@article {aCasamitjanac, title = {Projection to Latent Spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer{\textquoteright}s disease}, journal = {Frontiers in Neurology, section Applied Neuroimaging}, volume = {11}, year = {2020}, month = {07/2020}, chapter = {648}, abstract = {

Alzheimer{\textquoteright}s disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers such as cerebrospinal fluid (CSF) levels of Aβ, p-tau and t-tau. In parallel, brain anatomy can be characterized through imaging techniques such as magnetic resonance imaging (MRI). In this work, we relate both sets of measurements seeking associations between biomarkers and brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we use the projection to latent structures (PLS)\ method. Using PLS, we find a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We look for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we use a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We apply this technique to the study of subjects in the whole AD continuum from the preclinical asymptomatic stages all through to the symptomatic groups. Subsequent analyses involve splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitive impaired subjects (MCI) and dementia subjects (AD-dementia) where all symptoms are due to AD.

}, keywords = {Alzheimer{\textquoteright}s disease, brain morphology, CSF biomarkers, Latent model, PLS, preclinical AD}, author = {Adri{\`a} Casamitjana and Paula Petrone and Jose Luis Molinuevo and Juan D. Gispert and Ver{\'o}nica Vilaplana} } @article {aPetrone, title = {Prediction of amyloid pathology in cognitively unimpaired individuals using voxelwise analysis of longitudinal structural brain MRI}, journal = {Alzheimer{\textquoteright}s Research \& Therapy}, volume = {11}, year = {2019}, month = {12/2019}, abstract = {

Background: Magnetic resonance imaging (MRI) has unveiled specific alterations at different stages of Alzheimer{\textquoteright}s disease (AD) pathophysiologic continuum constituting what has been established as {\textquoteleft}AD signature{\textquoteright}. To what extent MRI can detect amyloid-related cerebral changes from structural MRI in cognitively unimpaired individuals is still an area open for exploration.

Method: Longitudinal 3D-T1 MRI scans were acquired from a subset of the ADNI cohort comprising 403 subjects: 79 controls (Ctrls), 50 preclinical AD (PreAD), 274 MCI and dementia due to AD (MCI/AD). Amyloid CSF was used as gold-standard measure with established cut-offs (\<192pg/mL) to establish diagnostic categories. Cognitively unimpaired individuals were defined as Ctrls if were amyloid negative and PreAD otherwise. The MCI/AD group was amyloid positive. Only subjects with the same diagnostic category at baseline and follow-up visits were considered for the study. Longitudinal morphometric analysis was performed using SPM12 to calculate Jacobian determinant maps. Statistical analysis was carried out on these jacobian maps to identify structural changes that were significantly different between diagnostic categories. A machine learning classifier was applied on Jacobian determinant maps to predict the presence of abnormal amyloid levels in cognitively unimpaired individuals. The performance of this classifier was evaluated using receiver operating characteristic curve analysis and as a function of the follow-up time between MRI scans. We applied a cost function to assess the benefit of using this classifier in the triaging of individuals in a clinical trial-recruitment setting.

Results: The optimal follow-up time for classification of Ctrls vs PreAD was Δt\>2.5 years and hence, only subjects within this temporal span are used for evaluation (15 Ctrls, 10 PreAD). The longitudinal voxel-based classifier achieved an AUC=0.87 (95\%CI:0.72-0.97). The brain regions that showed the highest discriminative power to detect amyloid abnormalities were the medial, inferior and lateral temporal lobes, precuneus, caudate heads, basal forebrain and lateral ventricles.

Conclusions: Our work supports that machine learning applied to longitudinal brain volumetric changes can be used to predict, with high precision, presence of amyloid abnormalities in cognitively unimpaired subjects. Used as a triaging method to identify a fixed number of amyloid positive individuals, this longitudinal voxelwise classifier is expected to avoid 55\% of unnecessary CSF and/or PET scans and reduce economic cost by 40\%.

}, doi = {https://doi.org/10.1186/s13195-019-0526-8}, url = {https://link.springer.com/article/10.1186/s13195-019-0526-8}, author = {Paula Petrone and Adri{\`a} Casamitjana and Carles Falcon and Miguel Artigues C{\`a}naves and G. Operto and R. Cacciaglia and Jose Luis Molinuevo and Ver{\'o}nica Vilaplana and Juan D. Gispert} } @mastersthesis {xCanaves18, title = {Prevention of Alzheimer{\textquoteright}s Disease: a contribution from MRI and machine learning}, year = {2018}, abstract = {

Alzheimer{\textquoteright}s disease (AD) is a neurodegenerative disease and the leading cause of dementia (50-70\% of cases). Despite worldwide efforts, there is no progress in developing a cure for AD and dementia. Machine learning, hand in hand with magnetic resonance imaging (MRI), come to the aid of disease diagnostics. In the scope of AD, many efforts have been dedicated to the automated detection of mild-cognitive impairment and dementia. In our research, instead we focus on the prediction of AD in its preclinical stage using machine learning classification. Another key innovation is that we will work with a longitudinal pipeline. In addition to classification, the project focuses on detecting the most relevant imaging voxels for classification, that is, to help us locate where AD-specific structural brain changes occur. We have improved classification performance i n comparison with results obtained with cross-sectional datasets in previous studies and we have identified possible regions of interest based on feature scores obtained from feature selection.

}, author = {Miguel Artigues C{\`a}naves}, editor = {Paula Petrone and Ver{\'o}nica Vilaplana} }