Mild cognitive impairment classification using combined structural and diffusion imaging biomarkers.

Alzheimer's disease is a multifactorial neurodegenerative disorder preceded by a prodromal stage called mild cognitive impairment (MCI). Early diagnosis of MCI is crucial for delaying the progression and optimizing the treatment. In this study we propose a random forest (RF) classifier to distinguish between MCI and healthy control subjects (HC), identifying the most relevant features computed from structural T1-weighted and diffusion-weighted magnetic resonance images (sMRI and DWI), combined with neuro-psychological scores. To train the RF we used a set of 60 subjects (HC = 30, MCI = 30) drawn from the Alzheimer's disease neuroimaging initiative database, while testing with unseen data was carried out on a 23-subjects Mexican cohort (HC = 12, MCI = 11). Features from hippocampus, thalamus and amygdala, for left and right hemispheres were fed to the RF, with the most relevant being previously selected by applying extra trees classifier and the mean decrease in impurity index. All the analyzed brain structures presented changes in sMRI and DWI features for MCI, but those computed from sMRI contribute the most to distinguish from HC. However, sMRI+DWI improves classification performance in training area under the receiver operating characteristic curve (AUROC = 93.5 ± 8%, accuracy = 88.8 ± 9%) and testing with unseen data (AUROC = 93.79%, accuracy = 91.3%), having a better performance when neuro-psychological scores were included. Compared to other classifiers the proposed RF provide the best performance for HC/MCI discrimination and the application of a feature selection step improves its performance. These findings imply that multimodal analysis gives better results than unimodal analysis and hence may be a useful tool to assist in early MCI diagnosis.

Evaluation of Brain Tortuosity Measurement for the Automatic Multimodal Classification of Subjects with Alzheimer's Disease.

The 3D tortuosity determined in several brain areas is proposed as a new morphological biomarker (BM) to be considered in early detection of Alzheimer's disease (AD). It is measured using the sum of angles method and it has proven to be sensitive to anatomical changes that appear in gray and white matter and temporal and parietal lobes during mild cognitive impairment (MCI). Statistical analysis showed significant differences (p < 0.05) between tortuosity indices determined for healthy controls (HC) vs. MCI and HC vs. AD in most of the analyzed structures. Other clinically used BMs have also been incorporated in the analysis: beta-amyloid and tau protein CSF and plasma concentrations, as well as other image-extracted parameters. A classification strategy using random forest (RF) algorithms was implemented to discriminate between three samples of the studied populations, selected from the ADNI database. Classification rates considering only image-extracted parameters show an increase of 9.17%, when tortuosity is incorporated. An enhancement of 1.67% is obtained when BMs measured from several modalities are combined with tortuosity.

Probabilistic Learning Coherent Point Drift for 3D Ultrasound Fetal Head Registration.

Quantification of brain growth is crucial for the assessment of fetal well being, for which ultrasound (US) images are the chosen clinical modality. However, they present artefacts, such as acoustic occlusion, especially after the 18th gestational week, when cranial calcification appears. Fetal US volume registration is useful in one or all of the following cases: to monitor the evolution of fetometry indicators, to segment different structures using a fetal brain atlas, and to align and combine multiple fetal brain acquisitions. This paper presents a new approach for automatic registration of real 3D US fetal brain volumes, volumes that contain a considerable degree of occlusion artefacts, noise, and missing data. To achieve this, a novel variant of the coherent point drift method is proposed. This work employs supervised learning to segment and conform a point cloud automatically and to estimate their subsequent weight factors. These factors are obtained by a random forest-based classification and are used to appropriately assign nonuniform membership probability values of a Gaussian mixture model. These characteristics allow for the automatic registration of 3D US fetal brain volumes with occlusions and multiplicative noise, without needing an initial point cloud. Compared to other intensity and geometry-based algorithms, the proposed method achieves an error reduction of 7.4% to 60.7%, with a target registration error of only 6.38 ± 3.24 mm. This makes the herein proposed approach highly suitable for 3D automatic registration of fetal head US volumes, an approach which can be useful to monitor fetal growth, segment several brain structures, or even compound multiple acquisitions taken from different projections.

Neuroanatomical features and its usefulness in classification of patients with PANDAS.

OBJECTIVE: An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype. METHODS: Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA. RESULTS: The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls. CONCLUSION: The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.

Spatial Compounding of 3-D Fetal Brain Ultrasound Using Probabilistic Maps.

A new method to address the problem of shadowing in fetal brain ultrasound volumes is presented. The proposed approach is based on the spatial composition of multiple 3-D fetal head projections using the weighted Euclidean norm as an operator. A support vector machine, which is trained with optimal textural features, was used to assign weighting according to the posterior probabilities of brain tissue and shadows. Both phantom and real fetal head ultrasound volumes were compounded using previously reported operators and compared with the proposed composition method to validate it. The quantitative evaluations revealed increases in signal-to-noise ratio ≤35% and in contrast-to-noise ratio ≤135% using real data. Qualitative comparisons made by obstetricians indicated that this novel method adequately recovers brain tissue and improves the visibility of the main cerebral structures. This may prove useful both for fetal monitoring and in the diagnosis of brain defects. Overall this new approach outperforms spatial composition methods previously reported.

Neural Modulation in Aversive Emotion Processing: An Independent Component Analysis Study.

Emotional processing has an important role in social interaction. We report the findings about the Independent Component Analysis carried out on a fMRI set obtained with a paradigm of face emotional processing. The results showed that an independent component, mainly cerebellar-medial-frontal, had a positive modulation associated with fear processing. Also, another independent component, mainly parahippocampal-prefrontal, showed a negative modulation that could be associated with implicit reappraisal of emotional stimuli. Independent Component Analysis could serve as a method to understand complex cognitive processes and their underlying neural dynamics.

P300 Detection Based on EEG Shape Features.

We present a novel approach to describe a P300 by a shape-feature vector, which offers several advantages over the feature vector used by the BCI2000 system. Additionally, we present a calibration algorithm that reduces the dimensionality of the shape-feature vector, the number of trials, and the electrodes needed by a Brain Computer Interface to accurately detect P300s; we also define a method to find a template that best represents, for a given electrode, the subject's P300 based on his/her own acquired signals. Our experiments with 21 subjects showed that the SWLDA's performance using our shape-feature vector was 93%, that is, 10% higher than the one obtained with BCI2000-feature's vector. The shape-feature vector is 34-dimensional for every electrode; however, it is possible to significantly reduce its dimensionality while keeping a high sensitivity. The validation of the calibration algorithm showed an averaged area under the ROC (AUROC) curve of 0.88. Also, most of the subjects needed less than 15 trials to have an AUROC superior to 0.8. Finally, we found that the electrode C4 also leads to better classification.

Description and classification of normal and pathological aging processes based on brain magnetic resonance imaging morphology measures.

We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages.

Normality index of ventricular contraction based on a statistical model from FADS.

Radionuclide-based imaging is an alternative to evaluate ventricular function and synchrony and may be used as a tool for the identification of patients that could benefit from cardiac resynchronization therapy (CRT). In a previous work, we used Factor Analysis of Dynamic Structures (FADS) to analyze the contribution and spatial distribution of the 3 most significant factors (3-MSF) present in a dynamic series of equilibrium radionuclide angiography images. In this work, a probability density function model of the 3-MSF extracted from FADS for a control group is presented; also an index, based on the likelihood between the control group's contraction model and a sample of normal subjects is proposed. This normality index was compared with those computed for two cardiopathic populations, satisfying the clinical criteria to be considered as candidates for a CRT. The proposed normality index provides a measure, consistent with the phase analysis currently used in clinical environment, sensitive enough to show contraction differences between normal and abnormal groups, which suggests that it can be related to the degree of severity in the ventricular contraction dyssynchrony, and therefore shows promise as a follow-up procedure for patients under CRT.

Automatic segmentation of the fetal cerebellum on ultrasound volumes, using a 3D statistical shape model.

Previous work has shown that the segmentation of anatomical structures on 3D ultrasound data sets provides an important tool for the assessment of the fetal health. In this work, we present an algorithm based on a 3D statistical shape model to segment the fetal cerebellum on 3D ultrasound volumes. This model is adjusted using an ad hoc objective function which is in turn optimized using the Nelder-Mead simplex algorithm. Our algorithm was tested on ultrasound volumes of the fetal brain taken from 20 pregnant women, between 18 and 24 gestational weeks. An intraclass correlation coefficient of 0.8528 and a mean Dice coefficient of 0.8 between cerebellar volumes measured using manual techniques and the volumes calculated using our algorithm were obtained. As far as we know, this is the first effort to automatically segment fetal intracranial structures on 3D ultrasound data.

Robust nonparametric segmentation of infarct lesion from diffusion-weighted MR images.

Magnetic Resonance Imaging (MRI) is increasingly used for the diagnosis and monitoring of neurological disorders. In particular Diffusion-Weighted MRI (DWI) is highly sensitive in detecting early cerebral ischemic changes in acute stroke. Cerebral infarction lesion segmentation from DWI is accomplished in this work by applying nonparametric density estimation. The quality of the class boundaries is improved by including an edge confidence map, that is the confidence of truly being in the presence of a border between adjacent regions. The adjacency graph, that is constructed with the label regions, is analyzed and pruned to merge adjacent regions. The method was applied to real images, keeping all parameters constant throughout the process for each data set. The combination of region segmentation and edge detection proved to be a robust automatic technique of segmentation from DWI images of cerebral infarction regions in acute ischemic stroke. In a comparison with the reference infarct lesions segmentation, the automatic segmentation presented a significant correlation (r=0.935), and an average Tanimoto index of 0.538.

Data-driven brain MRI segmentation supported on edge confidence and a priori tissue information.

