Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus

Aims/hypothesis: Type 2 diabetes mellitus has been associated with brain atrophy and cognitive decline, but the association with ischaemic white matter lesions is unclear. Previous neuroimaging studies have mainly used semiquantitative rating scales to measure atrophy and white matter lesions (WMLs). In this study we used an automated segmentation technique to investigate the association of type 2 diabetes, several diabetes-related risk factors and cognition with cerebral tissue and WML volumes. Subjects and methods: Magnetic resonance images of 99 patients with type 2 diabetes and 46 control participants from a population-based sample were segmented using a k-nearest neighbour classifier trained on ten manually segmented data sets. White matter, grey matter, lateral ventricles, cerebrospinal fluid not including lateral ventricles, and WML volumes were assessed. Analyses were adjusted for age, sex, level of education and intracranial volume. Results: Type 2 diabetes was associated with a smaller volume of grey matter (-21.8 ml; 95% CI -34.2, -9.4) and with larger lateral ventricle volume (7.1 ml; 95% CI 2.3, 12.0) and with larger white matter lesion volume (56.5%; 95% CI 4.0, 135.8), whereas white matter volume was not affected. In separate analyses for men and women, the effects of diabetes were only significant in women. Conclusions/interpretation: The combination of atrophy with larger WML volume indicates that type 2 diabetes is associated with mixed pathology in the brain. The observed sex differences were unexpected and need to be addressed in further studies. © 2007 Springer-Verlag

Automated white matter hyperintensity segmentation using Bayesian Model Selection: assessment and correlations with cognitive change

Accurate, automated white matter hyperintensity (WMH) segmentations are needed for large-scale studies to understand contributions of WMH to neurological diseases. We evaluated Bayesian Model Selection (BaMoS), a hierarchical fully-unsupervised model selection framework for WMH segmentation. We compared BaMoS segmentations to semi-automated segmentations, and assessed whether they predicted longitudinal cognitive change in control, early Mild Cognitive Impairment (EMCI), late Mild Cognitive Impairment (LMCI), subjective/significant memory concern (SMC) and Alzheimer’s (AD) participants. Data were downloaded from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Magnetic resonance images from 30 control and 30 AD participants were selected to incorporate multiple scanners, and were semi-automatically segmented by 4 raters and BaMoS. Segmentations were assessed using volume correlation, Dice score, and other spatial metrics. Linear mixed-effect models were fitted to 180 control, 107 SMC, 320 EMCI, 171 LMCI and 151 AD participants separately in each group, with the outcomes being cognitive change (e.g. mini-mental state examination; MMSE), and BaMoS WMH, age, sex, race and education used as predictors. There was a high level of agreement between BaMoS’ WMH segmentation volumes and a consensus of rater segmentations, with a median Dice score of 0.74 and correlation coefficient of 0.96. BaMoS WMH predicted cognitive change in: control, EMCI, and SMC groups using MMSE; LMCI using clinical dementia rating scale; and EMCI using Alzheimer’s disease assessment scale-cognitive subscale (p < 0.05, all tests). BaMoS compares well to semi-automated segmentation, is robust to different WMH loads and scanners, and can generate volumes which predict decline. BaMoS can be applicable to further large-scale studies

Methodological considerations on tract-based spatial statistics (TBSS)

Having gained a tremendous amount of popularity since its introduction in 2006, tract-based spatial statistics (TBSS) can now be considered as the standard approach for voxel-based analysis (VBA) of diffusion tensor imaging (DTI) data. Aiming to improve the sensitivity, objectivity, and interpretability of multi-subject DTI studies, TBSS includes a skeletonization step that alleviates residual image misalignment and obviates the need for data smoothing. Although TBSS represents an elegant and user-friendly framework that tackles numerous concerns existing in conventional VBA methods, it has limitations of its own, some of which have already been detailed in recent literature. In this work, we present general methodological considerations on TBSS and report on pitfalls that have not been described previously. In particular, we have identified specific assumptions of TBSS that may not be satisfied under typical conditions. Moreover, we demonstrate that the existence of such violations can severely affect the reliability of TBSS results. With TBSS being used increasingly, it is of paramount importance to acquaint TBSS users with these concerns, such that a well-informed decision can be made as to whether and how to pursue a TBSS analysis. Finally, in addition to raising awareness by providing our new insights, we provide constructive suggestions that could improve the validity and increase the impact of TBSS drastically

Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI: Rationale and design of the “ZOOM@SVDs” study

Background: Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves. Objective: This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs. Methods: ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs. Discussion: ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990–2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years’ diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology