White matter changes and gait decline in cerebral small vessel disease.

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (ß = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, ß = - 0.14, p = 0.009; ß = - 0.12, p = 0.018; ß = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

Automated detection of cerebral microbleeds in patients with Traumatic Brain Injury.

In this paper a Computer Aided Detection (CAD) system is presented to automatically detect Cerebral Microbleeds (CMBs) in patients with Traumatic Brain Injury (TBI). It is believed that the presence of CMBs has clinical prognostic value in TBI patients. To study the contribution of CMBs in patient outcome, accurate detection of CMBs is required. Manual detection of CMBs in TBI patients is a time consuming task that is prone to errors, because CMBs are easily overlooked and are difficult to distinguish from blood vessels. This study included 33 TBI patients. Because of the laborious nature of manually annotating CMBs, only one trained expert manually annotated the CMBs in all 33 patients. A subset of ten TBI patients was annotated by six experts. Our CAD system makes use of both Susceptibility Weighted Imaging (SWI) and T1 weighted magnetic resonance images to detect CMBs. After pre-processing these images, a two-step approach was used for automated detection of CMBs. In the first step, each voxel was characterized by twelve features based on the dark and spherical nature of CMBs and a random forest classifier was used to identify CMB candidate locations. In the second step, segmentations were made from each identified candidate location. Subsequently an object-based classifier was used to remove false positive detections of the voxel classifier, by considering seven object-based features that discriminate between spherical objects (CMBs) and elongated objects (blood vessels). A guided user interface was designed for fast evaluation of the CAD system result. During this process, an expert checked each CMB detected by the CAD system. A Fleiss' kappa value of only 0.24 showed that the inter-observer variability for the TBI patients in this study was very large. An expert using the guided user interface reached an average sensitivity of 93%, which was significantly higher (p = 0.03) than the average sensitivity of 77% (sd 12.4%) that the six experts manually detected. Furthermore, with the use of this CAD system the reading time was substantially reduced from one hour to 13 minutes per patient, because the CAD system only detects on average 25.9 false positives per TBI patient, resulting in 0.29 false positives per definite CMB finding.