Morphological Factor Estimation via High-Dimensional Reduction: Prediction of MCI Conversion to Probable AD

We propose a novel morphological factor estimate from structural MRI for disease state evaluation. We tested this methodology in the context of Alzheimer's disease (AD) with 349 subjects. The method consisted in (a) creating a reference MRI feature eigenspace using intensity and local volume change data from 149 healthy, young subjects; (b) projecting MRI data from 75 probable AD, 76 controls (CTRL), and 49 Mild Cognitive Impairment (MCI) in that space; (c) extracting high-dimensional discriminant functions; (d) calculating a single morphological factor based on various models. We used this methodology in leave-one-out experiments to (1) confirm the superiority of an inverse-squared model over other approaches; (2) obtain accuracy estimates for the discrimination of probable AD from CTRL (90%) and the prediction of conversion of MCI subjects to probable AD (79.4%)

Predicting Alzheimer's disease development : a comparison of cognitive criteria and associated neuroimaging biomarkers

Introduction: The definition of “objective cognitive impairment” in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer’s disease (AD) from baseline to 24 months. Methods: The sensitivity and specificity of six methods of defining episodic memory impairment (< −1, −1.5 or −2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer’s Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOEε4 status) was investigated using logistic regression. Results: Baseline scores < −1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE ε4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < −1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = −15.97, SE = 7.58, p = .035), and APOEε4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < −2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE ε4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy. Conclusions: Episodic memory impairment in MCI should be defined as scores < −1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE ε4 status can further improve prediction

Label Fusion Strategy Selection

Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques—STAPLE, Voting, and Shape-Based Averaging (SBA)—and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall

Normative data for subcortical regional volumes over the lifetime of the adult human brain

Normative data for volumetric estimates of brain structures are necessary to adequately assess brain volume alterations in individuals with suspected neurological or psychiatric conditions. Although many studies have described age and sex effects in healthy individuals for brain morphometry assessed via magnetic resonance imaging, proper normative values allowing to quantify potential brain abnormalities are needed. We developed norms for volumetric estimates of subcortical brain regions based on cross-sectional magnetic resonance scans from 2790 healthy individuals aged 18 to 94 years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting subcortical regional volumes of each hemisphere were produced including age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The mean explained variance by the models was 48%. For most regions, age, sex and eTIV predicted most of the explained variance while manufacturer, magnetic field strength and interactions predicted a limited amount. Estimates of the expected volumes of an individual based on its characteristics and the scanner characteristics can be obtained using derived formulas. For a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume can be obtained. Normative values were validated in independent samples of healthy adults and in adults with Alzheimer's disease and schizophrenia

Brain atrophy and patch-based grading in individuals from the CIMA-Q study : a progressive continuum from subjective cognitive decline to AD

It has been proposed that individuals developing Alzheimer’s disease (AD) first experience a phase expressing subjective complaints of cognitive decline (SCD) without objective cognitive impairment. Using magnetic resonance imaging (MRI), our objective was to verify whether SNIPE probability grading, a new MRI analysis technique, would distinguish between clinical dementia stage of AD: Cognitively healthy controls without complaint (CH), SCD, mild cognitive impairment, and AD. SNIPE score in the hippocampus and entorhinal cortex was applied to anatomical T1-weighted MRI of 143 participants from the Consortium pour l’identification précoce de la maladie Alzheimer - Québec (CIMA-Q) study and compared to standard atrophy measures (volumes and cortical thicknesses). Compared to standard atrophy measures, SNIPE score appeared more sensitive to differentiate clinical AD since differences between groups reached a higher level of significance and larger effect sizes. However, no significant difference was observed between SCD and CH groups. Combining both types of measures did not improve between-group differences. Further studies using a combination of biomarkers beyond anatomical MRI might be needed to identify individuals with SCD who are on the beginning of the clinical continuum of AD

FreeSurfer cortical normative data for adults using Desikan-Killiany-Tourville and ex vivo protocols

