A fully automated method for quantifying and localizing white matter hyperintensities on MR images

Multiple brain morphometric changes have been reported in late-life depression (LLD), mostly in studies comparing volumes of circumscribed brain areas. The aim of our study is to characterize the volumetric changes of multiple gray matter regions in relation to age of onset/duration of illness. We predicted that the association of gray matter volumes with total duration of illness and age of onset would differ depending on whether the region was susceptible to the toxic effects of chronic exposure to cortisol or to the vascular/ neurodegenerative changes accompanying prodromal dementia. Seventy-one elderly depressed subjects were studied along with thirtytwo comparison subjects. High-resolution T1-weighted brain MRIs were processed using an automated labeling pathway technique. To protect against type-I error, we combined the right and left hemisphere volume data. We sampled 24 regions of interest (ROIs). We used the primary visual cortex volume to normalize for individual variations in brain size. LLD Subjects had smaller volumes than nondepressed subjects in 17 of the 24 examined ROIs. Shorter duration of illness and later age of onset was correlated with smaller volumes of parahippocampal area and parietal inferior area. A later age of onset was also correlated with smaller volumes of several frontal and temporal areas, cingulum, and putamen. Our findings support a dementia prodrome model more strongly than a toxic stress model in this group of subjects. However, it remains likely that both processes as well as other factors contribute to the heterogeneity of volumetric brain changes in LLD.

Objective: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.Methods: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.Results: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (b 5 20.27, p , 0.001) and to higher WMH (b 5 0.23, p 5 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p 5 0.043) in the mediation analyses.Conclusions: Sustained exposure to high IL-6 over 10 years rather than the rate of change in or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH. Increased levels of inflammatory cytokines such as interleukin-6 (IL-6) are cross-sectionally and longitudinally associated with poor physical function in older adults.1-5 IL-6 assayed at regular intervals over a long-term period may better capture sustained IL-6 exposure and rate of change rather than random assays spread apart over time. It is not known whether the sustained longterm exposure to IL-6 or rate of change in IL-6 contributes to the relationship between IL-6 and gait speed beyond a single concurrent indicator of inflammation.Higher IL-6 is linked to greater volume of white matter hyperintensities (WMH) on MRI in most studies [6][7][8] but not in all. 9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.

Abstract:The purpose of this study is to develop a semi-automated method to measure white matter lesion (WML) volumes in four different categories, and to assess the accuracy of the method. The four-category classification of white matter lesions has the potential of providing better etiological and functional relevance than the conventional two-category classification of periventricular and deep WMLs. The methodological steps are as follows. First, the Statistical Parametric Mapping (SPM) software is used to strip off the skull and scalp, and segment the FLAIR MR images of the brain into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Second, such segmentation is corrected manually. Third, the white matter is partitioned into four categories. Fourth, the mean, variance of each category is computed. Then the user selects a suitable threshold that differentiates WML from normal tissues. Finally, the WML volumes for each category are calculated. Three cases which represent mild, moderate and severe WML are used to test our proposed method. The overlap percentage between our method and the gold standard is 77%, which compares favorably with the best results of 62.2% published in the literature. Based on the test results, our semi-automated method is promising to be a useful tool in quantitative measurement of white matter lesions.