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Background: In many retrospective studies and large clinical trials, high-resolution, good-contrast 3DT1 images are unavailable, hampering detailed analysis of brain atrophy. Ventricular enlargement then provides a sensitive indirect measure of ongoing central brain atrophy. Validated automated methods are required that can reliably measure ventricular enlargement and are robust across magnetic resonance (MR) image types. Aim: To validate the automated method VIENA for measuring the percentage ventricular volume change (PVVC) between two scans. Materials and Methods: Accuracy was assessed using four image types, acquired in 15 elderly patients (five with Alzheimer's disease, five with mild cognitive impairment, and five cognitively normal elderly) and 58 patients with multiple sclerosis (MS), by comparing PVVC values from VIENA to manual outlining. Precision was assessed from data with three imaging time points per MS patient, by measuring the difference between the direct (one-step) and indirect (two-step) measurement of ventricular volume change between the first and last time points. The stringent concordance correlation coefficient (CCC) was used to quantify absolute agreement. Results: CCC of VIENA with manual measurement was 0.84, indicating good absolute agreement. The median absolute difference between two-step and one-step measurement with VIENA was 1.01%, while CCC was 0.98. Neither initial ventricular volume nor ventricular volume change affected performance of the method. Discussion: VIENA has good accuracy and good precision across four image types. VIENA therefore provides a useful fully automated method for measuring ventricular volume change in large datasets. Conclusion: VIENA is a robust, accurate, and precise method for measuring ventricular volume change. Hum Brain Mapp 35:1101–1110, 2014. © 2013 Wiley Periodicals, Inc.

BACKGROUND: Cerebral microbleeds (MBs) are commonly observed in memory clinic patients. Little is known about occurrence of and risk factors for developing new MBs in this population. OBJECTIVE: To investigate incidence of lobar and nonlobar MBs in a memory clinic population. Furthermore, to assess risk factors for the development of new MBs and their associations with other MRI changes. METHODS: A total of 254 patients visiting our memory clinic, with repeat gradient-recalled echo T2*-weighted MRI, were included (scan interval 1.9 +/- 0.9 years). Baseline and incident MBs were regionally counted. White matter hyperintensities (WMH) and progression of WMH were assessed using visual rating scales. Baseline brain volume and whole-brain atrophy rate were estimated automatically. In a subset, APOE was determined. RESULTS: Thirty-one (12%) patients developed new MBs (range 1-19). Both multiple strictly lobar and nonlobar MBs at baseline predicted incident MBs (odds ratio [OR] 8.4; 95% confidence interval [CI] 2.2-33.2, and OR 33.8; 95% CI 8.1-140.8). Furthermore, baseline WMH grade (OR 1.2; 1.1-1.3), lacunar infarcts (OR 2.8; 1.3-6.0), and APOE epsilon2 carriership (OR 4.2; 1.4-12.5) predicted MB incidence. Incident MB patients had more progression of WMH (p < 0.01) and incident lacunar infarcts (p < 0.05). These relations were most prominent for incident nonlobar MBs. Incident strictly lobar MBs were associated with smoking. CONCLUSION: In addition to APOE genotype, presence and progression of small-vessel disease and vascular risk factors were predictors of new MBs. The latter are potentially modifiable, suggesting the possibility of preventing incident MBs, hopefully resulting in slower clinical decline.

Objective: To investigate whether baseline CSF biomarkers are associated with hippocampal atrophy rate as a measure of disease progression in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls, controlling for baseline neuropsychological and MRI findings.Methods: We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls (mean age 68 +/- 8 years; 39 [52%] female) who visited our memory clinic and had received serial MRI scanning (scan interval 1.7 +/- 0.7 years). At baseline, CSF biomarkers (amyloid beta 1-42, tau, and tau phosphorylated at threonine 181 [p-tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were assessed using visual rating scales for medial temporal lobe atrophy (MTA), global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy rates were estimated using regional nonlinear "fluid" registration of follow-up scan to baseline scan.Results: Stepwise multiple linear regression, adjusted for age and sex, showed that increased CSF p-tau levels (beta [standard error]: - 0.79 [0.35]) at baseline was independently associated with higher subsequent hippocampal atrophy rates (p < 0.05), together with poorer memory performance (0.09 [0.04]) and more severe MTA (- 0.60 [0.21]). The association of memory function with hippocampal atrophy rate was explained by the link with diagnosis, because it disappeared from the model after we additionally corrected for diagnosis.Conclusions: Baseline CSF levels of tau phosphorylated at threonine 181 are independently associated with subsequent disease progression, as reflected by hippocampal atrophy rate. This effect is independent of baseline neuropsychological and MRI predictors. Our results imply that predicting disease progression can best be achieved by combining information from different modalities. Neurology (R) 2009;73:935-940

Objective To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS). Design From eight MAGNIMS (MAGNetic resonance Imaging in MS) centres, we retrospectively included 261 MS patients with MR imaging at baseline and after 1–2 years, and Expanded Disability Status Scale (EDSS) scoring at baseline and after 10 years. Annualised whole brain atrophy, central brain atrophy rates and T2 lesion volumes were calculated. Patients were categorised by baseline diagnosis as primary progressive MS (n=77), clinically isolated syndromes (n=18), relapsing–remitting MS (n=97) and secondary progressive MS (n=69). Relapse onset patients were classified as minimally impaired (EDSS=0–3.5, n=111) or moderately impaired (EDSS=4–6, n=55) according to their baseline disability (and regardless of disease type). Linear regression models tested whether whole brain and central atrophy, lesion volumes at baseline, follow-up and lesion volume change predicted 10 year EDSS and MS Severity Scale scores. Results In the whole patient group, whole brain and central atrophy predicted EDSS at 10 years, corrected for imaging protocol, baseline EDSS and disease modifying treatment. The combined model with central atrophy and lesion volume change as MRI predictors predicted 10 year EDSS with R 2 =0.74 in the whole group and R 2 =0.72 in the relapse onset group. In subgroups, central atrophy was predictive in the minimally impaired relapse onset patients (R 2 =0.68), lesion volumes in moderately impaired relapse onset patients (R 2 =0.21) and whole brain atrophy in primary progressive MS (R 2 =0.34). Conclusions This large multicentre study points to the complementary predictive value of atrophy and lesion volumes for predicting long term disability in MS.

To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls.We included 64 patients with AD (67 +/- 9 years; F/M 38/26), 44 patients with MCI (71 +/- 6 years; 21/23), and 34 controls (67 +/- 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 +/- 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools.All MRI measures differed between groups (p0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5-22.2]), hippocampal atrophy rate (5.2 [1.9-14.3]), and whole brain atrophy rate (2.8 [1.1-7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1-606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression.Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD.