Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer’s disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with in total 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e.g., the Alzheimer’s Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease. Methods Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis. Results A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository. Conclusions The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.

Because hypoperfusion of brain tissue precedes atrophy in dementia, the detection of dementia may be advanced by the use of perfusion information. Such information can be obtained noninvasively with arterial spin labeling (ASL), a relatively new MR technique quantifying cerebral blood flow (CBF). Using ASL and structural MRI, we evaluated diagnostic classification in 32 prospectively included presenile early stage dementia patients and 32 healthy controls. Patients were suspected of Alzheimer's disease (AD) or frontotemporal dementia. Classification was based on CBF as perfusion marker, gray matter (GM) volume as atrophy marker, and their combination. These markers were each examined using six feature extraction methods: a voxel-wise method and a region of interest (ROI)-wise approach using five ROI-sets in the GM. These ROI-sets ranged in number from 72 brain regions to a single ROI for the entire supratentorial brain. Classification was performed with a linear support vector machine classifier. For validation of the classification method on the basis of GM features, a reference dataset from the AD Neuroimaging Initiative database was used consisting of AD patients and healthy controls. In our early stage dementia population, the voxelwise feature-extraction approach achieved more accurate results (area under the curve (AUC) range = 86 - 91%) than all other approaches (AUC = 57 - 84%). Used in isolation, CBF quantified with ASL was a good diagnostic marker for dementia. However, our findings indicated only little added diagnostic value when combining ASL with the structural MRI data (AUC = 91%), which did not significantly improve over accuracy of structural MRI atrophy marker by itself.

ObjectivesTo investigate the added diagnostic value of arterial spin labelling (ASL) and diffusion tensor imaging (DTI) to structural MRI for computer-aided classification of Alzheimer's disease (AD), frontotemporal dementia (FTD), and controls.MethodsThis retrospective study used MRI data from 24 early-onset AD and 33 early-onset FTD patients and 34 controls (CN). Classification was based on voxel-wise feature maps derived from structural MRI, ASL, and DTI. Support vector machines (SVMs) were trained to classify AD versus CN (AD-CN), FTD-CN, AD-FTD, and AD-FTD-CN (multi-class). Classification performance was assessed by the area under the receiver-operating-characteristic curve (AUC) and accuracy. Using SVM significance maps, we analysed contributions of brain regions.ResultsCombining ASL and DTI with structural MRI resulted in higher classification performance for differential diagnosis of AD and FTD (AUC = 84%; p = 0.05) than using structural MRI by itself (AUC = 72%). The performance of ASL and DTI themselves did not improve over structural MRI. The classifications were driven by different brain regions for ASL and DTI than for structural MRI, suggesting complementary information.ConclusionsASL and DTI are promising additions to structural MRI for classification of early-onset AD, early-onset FTD, and controls, and may improve the computer-aided differential diagnosis on a single-subject level.Key points• Multiparametric MRI is promising for computer-aided diagnosis of early-onset AD and FTD. • Diagnosis is driven by different brain regions when using different MRI methods. • Combining structural MRI, ASL, and DTI may improve differential diagnosis of dementia. Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-016-4691-x) contains supplementary material, which is available to authorized users.