Identifying potential gene biomarkers for Parkinson's disease through an information entropy based approach.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease and represents the most common disease of this type, after Alzheimer's dementia. It is characterized by motor and nonmotor features and by a long prodromal stage that lasts many years. Genetic research has shown that PD is a complex and multisystem disorder. To capture the molecular complexity of this disease we used a complex network approach. We maximized the information entropy of the gene co-expression matrix betweenness to obtain a gene adjacency matrix; then we used a fast greedy algorithm to detect communities. Finally we applied principal component analysis on the detected gene communities, with the ultimate purpose of discriminating between PD patients and healthy controls by means of a random forests classifier. We used a publicly available substantia nigra microarray dataset, GSE20163, from NCBI GEO database, containing gene expression profiles for 10 PD patients and 18 normal controls. With this methodology we identified two gene communities that discriminated between the two groups with mean accuracy of 0.88 ± 0.03 and 0.84 ± 0.03, respectively, and validated our results on an independent microarray experiment. The two gene communities presented a considerable reduction in size, over 100 times, compared to the initial network and were stable within a range of tested parameters. Further research focusing on the restricted number of genes belonging to the selected communities may reveal essential mechanisms responsible for PD at a network level and could contribute to the discovery of new biomarkers for PD.

Microcalcification detection in full-field digital mammograms: A fully automated computer-aided system.

BACKGROUND: Microcalcification clusters in mammograms can be considered as early signs of breast cancer. However, their detection is a very challenging task because of different factors: large variety of breast composition, highly textured breast anatomy, impalpable size of microcalcifications in some cases, as well as inherent low contrast of mammograms. Thus, the need to support the clinicians' work with an automatic tool. METHODS: In this work a three-phases approach for clustered microcalcification detection is presented. Specifically, it is made up of a pre-processing step, aimed at highlighting potentially interesting breast structures, followed by a single microcalcification detection step, based on Hough transform, that is able to grasp the innate characteristic shape of the structures of interest. Finally, a cluster identification step to group microcalcifications is carried out by means of a clustering algorithm able to codify expert domain rules. RESULTS: The detection performance of the proposed method has been evaluated on 364 mammograms of 182 patients obtaining a true positive ratio of 91.78% with 2.87 false positives per image. CONCLUSIONS: Experimental results demonstrated that the proposed method is able to detect microcalcification clusters in digital mammograms showing performance comparable to different methodologies exploited in the state-of-art approaches, with the advantage that it does not require any training phase and a large set of data. The performance of the proposed approach remains high even for more difficult clinical cases of mammograms of young women having high-density breast tissue thus resulting in a reduced contrast between microcalcifications and surrounding dense tissues.

A Gradient-Based Approach for Breast DCE-MRI Analysis.

Breast cancer is the main cause of female malignancy worldwide. Effective early detection by imaging studies remains critical to decrease mortality rates, particularly in women at high risk for developing breast cancer. Breast Magnetic Resonance Imaging (MRI) is a common diagnostic tool in the management of breast diseases, especially for high-risk women. However, during this examination, both normal and abnormal breast tissues enhance after contrast material administration. Specifically, the normal breast tissue enhancement is known as background parenchymal enhancement: it may represent breast activity and depends on several factors, varying in degree and distribution in different patients as well as in the same patient over time. While a light degree of normal breast tissue enhancement generally causes no interpretative difficulties, a higher degree may cause difficulty to detect and classify breast lesions at Magnetic Resonance Imaging even for experienced radiologists. In this work, we intend to investigate the exploitation of some statistical measurements to automatically characterize the enhancement trend of the whole breast area in both normal and abnormal tissues independently from the presence of a background parenchymal enhancement thus to provide a diagnostic support tool for radiologists in the MRI analysis.

Trial latencies estimation of event-related potentials in EEG by means of genetic algorithms.

OBJECTIVE: Event-related potentials (ERPs) are usually obtained by averaging thus neglecting the trial-to-trial latency variability in cognitive electroencephalography (EEG) responses. As a consequence the shape and the peak amplitude of the averaged ERP are smeared and reduced, respectively, when the single-trial latencies show a relevant variability. To date, the majority of the methodologies for single-trial latencies inference are iterative schemes providing suboptimal solutions, the most commonly used being the Woody's algorithm. APPROACH: In this study, a global approach is developed by introducing a fitness function whose global maximum corresponds to the set of latencies which renders the trial signals most aligned as possible. A suitable genetic algorithm has been implemented to solve the optimization problem, characterized by new genetic operators tailored to the present problem. MAIN RESULTS: The results, on simulated trials, showed that the proposed algorithm performs better than Woody's algorithm in all conditions, at the cost of an increased computational complexity (justified by the improved quality of the solution). Application of the proposed approach on real data trials, resulted in an increased correlation between latencies and reaction times w.r.t. the output from RIDE method. SIGNIFICANCE: The above mentioned results on simulated and real data indicate that the proposed method, providing a better estimate of single-trial latencies, will open the way to more accurate study of neural responses as well as to the issue of relating the variability of latencies to the proper cognitive and behavioural correlates.