Brain magnetic resonance imaging segmentation is accomplished in this work by applying nonparametric density estimation, using the mean shift algorithm in the joint spatial-range domain. The quality of the class boundaries is improved by including an edge confidence map, that represents the confidence of truly being in the presence of a border between adjacent regions; an adjacency graph is then constructed with the labeled regions, and analyzed and pruned to merge adjacent regions. In order to assign image regions to a cerebral tissue type, a spatial normalization between image data and standard probability maps is carried out, so that for each structure a maximum a posteriori probability criterion is applied. The method was applied to synthetic and real images, keeping all parameters constant throughout the process for each type of data. The combination of region segmentation and edge detection proved to be a robust technique, as adequate clusters were automatically identified, regardless of the noise level and bias. In a comparison with reference segmentations, average Tanimoto indexes of 0.90-0.99 were obtained for synthetic data and of 0.59-0.99 for real data, considering gray matter, white matter, and background.

Analysis of ventricular contraction by factorial phase imaging with equilibrium radionuclide angiography.

Equilibrium radionuclide angiography (ERNA) imaging of the heart is used to visualize and quantify the cardiac function. Phase image analysis has been used for the localization of several conduction and contraction abnormalities and has been proposed to evaluate cardiac resynchronization therapy. The ventricular contraction has been described with indices like mean, standard deviation, mode, synchrony and entropy with Fourier phase imaging (FoPI). Factorial phase imaging (FaPI) has been used for wall motion abnormalities analysis and on a cardiac phantom, but not for synchrony quantification. In this paper a comparison of several indices obtained with FoPI and FaPI for a normal population is presented. These indices were computed inside regions corresponding to left ventricle, right ventricle and the total ventricular area. A set of ERNA images from 23 normal volunteers was analyzed. The comparison of indices was carried out by paired Student's t test with a significance level of (p<0.05). The results show significant differences among FoPI and FaPI on the analysis of ventricular contraction in normal individuals and consequently, on the quantification of the synchrony of contraction. The indices obtained from FaPI can be used to characterize a normal subject population for the evaluation of ventricular contraction synchrony.

Segmenting brain MRI using adaptive mean shift.

To delineate arbitrarily shaped clusters in a complex multimodal feature space, such as the brain MRI intensity space, often requires kernel estimation techniques with locally adaptive bandwidths, such as the adaptive mean shift procedure. Proper selection of the kernel bandwidth is a critical step for a better quality in the clustering. This paper presents a solution for the bandwidth selection, which is completely nonparametric and is based on the sample point estimator to yield a spatial pattern of local bandwidths. The method was applied to synthetic brain images, showing a high performance even in the presence of varying noise level and bias.

Coupling of radial-basis network and active contour model for multispectral brain MRI segmentation.

Magnetic resonance (MR) has been accepted as the reference image study in the clinical environment. The development of new sequences has allowed obtaining diverse images with high clinical importance and whose interpretation requires their joint analysis (multispectral MRI). Recent approaches to segment MRI point toward the definition of hybrid models, where the advantages of region and contour-based methods can be exploited to look for the integration or fusion of information, thus enhancing the performance of the individual approaches. Following this perspective, a hybrid model for multispectral brain MRI segmentation is presented. The model couples a segmenter, based on a radial basis network (RBFNNcc), and an active contour model, based on a cubic spline active contour (CSAC) interpolation. Both static and dynamic coupling of RBFNNcc and CSAC are proposed; the RBFNNcc stage provides an initial contour to the CSAC; the initial contour is optimally sampled with respect to its curvature variations; multispectral information and a restriction term are included into the CSAC energy equation. Segmentations were compared to a reference stack, indicating high-quality performance as measured by Tanimoto indexes of 0.74 +/- 0.08.

The effects of body position, controlled breathing and exercise on the heart rate variability parameters in healthy subjects

Durante la realización de cinco maniobras se determinó el comportamiento de parámetros temporales y espectrales de la variabilidad de la frecuencia cardiaca para caracterizar los niveles de actividad simpático-vagal. Se comparó la capacidad discriminativa de dos formas de obtención de los parámetros espectrales y se evaluó la influencia respiratoria. Fueron analizados 110 archivos de frecuencia cardiaca instantánea y amplitud respiratoriia, obtenidos de 22 sujetos sanos durante 5 maniobras: acostado, respiración controlada, parado, ejercicio y recuperación. Se encontró un comportamiento característico y discriminativo entre las maniobras para los parámetros temporales de dispersión y los componentes de baja parcial e intermedia. Se observó un comportamiento semejante para los componentes espectrales en sus dos formas de integración normalización, resultado que hace independiente la interpretación funcional del procedimiento seleccionado. I a partición del componente de baja en dos, hizo que éstos tuvieran una mayor capacidad discriminativa. La respiración ejerció una influencia importante durante la respiración controlada y moderada en el resto de las maniobras. En conclusión las maniobras determinaron un comportamiento tipico en los parámetros de dispersión y espectrales (componentes de baja parcial e intermedia), los cuales indicaron en forma adecuada niveles distintivos en la actividad simpático-vagal para cada una de ellas