Myelin heterogeneity for assessing normal appearing white matter myelin damage in multiple sclerosis.

BACKGROUND AND PURPOSE: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin. Mean MWF reflects average myelin content, while MWF standard deviation (SD) describes variation in myelin within regions. The myelin heterogeneity index (MHI = SD/mean MWF) is a composite metric of myelin content and myelin variability. We investigated how mean MWF, SD, and MHI compare in differentiating MS from controls and their associations with physical and cognitive disability. METHODS: Myelin water imaging data were acquired from 91 MS participants and 31 healthy controls (HC). Segmented whole-brain NAWM and corpus callosum (CC) NAWM, mean MWF, SD, and MHI were compared between groups. Associations of mean MWF, SD, and MHI with Expanded Disability Status Scale and Symbol Digit Modalities Test were assessed. RESULTS: NAWM and CC MHI had the highest area under the curve: .78 (95% confidence interval [CI]: .69, .86) and .84 (95% CI: .76, .91), respectively, distinguishing MS from HC. CONCLUSIONS: Mean MWF, SD, and MHI provide complementary information when assessing regional and global NAWM abnormalities in MS and associations with clinical outcome measures. Examining all three metrics (mean MWF, SD, and MHI) enables a more detailed interpretation of results, depending on whether regions of interest include areas that are more heterogeneous, earlier in the demyelination process, or uniformly injured.

Dimensional Changes of Yttria-stabilized Zirconia under Different Preparation Designs and Sintering Protocols.

PURPOSE: To evaluate the linear and volumetric dimensional changes that occur throughout the fabrication process of monolithic 4.5-6% yttria-stabilized zirconia copings under the influence of different preparation designs and two sintering protocols. MATERIALS AND METHODS: A titanium master die was fabricated using Atlantis core file implant-abutment. Six copings were designed virtually according to different finish line offsets and coping thicknesses, with four equidistant occlusal posts for linear measurements. Zirconia copings were milled using IPS e.max ZirCAD LT zirconia blanks. The experimental groups according to the coping designs were the following: G1: 0.5 mm finish line offset, 0.5 mm thickness; G2: 0.5 mm finish line offset, 1.0 mm thickness; G3: 0.5 mm finish line offset, 1.5 mm thickness; G4: 1.2 mm finish line offset, 0.5 mm thickness; G5: 1.2 mm finish line offset, 1.0 mm thickness; G6: 1.2 mm finish line offset, 1.5 mm thickness. Six samples per group were sintered by standard sintering (SS) and the other six by fast sintering (FS). Linear and volumetric measurements were taken at the three fabrication stages (virtual design, milling stage, and sintering) by using an intraoral scanner and imported as the .stl file to Meshmixer software for analysis. Statistical analysis was performed by a linear mixed effect model via statistical software R (R Core team, 2018). RESULTS: There was a significant interaction between the coping design group, stage of fabrication and sintering protocol on the linear (F = 4.451, p < 0.001) and volumetric (F = 2.716; p < 0.001) dimensional changes. Standard sintering G1 showed the smallest linear and dimensional changes among the groups compared to the reference design. Sintered copings had shrunk on average 1.32% within SS and 1.54% within FS linearly and 3.82% within SS and 3.90% within FS volumetrically compared to the initial design parameters. CONCLUSION: The linear and volumetric dimensional changes did not differ significantly between standard and fast sintering protocols, and the preparation designs had more influence on the dimensional changes compared to sintering protocols.