Hybrid x-space: a new approach for MPI reconstruction.

Magnetic particle imaging (MPI) is a new medical imaging technique capable of recovering the distribution of superparamagnetic particles from their measured induced signals. In literature there are two main MPI reconstruction techniques: measurement-based (MB) and x-space (XS). The MB method is expensive because it requires a long calibration procedure as well as a reconstruction phase that can be numerically costly. On the other side, the XS method is simpler than MB but the exact knowledge of the field free point (FFP) motion is essential for its implementation. Our simulation work focuses on the implementation of a new approach for MPI reconstruction: it is called hybrid x-space (HXS), representing a combination of the previous methods. Specifically, our approach is based on XS reconstruction because it requires the knowledge of the FFP position and velocity at each time instant. The difference with respect to the original XS formulation is how the FFP velocity is computed: we estimate it from the experimental measurements of the calibration scans, typical of the MB approach. Moreover, a compressive sensing technique is applied in order to reduce the calibration time, setting a fewer number of sampling positions. Simulations highlight that HXS and XS methods give similar results. Furthermore, an appropriate use of compressive sensing is crucial for obtaining a good balance between time reduction and reconstructed image quality. Our proposal is suitable for open geometry configurations of human size devices, where incidental factors could make the currents, the fields and the FFP trajectory irregular.

Hippocampal unified multi-atlas network (HUMAN): protocol and scale validation of a novel segmentation tool.

In this study we present a novel fully automated Hippocampal Unified Multi-Atlas-Networks (HUMAN) algorithm for the segmentation of the hippocampus in structural magnetic resonance imaging. In multi-atlas approaches atlas selection is of crucial importance for the accuracy of the segmentation. Here we present an optimized method based on the definition of a small peri-hippocampal region to target the atlas learning with linear and non-linear embedded manifolds. All atlases were co-registered to a data driven template resulting in a computationally efficient method that requires only one test registration. The optimal atlases identified were used to train dedicated artificial neural networks whose labels were then propagated and fused to obtain the final segmentation. To quantify data heterogeneity and protocol inherent effects, HUMAN was tested on two independent data sets provided by the Alzheimer's Disease Neuroimaging Initiative and the Open Access Series of Imaging Studies. HUMAN is accurate and achieves state-of-the-art performance (Dice[Formula: see text] and Dice[Formula: see text]). It is also a robust method that remains stable when applied to the whole hippocampus or to sub-regions (patches). HUMAN also compares favorably with a basic multi-atlas approach and a benchmark segmentation tool such as FreeSurfer.

Multiple RF classifier for the hippocampus segmentation: Method and validation on EADC-ADNI Harmonized Hippocampal Protocol.

The hippocampus has a key role in a number of neurodegenerative diseases, such as Alzheimer's Disease. Here we present a novel method for the automated segmentation of the hippocampus from structural magnetic resonance images (MRI), based on a combination of multiple classifiers. The method is validated on a cohort of 50 T1 MRI scans, comprehending healthy control, mild cognitive impairment, and Alzheimer's Disease subjects. The preliminary release of the EADC-ADNI Harmonized Protocol training labels is used as gold standard. The fully automated pipeline consists of a registration using an affine transformation, the extraction of a local bounding box, and the classification of each voxel in two classes (background and hippocampus). The classification is performed slice-by-slice along each of the three orthogonal directions of the 3D-MRI using a Random Forest (RF) classifier, followed by a fusion of the three full segmentations. Dice coefficients obtained by multiple RF (0.87 ± 0.03) are larger than those obtained by a single monolithic RF applied to the entire bounding box, and are comparable to state-of-the-art. A test on an external cohort of 50 T1 MRI scans shows that the presented method is robust and reliable. Additionally, a comparison of local changes in the morphology of the hippocampi between the three subject groups is performed. Our work showed that a multiple classification approach can be implemented for the segmentation for the measurement of volume and shape changes of the hippocampus with diagnostic purposes.

Automated voxel-by-voxel tissue classification for hippocampal segmentation: methods and validation.

The hippocampus is an important structural biomarker for Alzheimer's disease (AD) and has a primary role in the pathogenesis of other neurological and psychiatric diseases. This study presents a fully automated pattern recognition system for an accurate and reproducible segmentation of the hippocampus in structural Magnetic Resonance Imaging (MRI). The method was validated on a mixed cohort of 56 T1-weighted structural brain images, and consists of three processing levels: (a) Linear registration: all brain images were registered to a standard template and an automated method was applied to capture the global shape of the hippocampus. (b) Feature extraction: all voxels included in the previously selected volume were characterized by 315 features computed from local information. (c) Voxel classification: a Random Forest algorithm was used to classify voxels as belonging or not belonging to the hippocampus. In order to improve the classification performance, an adaptive learning method based on the use of the Pearson's correlation coefficient was developed. The segmentation results (Dice similarity index = 0.81 ± 0.03) compare well with other state-of-the art approaches. A validation study was conducted on an independent dataset of 100 T1-weighted brain images, achieving significantly better results than those obtained with FreeSurfer.

