Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals.

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-α, HF-α) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age × sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-α and HF-α in middle-aged women compared with men (30-39 yr) and higher LF-α, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies.NEW & NOTEWORTHY In this study, we demonstrate that the age-related decrease of spontaneous baroreflex sensitivity is different in men and women by analyzing resting state cardiovascular data of a large sample of healthy individuals.

IMAGE-IN: Interactive web-based multidimensional 3D visualizer for multi-modal microscopy images.

Advances in microscopy hardware and storage capabilities lead to increasingly larger multidimensional datasets. The multiple dimensions are commonly associated with space, time, and color channels. Since "seeing is believing", it is important to have easy access to user-friendly visualization software. Here we present IMAGE-IN, an interactive web-based multidimensional (N-D) viewer designed specifically for confocal laser scanning microscopy (CLSM) and focused ion beam scanning electron microscopy (FIB-SEM) data, with the goal of assisting biologists in their visualization and analysis tasks and promoting digital workflows. This new visualization platform includes intuitive multidimensional opacity fine-tuning, shading on/off, multiple blending modes for volume viewers, and the ability to handle multichannel volumetric data in volume and surface views. The software accepts a sequence of image files or stacked 3D images as input and offers a variety of viewing options ranging from 3D volume/surface rendering to multiplanar reconstruction approaches. We evaluate the performance by comparing the loading and rendering timings of a heterogeneous dataset of multichannel CLSM and FIB-SEM images on two devices with installed graphic cards, as well as comparing rendered image quality between ClearVolume (the ImageJ open-source desktop viewer), Napari (the Python desktop viewer), Imaris (the closed-source desktop viewer), and our proposed IMAGE-IN web viewer.

DICOMization of Proprietary Files Obtained from Confocal, Whole-Slide, and FIB-SEM Microscope Scanners.

The evolution of biomedical imaging technology is allowing the digitization of hundreds of glass slides at once. There are multiple microscope scanners available in the market including low-cost solutions that can serve small centers. Moreover, new technology is being researched to acquire images and new modalities are appearing in the market such as electron microscopy. This reality offers new diagnostics tools to clinical practice but emphasizes also the lack of multivendor system's interoperability. Without the adoption of standard data formats and communications methods, it will be impossible to build this industry through the installation of vendor-neutral archives and the establishment of telepathology services in the cloud. The DICOM protocol is a feasible solution to the aforementioned problem because it already provides an interface for visible light and whole slide microscope imaging modalities. While some scanners currently have DICOM interfaces, the vast majority of manufacturers continue to use proprietary solutions. This article proposes an automated DICOMization pipeline that can efficiently transform distinct proprietary microscope images from CLSM, FIB-SEM, and WSI scanners into standard DICOM with their biological information maintained within their metadata. The system feasibility and performance were evaluated with fifteen distinct proprietary modalities, including stacked WSI samples. The results demonstrated that the proposed methodology is accurate and can be used in production. The normalized objects were stored through the standard communications in the Dicoogle open-source archive.

Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Cortical and Subcortical Features from MRI T1 Brain Images Utilizing Four Different Types of Datasets.

