Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease.

BACKGROUND: Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. METHODS: We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. RESULTS: The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co. CONCLUSIONS: Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.

Automatic temporal lobe atrophy assessment in prodromal AD: Data from the DESCRIPA study.

BACKGROUND: In the framework of the clinical validation of research tools, this investigation presents a validation study of an automatic medial temporal lobe atrophy measure that is applied to a naturalistic population sampled from memory clinic patients across Europe. METHODS: The procedure was developed on 1.5-T magnetic resonance images from the Alzheimer's Disease Neuroimaging Initiative database, and it was validated on an independent data set coming from the DESCRIPA study. All images underwent an automatic processing procedure to assess tissue atrophy that was targeted at the hippocampal region. For each subject, the procedure returns a classification index. Once provided with the clinical assessment at baseline and follow-up, subjects were grouped into cohorts to assess classification performance. Each cohort was divided into converters (co) and nonconverters (nc) depending on the clinical outcome at follow-up visit. RESULTS: We found the area under the receiver operating characteristic curve (AUC) was 0.81 for all co versus nc subjects, and AUC was 0.90 for subjective memory complaint (SMCnc) versus all co subjects. Furthermore, when training on mild cognitive impairment (MCI-nc/MCI-co), the classification performance generally exceeds that found when training on controls versus Alzheimer's disease (CTRL/AD). CONCLUSIONS: Automatic magnetic resonance imaging analysis may assist clinical classification of subjects in a memory clinic setting even when images are not specifically acquired for automatic analysis.

Local MRI analysis approach in the diagnosis of early and prodromal Alzheimer's disease.

BACKGROUND: Medial temporal lobe (MTL) atrophy is one of the key biomarkers to detect early neurodegenerative changes in the course of Alzheimer's disease (AD). There is active research aimed at identifying automated methodologies able to extract accurate classification indexes from T1-weighted magnetic resonance images (MRI). Such indexes should be fit for identifying AD patients as early as possible. SUBJECTS: A reference group composed of 144AD patients and 189 age-matched controls was used to train and test the procedure. It was then applied on a study group composed of 302 MCI subjects, 136 having progressed to clinically probable AD (MCI-converters) and 166 having remained stable or recovered to normal condition after a 24month follow-up (MCI-non converters). All subjects came from the ADNI database. METHODS: We sampled the brain with 7 relatively small volumes, mainly centered on the MTL, and 2 control regions. These volumes were filtered to give intensity and textural MRI-based features. Each filtered region was analyzed with a Random Forest (RF) classifier to extract relevant features, which were subsequently processed with a Support Vector Machine (SVM) classifier. Once a prediction model was trained and tested on the reference group, it was used to compute a classification index (CI) on the MCI cohort and to assess its accuracy in predicting AD conversion in MCI patients. The performance of the classification based on the features extracted by the whole 9 volumes is compared with that derived from each single volume. All experiments were performed using a bootstrap sampling estimation, and classifier performance was cross-validated with a 20-fold paradigm. RESULTS: We identified a restricted set of image features correlated with the conversion to AD. It is shown that most information originate from a small subset of the total available features, and that it is enough to give a reliable assessment. We found multiple, highly localized image-based features which alone are responsible for the overall clinical diagnosis and prognosis. The classification index is able to discriminate Controls from AD with an Area Under Curve (AUC)=0.97 (sensitivity ≃89% at specificity ≃94%) and Controls from MCI-converters with an AUC=0.92 (sensitivity ≃89% at specificity ≃80%). MCI-converters are separated from MCI-non converters with AUC=0.74(sensitivity ≃72% at specificity ≃65%). FINDINGS: The present automated MRI-based technique revealed a strong relationship between highly localized baseline-MRI features and the baseline clinical assessment. In addition, the classification index was also used to predict the probability of AD conversion within a time frame of two years. The definition of a single index combining local analysis of several regions can be useful to detect AD neurodegeneration in a typical MCI population.

Automatic analysis of medial temporal lobe atrophy from structural MRIs for the early assessment of Alzheimer disease.

The purpose of this study is to develop a software for the extraction of the hippocampus and surrounding medial temporal lobe (MTL) regions from T1-weighted magnetic resonance (MR) images with no interactive input from the user, to introduce a novel statistical indicator, computed on the intensities in the automatically extracted MTL regions, which measures atrophy, and to evaluate the accuracy of the newly developed intensity-based measure of MTL atrophy to (a) distinguish between patients with Alzheimer disease (AD), patients with amnestic mild cognitive impairment (aMCI), and elderly controls by using established criteria for patients with AD and aMCI as the reference standard and (b) infer about the clinical outcome of aMCI patients. For the development of the software, the study included 61 patients with mild AD (17 men, 44 women; mean age +/- standard deviation (SD), 75.8 years +/- 7.8; Mini Mental State Examination (MMSE) score, 24.1 +/- 3.1), 42 patients with aMCI (11 men, 31 women; mean age +/- SD, 75.2 years +/- 4.9; MMSE score, 27.9 +/- 1.9), and 30 elderly healthy controls (10 men, 20 women; mean age +/- SD, 74.7 years +/- 5.2; MMSE score, 29.1 +/- 0.8). For the evaluation of the statistical indicator, 150 patients with mild AD (62 men, 88 women; mean age +/- SD, 76.3 years +/- 5.8; MMSE score, 23.2 +/- 4.1), 247 patients with aMCI (143 men, 104 women; mean age +/- SD, 75.3 years +/- 6.7; MMSE score, 27.0 +/- 1.8), and 135 elderly healthy controls (61 men, 74 women; mean age +/- SD, 76.4 years +/- 6.1). Fifty aMCI patients were evaluated every 6 months over a 3 year period to assess conversion to AD. For each participant, two subimages of the MTL regions were automatically extracted from T1-weighted MR images with high spatial resolution. An intensity-based MTL atrophy measure was found to separate control, MCI, and AD cohorts. Group differences were assessed by using two-sample t test. Individual classification was analyzed by using receiver operating characteristic (ROC) curves. Compared to controls, significant differences in the intensity-based MTL atrophy measure were detected in both groups of patients (AD vs controls, 0.28 +/- 0.03 vs 0.34 +/- 0.03, P < 0.001; aMCI vs controls, 0.31 +/- 0.03 vs 0.34 +/- 0.03, P < 0.001). Moreover, the subgroup of aMCI converters was significantly different from controls (0.27 +/- 0.034 vs 0.34 +/- 0.03, P < 0.001). Regarding the ROC curve for intergroup discrimination, the area under the curve was 0.863 for AD patients vs controls, 0.746 for all aMCI patients vs controls, and 0.880 for aMCI converters vs controls. With specificity set at 85%, the sensitivity was 74% for AD vs controls, 45% for aMCI vs controls, and 83% for aMCI converters vs controls. The automated analysis of MTL atrophy in the segmented volume is applied to the early assessment of AD, leading to the discrimination of aMCI converters with an average 3 year follow-up. This procedure can provide additional useful information in the early diagnosis of AD.