We recently built normative data for FreeSurfer morphometric estimates of cortical regions using its default atlas parcellation (Desikan-Killiany or DK) according to individual and scanner characteristics. We aimed to produced similar normative values for Desikan-Killianny-Tourville (DKT) and ex vivo-based labeling protocols, as well as examine the differences between these three atlases. Surfaces, thicknesses, and volumes of cortical regions were produced using cross-sectional magnetic resonance scans from the same 2713 healthy individuals aged 18 to 94 years as used in the reported DK norms. Models predicting regional cortical estimates of each hemisphere were produced using age, sex, estimated intracranial volume (eTIV), scanner manufacturer and magnetic field strength (MFS) as predictors. The DKT and DK models generally included the same predictors and produced similar R2. Comparison between DK, DKT, ex vivo atlases normative cortical measures showed that the three protocols generally produced similar normative values

Grid computing application for brain magnetic resonance image processing

This work emphasizes the use of grid computing and web technology for automatic postprocessing of brain magnetic resonance images (MRI) in the context of neuropsychiatric (Alzheimer’s disease) research. Post-acquisition image processing is achieved through the interconnection of several individual processes into pipelines. Each process has input and output data ports, options and execution parameters, and performs single tasks such as: a) extracting individual image attributes (e.g. dimensions, orientation, center of mass), b) performing image transformations (e.g. scaling, rotation, skewing, intensity standardization, linear and non-linear registration), c) performing image statistical analyses, and d) producing the necessary quality control images and/or files for user review. The pipelines are built to perform specific sequences of tasks on the alphanumeric data and MRIs contained in our database. The web application is coded in PHP and allows the creation of scripts to create, store and execute pipelines and their instances either on our local cluster or on high-performance computing platforms. To run an instance on an external cluster, the web application opens a communication tunnel through which it copies the necessary files, submits the execution commands and collects the results. We present result on system tests for the processing of a set of 821 brain MRIs from the Alzheimer's Disease Neuroimaging Initiative study via a nonlinear registration pipeline composed of 10 processes. Our results show successful execution on both local and external clusters, and a 4- fold increase in performance if using the external cluster. However, the latter’s performance does not scale linearly as queue waiting times and execution overhead increase with the number of tasks to be executed

Patch-wise brain age longitudinal reliability (2020)

We recently introduced a patch‐wise technique to estimate brain age from anatomical T1‐weighted magnetic resonance imaging (T1w MRI) data. Here, we sought to assess its longitudinal reliability by leveraging a unique dataset of 99 longitudinal MRI scans from a single, cognitively healthy volunteer acquired over a period of 17 years (aged 29–46 years) at multiple sites. We built a robust patch‐wise brain age estimation framework on the basis of 100 cognitively healthy individuals from the MindBoggle dataset (aged 19–61 years) using the Desikan‐Killiany‐Tourville atlas, then applied the model to the volunteer dataset. The results show a high prediction accuracy on the independent test set (R2 = .94, mean absolute error of 0.63 years) and no statistically significant difference between manufacturers, suggesting that the patch‐wise technique has high reliability and can be used for longitudinal multi‐centric studies

Unexpected pathways toward college graduation

This study examines the dispositions and experiences of support of college students associated with unexpected pathways toward college graduation. The final sample was drawn from a national sample of 3,998 youths who participated in a longitudinal project. Using the k-nearest neighbors’ algorithm, we created four groups based on the Québec High School Average and the College Graduation status four years after admission (Unexpected Graduates; Expected Dropouts; Unexpected Dropouts; Expected Graduates). Compared to ED, UG showed lower aggressive behaviors and attentional problems and higher participation in institutional or targeted support measures in college. They were also more likely to have attended a private high school. Compared to EG, UD showed lower academic behaviors and motivation, lower perceptions of teaching quality and support, and lower economic capital and support from family. They were also more likely to enrol in a technical college program and less likely to have attended a private high school