Alzheimer's disease (AD) is one of the most common neurodegenerative illnesses (dementia) among the elderly. Recently, researchers have developed a new method for the instinctive analysis of AD based on machine learning and its subfield, deep learning. Recent state-of-the-art techniques consider multimodal diagnosis, which has been shown to achieve high accuracy compared to a unimodal prognosis. Furthermore, many studies have used structural magnetic resonance imaging (MRI) to measure brain volumes and the volume of subregions, as well as to search for diffuse changes in white/gray matter in the brain. In this study, T1-weighted structural MRI was used for the early classification of AD. MRI results in high-intensity visible features, making preprocessing and segmentation easy. To use this image modality, we acquired four types of datasets from each dataset's server. In this work, we downloaded 326 subjects from the National Research Center for Dementia homepage, 123 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) homepage, 121 subjects from the Alzheimer's Disease Repository Without Borders homepage, and 131 subjects from the National Alzheimer's Coordinating Center homepage. In our experiment, we used the multiatlas label propagation with expectation-maximization-based refinement segmentation method. We segmented the images into 138 anatomical morphometry images (in which 40 features belonged to subcortical volumes and the remaining 98 features belonged to cortical thickness). The entire dataset was split into a 70 : 30 (training and testing) ratio before classifying the data. A principal component analysis was used for dimensionality reduction. Then, the support vector machine radial basis function classifier was used for classification between two groups-AD versus health control (HC) and early mild cognitive impairment (MCI) (EMCI) versus late MCI (LMCI). The proposed method performed very well for all four types of dataset. For instance, for the AD versus HC group, the classifier achieved an area under curve (AUC) of more than 89% for each dataset. For the EMCI versus LMCI group, the classifier achieved an AUC of more than 80% for every dataset. Moreover, we also calculated Cohen kappa and Jaccard index statistical values for all datasets to evaluate the classification reliability. Finally, we compared our results with those of recently published state-of-the-art methods.

Classification and Graphical Analysis of Alzheimer's Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype.

Graphical, voxel, and region-based analysis has become a popular approach to studying neurodegenerative disorders such as Alzheimer's disease (AD) and its prodromal stage [mild cognitive impairment (MCI)]. These methods have been used previously for classification or discrimination of AD in subjects in a prodromal stage called stable MCI (MCIs), which does not convert to AD but remains stable over a period of time, and converting MCI (MCIc), which converts to AD, but the results reported across similar studies are often inconsistent. Furthermore, the classification accuracy for MCIs vs. MCIc is limited. In this study, we propose combining different neuroimaging modalities (sMRI, FDG-PET, AV45-PET, DTI, and rs-fMRI) with the apolipoprotein-E genotype to form a multimodal system for the discrimination of AD, and to increase the classification accuracy. Initially, we used two well-known analyses to extract features from each neuroimage for the discrimination of AD: whole-brain parcelation analysis (or region-based analysis), and voxel-wise analysis (or voxel-based morphometry). We also investigated graphical analysis (nodal and group) for all six binary classification groups (AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs). Data for a total of 129 subjects (33 AD, 30 MCIs, 31 MCIc, and 35 HCs) for each imaging modality were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) homepage. These data also include two APOE genotype data points for the subjects. Moreover, we used the 2-mm AICHA atlas with the NiftyReg registration toolbox to extract 384 brain regions from each PET (FDG and AV45) and sMRI image. For the rs-fMRI images, we used the DPARSF toolbox in MATLAB for the automatic extraction of data and the results for REHO, ALFF, and fALFF. We also used the pyClusterROI script for the automatic parcelation of each rs-fMRI image into 200 brain regions. For the DTI images, we used the FSL (Version 6.0) toolbox for the extraction of fractional anisotropy (FA) images to calculate a tract-based spatial statistic. Moreover, we used the PANDA toolbox to obtain 50 white-matter-region-parcellated FA images on the basis of the 2-mm JHU-ICBM-labeled template atlas. To integrate the different modalities and different complementary information into one form, and to optimize the classifier, we used the multiple kernel learning (MKL) framework. The obtained results indicated that our multimodal approach yields a significant improvement in accuracy over any single modality alone. The areas under the curve obtained by the proposed method were 97.78, 96.94, 95.56, 96.25, 96.67, and 96.59% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs binary classification, respectively. Our proposed multimodal method improved the classification result for MCIs vs. MCIc groups compared with the unimodal classification results. Our study found that the (left/right) precentral region was present in all six binary classification groups (this region can be considered the most significant region). Furthermore, using nodal network topology, we found that FDG, AV45-PET, and rs-fMRI were the most important neuroimages, and showed many affected regions relative to other modalities. We also compared our results with recently published results.

Prediction and Classification of Alzheimer's Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers.

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

Early diagnosis of Alzheimer's disease using combined features from voxel-based morphometry and cortical, subcortical, and hippocampus regions of MRI T1 brain images.

