PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581-592.

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. Automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their method on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge (https://wmh.isi.uu.nl/). Sixty T1+FLAIR images from three MR scanners were released with manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. Segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: (1) Dice similarity coefficient, (2) modified Hausdorff distance (95th percentile), (3) absolute log-transformed volume difference, (4) sensitivity for detecting individual lesions, and (5) F1-score for individual lesions. Additionally, methods were ranked on their inter-scanner robustness.Twenty participants submitted their method for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all methods generalize to unseen scanners.The challenge remains open for future submissions and provides a public platform for method evaluation.

Cerebral small vessel disease (SVD) is an important cause of cognitive impairment. Important MRI manifestations of SVD include white matter hyperintensities (WMH) and lacunes. This narrative review addresses the role of anatomical lesion location in the impact of SVD on cognition, integrating findings from early autopsy studies with emerging findings from recent studies with advanced image analysis techniques. Early autopsy and imaging studies of small case series indicate that single lacunar infarcts in, for example the thalamus, caudate nucleus or internal capsule can cause marked cognitive impairment. However, the findings of such case studies may not be generalizable. Emerging location-based image analysis approaches are now being applied to large cohorts. Recent studies show that WMH burden in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation (ATR), is more relevant in explaining variance in cognitive functioning than global WMH volume. These findings suggest that the future diagnostic work-up of memory clinic patients could potentially be improved by shifting from a global assessment of WMH and lacune burden towards a quantitative assessment of lesion volumes within strategic brain regions. In this review, a summary of currently known strategic regions for SVD-related cognitive impairment is provided, highlighting recent technical developments in SVD research. The potential and challenges of location-based approaches for diagnostic purposes in clinical practice are discussed, along with their potential prognostic and therapeutic applications.

Semantic and phonemic fluency tasks are frequently used to test executive functioning, speed and attention, and access to the mental lexicon. In semantic fluency tasks, subjects are required to generate words belonging to a category (e.g., animals) within a limited time window, whereas in phonemic fluency tasks subjects have to generate words starting with a given letter. Anatomical correlates of semantic and phonemic fluency are currently assumed to overlap in left frontal structures, reflecting shared executive processes, and to be distinct in left temporal and right frontal structures, reflecting involvement of distinct memory processes and search strategies. Definite evidence for this assumption is lacking. To further establish the anatomical correlates of semantic and phonemic fluency, we applied assumption-free voxel-based and region-of-interest-based lesion-symptom mapping in 93 patients with ischemic stroke. Fluency was assessed by asking patients to name animals (semantic), and words starting with the letter N and A (phonemic). Our findings indicate that anatomical correlates of semantic and phonemic fluency overlap in the left inferior frontal gyrus and insula, reflecting shared underlying cognitive processes. Phonemic fluency additionally draws on the left rolandic operculum, which might reflect a search through phonological memory, and the middle frontal gyrus. Semantic fluency additionally draws on left medial temporal regions, probably reflecting a search through semantic memory, and the right inferior frontal gyrus, which might reflect the application of a visuospatial mental imagery strategy in semantic fluency. These findings establish shared and distinct anatomical correlates of semantic and phonemic fluency.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-015-1033-8) contains supplementary material, which is available to authorized users.