Objective: The Alzheimer's continuum is biologically defined by beta-amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co-occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid-related white matter changes in preclinical Alzheimer disease. Methods: Cognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta-amyloid-negative (ABÀ) and -positive (AB+) participants differed on DKIbased conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra-axonal radial diffusivity [D e,⊥ ]) metrics, and whether these metrics were associated with other biomarkers. Results: We found significantly greater diffusion restriction (higher FA/AWF, lower MD/D e,⊥ ) in white matter in AB+ than ABÀ (partial η 2 =0.08-0.19), more notably in the extra-axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas D e,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume. Interpretation: These results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration.
The clinicopathological study of five autopsied cases of Marchiafava-Bignami disease is reported. The demyelination of the central portion of the corpus callosum is the major characteristics of the disease. In two cases the demyelination also involved the anterior and posterior commissures. There is a clear relationship to alcoholism and malnutrition in the cases reported in the present study.
Purpose The purpose of this preliminary study is to apply diffusional kurtosis imaging to assess the early response of recurrent glioblastoma to bevacizumab treatment. Methods This prospective cohort study included 10 patients who had been diagnosed with recurrent glioblastoma and scheduled to receive bevacizumab treatment. Diffusional kurtosis images were obtained from all the patients 0–7 days before (pre-bevacizumab) and 28 days after (post-bevacizumab) initiating bevacizumab treatment. The mean, 10th, and 90th percentile values were derived from the histogram of diffusional kurtosis imaging metrics in enhancing and non-enhancing lesions, selected on post-contrast T1-weighted and fluid-attenuated inversion recovery images. Correlations of imaging measures with progression-free survival and overall survival were evaluated using Spearman's rank correlation coefficient. The significance level was set at P < 0.05. Results Higher pre-bevacizumab non-enhancing lesion volume was correlated with poor overall survival ( r = −0.65, P = 0.049). Higher post-bevacizumab mean diffusivity and axial diffusivity (D∥, D∥10% and D∥90%) in non-enhancing lesions were correlated with poor progression-free survival ( r = −0.73, −0.83, −0.71 and −0.85; P < 0.05). Lower post-bevacizumab axial kurtosis (K∥10%) in non-enhancing lesions was correlated with poor progression-free survival ( r = 0.81, P = 0.008). Conclusions This preliminary study demonstrates that diffusional kurtosis imaging metrics allow the detection of tissue changes 28 days after initiating bevacizumab treatment and that they may provide information about tumor progression.
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