In recent years, several high-dimensional, accurate, and effective classification methods have been proposed for the automatic discrimination of the subject between Alzheimer's disease (AD) or its prodromal phase {i.e., mild cognitive impairment (MCI)} and healthy control (HC) persons based on T1-weighted structural magnetic resonance imaging (sMRI). These methods emphasis only on using the individual feature from sMRI images for the classification of AD, MCI, and HC subjects and their achieved classification accuracy is low. However, latest multimodal studies have shown that combining multiple features from different sMRI analysis techniques can improve the classification accuracy for these types of subjects. In this paper, we propose a novel classification technique that precisely distinguishes individuals with AD, aAD (stable MCI, who had not converted to AD within a 36-month time period), and mAD (MCI caused by AD, who had converted to AD within a 36-month time period) from HC individuals. The proposed method combines three different features extracted from structural MR (sMR) images using voxel-based morphometry (VBM), hippocampal volume (HV), and cortical and subcortical segmented region techniques. Three classification experiments were performed (AD vs. HC, aAD vs. mAD, and HC vs. mAD) with 326 subjects (171 elderly controls and 81 AD, 35 aAD, and 39 mAD patients). For the development and validation of the proposed classification method, we acquired the sMR images from the dataset of the National Research Center for Dementia (NRCD). A five-fold cross-validation technique was applied to find the optimal hyperparameters for the classifier, and the classification performance was compared by using three well-known classifiers: K-nearest neighbor, support vector machine, and random forest. Overall, the proposed model with the SVM classifier achieved the best performance on the NRCD dataset. For the individual feature, the VBM technique provided the best results followed by the HV technique. However, the use of combined features improved the classification accuracy and predictive power for the early classification of AD compared to the use of individual features. The most stable and reliable classification results were achieved when combining all extracted features. Additionally, to analyze the efficiency of the proposed model, we used the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to compare the classification performance of the proposed model with those of several state-of-the-art methods.

Alzheimer's Disease Diagnosis Based on Cortical and Subcortical Features.

Alzheimer's disease (AD) is a common neurodegenerative disease with an often seen prodromal mild cognitive impairment (MCI) phase, where memory loss is the main complaint progressively worsening with behavior issues and poor self-care. However, not all patients clinically diagnosed with MCI progress to the AD. Currently, several high-dimensional classification techniques have been developed to automatically distinguish among AD, MCI, and healthy control (HC) patients based on T1-weighted MRI. However, these method features are based on wavelets, contourlets, gray-level co-occurrence matrix, etc., rather than using clinical features which helps doctors to understand the pathological mechanism of the AD. In this study, a new approach is proposed using cortical thickness and subcortical volume for distinguishing binary and tertiary classification of the National Research Center for Dementia dataset (NRCD), which consists of 326 subjects. Five classification experiments are performed: binary classification, i.e., AD vs HC, HC vs mAD (MCI due to the AD), and mAD vs aAD (asymptomatic AD), and tertiary classification, i.e., AD vs HC vs mAD and AD vs HC vs aAD using cortical and subcortical features. Datasets were divided in a 70/30 ratio, and later, 70% were used for training and the remaining 30% were used to get an unbiased estimation performance of the suggested methods. For dimensionality reduction purpose, principal component analysis (PCA) was used. After that, the output of PCA was passed to various types of classifiers, namely, softmax, support vector machine (SVM), k-nearest neighbors, and naïve Bayes (NB) to check the performance of the model. Experiments on the NRCD dataset demonstrated that the softmax classifier is best suited for the AD vs HC classification with an F1 score of 99.06, whereas for other groups, the SVM classifier is best suited for the HC vs mAD, mAD vs aAD, and AD vs HC vs mAD classifications with the F1 scores being 99.51, 97.5, and 99.99, respectively. In addition, for the AD vs HC vs aAD classification, NB performed well with an F1 score of 95.88. In addition, to check our proposed model efficiency, we have also used the OASIS dataset for comparing with 9 state-of-the-art methods.