volume per voxel averaged across the brain parenchyma were also analyzed. RESULTS: In patients with and without metastases after gadolinium-based contrast agent administration, measurements of WM and myelin volumes, and myelin fraction were significantly increased (+26.65 and +29.42 mL, +10.14 and +12.46 mL, +0.88% and +1.09%, respectively), whereas measurements of GM, CSF, brain parenchymal, and intracranial volumes were significantly decreased (-36.23 and -34.49 mL, -20.77 and -18.94 mL, -6.76 and -2.84 mL, -27.41 and -21.84 mL, respectively). Non-WM/GM/CSF volume did not show a significant change. T1, T2, and proton density were significantly decreased (-51.34 and -46.84 ms, -2.67 and -4.70 ms, -1.05%, and -1.28%, respectively) after gadolinium-based contrast agent administration, whereas measurements of myelin partial volume were significantly increased (+0.78% and +0.75%, respectively). CONCLUSIONS: Gadolinium had a significant effect on the automatic calculation of myelin and brain tissue volumes using quantitative synthetic MR imaging, which can be explained by decreases in T1, T2, and proton density.

Automated brain tissue and myelin volumetry based on quantitative MR imaging with various in-plane resolutions.

BACKGROUND AND PURPOSE: Segmented brain tissue and myelin volumes can now be automatically calculated using dedicated software (SyMRI), which is based on quantification of R1 and R2 relaxation rates and proton density. The aim of this study was to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions. METHODS: We scanned 10 healthy subjects on a 1.5T MR scanner with in-plane resolutions of 0.8, 2.0 and 3.0mm. Two scans were performed for each resolution. The acquisition time was 7-min and 24-sec for 0.8mm, 3-min and 9-sec for 2.0mm and 1-min and 56-sec for 3.0mm resolutions. The volumes of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV) and myelin were compared between in-plane resolutions. Repeatability for each resolution was then analyzed. RESULTS: No significant differences in volumes measured were found between the different in-plane resolutions, except for NoN between 0.8mm and 2.0mm and between 2.0mm and 3.0mm. The repeatability error value for the WM, GM, CSF, NoN, BPV and myelin volumes relative to ICV was 0.97%, 1.01%, 0.65%, 0.86%, 1.06% and 0.25% in 0.8mm; 1.22%, 1.36%, 0.73%, 0.37%, 1.18% and 0.35% in 2.0mm and 1.18%, 1.02%, 0.96%, 0.45%, 1.36%, and 0.28% in 3.0mm resolutions. CONCLUSION: SyMRI brain tissue and myelin volumetry with low in-plane resolution and short acquisition times is robust and has a good repeatability so could be useful for follow-up studies.

Synthetic MRI in the Detection of Multiple Sclerosis Plaques.

BACKGROUND AND PURPOSE: Synthetic MR imaging enables the creation of various contrast-weighted images including double inversion recovery and phase-sensitive inversion recovery from a single MR imaging quantification scan. Here, we assessed whether synthetic MR imaging is suitable for detecting MS plaques. MATERIALS AND METHODS: Quantitative and conventional MR imaging data on 12 patients with MS were retrospectively analyzed. Synthetic T2-weighted, FLAIR, double inversion recovery, and phase-sensitive inversion recovery images were produced after quantification of T1 and T2 values and proton density. Double inversion recovery images were optimized for each patient by adjusting the TI. The number of visible plaques was determined by a radiologist for a set of these 4 types of synthetic MR images and a set of conventional T1-weighted inversion recovery, T2-weighted, and FLAIR images. Conventional 3D double inversion recovery and other available images were used as the criterion standard. The total acquisition time of synthetic MR imaging was 7 minutes 12 seconds and that of conventional MR imaging was 6 minutes 29 seconds The lesion-to-WM contrast and lesion-to-WM contrast-to-noise ratio were calculated and compared between synthetic and conventional double inversion recovery images. RESULTS: The total plaques detected by synthetic and conventional MR images were 157 and 139, respectively (P = .014). The lesion-to-WM contrast and contrast-to-noise ratio on synthetic double inversion recovery images were superior to those on conventional double inversion recovery images (P = .001 and < 0.001, respectively). CONCLUSIONS: Synthetic MR imaging enabled detection of more MS plaques than conventional MR imaging in a comparable acquisition time. The contrast for MS plaques on synthetic double inversion recovery images was better than on conventional double inversion recovery images.

Usefulness of Non-Contrast-Enhanced MR Angiography Using a Silent Scan for Follow-Up after Y-Configuration Stent-Assisted Coil Embolization for Basilar Tip Aneurysms.

BACKGROUND AND PURPOSE: Y-configuration stent-assisted coil embolization is used for treating wide-neck aneurysms. Noninvasive alternatives to x-ray DSA for follow-up after Y-configuration stent-assisted coil embolization treatment are required. This study aimed to assess the usefulness of non-contrast-enhanced MRA by using a Silent Scan (silent MRA) for follow-up after Y-configuration stent-assisted coil embolization for basilar tip aneurysms. MATERIALS AND METHODS: Seven patients treated with Y-configuration stent-assisted coil embolization for basilar tip aneurysms underwent silent MRA, 3D TOF-MRA, and DSA. Silent MRA and 3D TOF-MRA images were obtained during the same scan session on a 3T MR imaging system. Two neuroradiologists independently reviewed both types of MRA images and subjectively scored the flow in the stents on a scale of 1 (not visible) to 5 (nearly equal to DSA) by referring to the latest DSA image as a criterion standard. Furthermore, we evaluated the visualization of the neck remnant. RESULTS: In all patients, the 2 observers gave a higher score for the flow in the stents on silent MRA than on 3D TOF-MRA. The average score ± standard deviation was 4.07 ± 0.70 for silent MRA and 1.93 ± 0.80 (P < .05) for 3D TOF-MRA. Neck remnants were depicted by DSA in 5 patients. In silent MRA, neck remnants were depicted in 5 patients, and visualization was similar to DSA; however, in 3D TOF-MRA, neck remnants were depicted in only 1 patient. CONCLUSIONS: Silent MRA might be useful for follow-up after Y-configuration stent-assisted coil embolization.

Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to examine the osteoarthritis (OA)-related structural changes associated with histological synovitis in end-stage knee OA patients. METHODS: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 y) were enrolled. All participants underwent 3.0-T MRI. The structural changes, such as cartilage morphology, subchondral bone marrow lesion (BML), subchondral bone cyst (SBC), subchondral bone attrition (SBA), osteophytes, meniscal lesion and synovitis, were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest (ROIs) of the knee joint during total joint replacement surgery. The associations between the histological synovitis score (HSS) and WORMS or the synovial expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6 and transforming growth factor (TGF)-ß were examined using Spearman's correlation coefficient. RESULTS: Among the seven OA-related structural changes, the BML, SBC, SBA and synovitis were significantly associated with the HSS (r = 0.33, 0.35, 0.48 and 0.36, respectively), while other morphological changes were not. Although synovial COX-2, IL-1ß or IL-6 expression levels were not associated with the HSS, the synovial TGF-ß expression levels were associated with the HSS. CONCLUSION: The presence of BML, SBC and SBA was associated with histological synovitis in end-stage knee OA patients.

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent-Assisted Coil Embolization for Anterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation. MATERIALS AND METHODS: Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard. RESULTS: Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001). CONCLUSIONS: Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

White matter alteration of the cingulum in Parkinson disease with and without dementia: evaluation by diffusion tensor tract-specific analysis.

BACKGROUND AND PURPOSE: In PD, the neurodegenerative process begins in the brain stem and extends to the limbic system and finally into the cerebral cortex. We used diffusion tensor tractography to investigate the FA of the cingulate fiber tracts in patients with PD with and without dementia. MATERIALS AND METHODS: Fifteen patients with PD, 15 patients with PDD, and 15 age-matched healthy controls underwent diffusion tensor imaging with a 3T MR imager. Diffusion tensor tractography images of the anterior and posterior cingulate fiber tracts were generated. Mean diffusivity and FA were measured along the tractography of the anterior and posterior cingulate fiber tracts. One-way ANOVA with the Scheffé post hoc test was used to compare results among the groups. RESULTS: FA was significantly lower in patients with PDD than in healthy controls in both the anterior and the posterior cingulate fiber tracts (P = .003, P = .015) and significantly lower in patients with PD than in healthy controls (P = .003) in the anterior cingulate fiber tract. There were no significant mean diffusivity differences among the groups. MMSE and FA values of the anterior cingulate fiber tracts in patients with PDD were significantly correlated (r = 0.633, P < .05). CONCLUSIONS: The reduced FA in patients with PD and PDD might reflect neuropathologic changes such as Lewy body pathology in the cingulate fibers. This abnormality might contribute to the dementing process in PD.

Two KaiA-binding domains of cyanobacterial circadian clock protein KaiC.

kaiABC, a gene cluster, encodes KaiA, KaiB and KaiC proteins that are essential to circadian rhythms in the unicellular cyanobacterium Synechococcus sp. strain PCC 7942. Kai proteins can interact with each other in all possible combinations. This study identified two KaiA-binding domains (C(KABD1) and C(KABD2)) in KaiC at corresponding regions of its duplicated structure. Clock mutations on the two domains and kaiA altered the strength of C(KABD)-KaiA interactions assayed by the yeast two-hybrid system. Thus, interaction between KaiA and KaiC through C(KABD1) and C(KABD2) is likely important for circadian timing in the cyanobacterium.

A selective inhibitor of intestinal ACAT, EAB309 suppresses both intestinal and hepatic cholesterol output and stimulates chylomicron removal.

The effect of a novel inhibitor of acylcoenzyme A:cholesterol acyltransferase (EC 2.3.1.26, ACAT), EAB309 (EAB) on plasma lipid metabolism was studied in cholesterol-fed rats. Orally administered EAB was not detected in the portal vein or the liver but distributed exclusively in the intestine, suggesting that this agent selectively inhibits intestinal ACAT. The rats were fed with either a cholesterol-diet or a cholesterol-diet containing 0.005% EAB (w/w) ad. libium for three weeks. ACAT activity in intestinal microsomes was significantly inhibited in EAB-treated rats. Hepatic ACAT activity was also decreased in EAB-treated rats, however, this was attenuated by the addition of excess cholesterol to the liver microsome, indicating that substrate availability is tightly associated with this enzyme's activity and the inhibition of hepatic ACAT by EAB is not direct. Incorporation of [3H]-cholesterol to cholesteryl ester (CE) in mesenteric lymph were markedly suppressed by EAB treatment. Chylomicrons (CMs) were doubly labeled with [3H]-vitamin A and [14C]-triglyceride (TG) in EAB-treated or non-treated rats and injected into normal chow-fed rats. The CMs from EAB-treated rats were cleared faster from the plasma and taken up more by the liver compared with the CMs from non-treated rats. The content of CE in newly secreted VLDL was remarkably decreased by EAB treatment without affecting TG output. These results demonstrate that EAB, a novel inhibitor of intestinal ACAT, significantly suppresses both intestinal and hepatic CE output and stimulates CM removal. This suggests that the inhibition of intestinal ACAT can subsequently suppress hepatic ACAT by decreased CE delivery from the intestine to the liver.