Post-detection analysis for grating-based ultra-small angle X-ray scattering.

Until recently, the hard X-ray, phase-sensitive imaging technique called grating interferometry was thought to provide information only in real space. However, by utilizing an alternative approach to data analysis we demonstrated that the angular resolved ultra-small angle X-ray scattering distribution can be retrieved from experimental data. Thus, reciprocal space information is accessible by grating interferometry in addition to real space. Naturally, the quality of the retrieved data strongly depends on the performance of the employed analysis procedure, which involves deconvolution of periodic and noisy data in this context. The aim of this article is to compare several deconvolution algorithms to retrieve the ultra-small angle X-ray scattering distribution in grating interferometry. We quantitatively compare the performance of three deconvolution procedures (i.e., Wiener, iterative Wiener and Lucy-Richardson) in case of realistically modeled, noisy and periodic input data. The simulations showed that the algorithm of Lucy-Richardson is the more reliable and more efficient as a function of the characteristics of the signals in the given context. The availability of a reliable data analysis procedure is essential for future developments in grating interferometry.

Pleural nodule identification in low-dose and thin-slice lung computed tomography.

A completely automated system for the identification of pleural nodules in low-dose and thin-slice computed tomography (CT) of the lung has been developed. The directional-gradient concentration method has been applied to the pleura surface and combined with a morphological opening-based procedure to generate a list of nodule candidates. Each nodule candidate is characterized by 12 morphological and textural features, which are analyzed by a rule-based filter and a neural classifier. This detection system has been developed and validated on a dataset of 42 annotated CT scans. The k-fold cross validation has been used to evaluate the neural classifier performance. The system performance variability due to different ground truth agreement levels is discussed. In particular, the poor 44% sensitivity obtained on the ground truth with agreement level 1 (nodules annotated by only one radiologist) with six FP per scan grows up to the 72% if the underlying ground truth is changed to the agreement level 2 (nodules annotated by two radiologists).

MAGIC-5: an Italian mammographic database of digitised images for research.

The implementation of a database of digitised mammograms is discussed. The digitised images were collected beginning in 1999 by a community of physicists in collaboration with radiologists in several Italian hospitals as a first step in developing and implementing a computer-aided detection (CAD) system. All 3,369 mammograms were collected from 967 patients and classified according to lesion type and morphology, breast tissue and pathology type. A dedicated graphical user interface was developed to visualise and process mammograms to support the medical diagnosis directly on a high-resolution screen. The database has been the starting point for developing other medical imaging applications, such as a breast CAD, currently being upgraded and optimised for use in a distributed environment with grid services, in the framework of the Instituto Nazionale di Fisicia Nucleare (INFN)-funded Medical Applications on a Grid Infrastructure Connection (MAGIC)-5 project.

A CAD system for nodule detection in low-dose lung CTs based on region growing and a new active contour model.

A computer-aided detection (CAD) system for the selection of lung nodules in computer tomography (CT) images is presented. The system is based on region growing (RG) algorithms and a new active contour model (ACM), implementing a local convex hull, able to draw the correct contour of the lung parenchyma and to include the pleural nodules. The CAD consists of three steps: (1) the lung parenchymal volume is segmented by means of a RG algorithm; the pleural nodules are included through the new ACM technique; (2) a RG algorithm is iteratively applied to the previously segmented volume in order to detect the candidate nodules; (3) a double-threshold cut and a neural network are applied to reduce the false positives (FPs). After having set the parameters on a clinical CT, the system works on whole scans, without the need for any manual selection. The CT database was recorded at the Pisa center of the ITALUNG-CT trial, the first Italian randomized controlled trial for the screening of the lung cancer. The detection rate of the system is 88.5% with 6.6 FPs/CT on 15 CT scans (about 4700 sectional images) with 26 nodules: 15 internal and 11 pleural. A reduction to 2.47 FPs/CT is achieved at 80% efficiency.

A completely automated CAD system for mass detection in a large mammographic database.

Mass localization plays a crucial role in computer-aided detection (CAD) systems for the classification of suspicious regions in mammograms. In this article we present a completely automated classification system for the detection of masses in digitized mammographic images. The tool system we discuss consists in three processing levels: (a) Image segmentation for the localization of regions of interest (ROIs). This step relies on an iterative dynamical threshold algorithm able to select iso-intensity closed contours around gray level maxima of the mammogram. (b) ROI characterization by means of textural features computed from the gray tone spatial dependence matrix (GTSDM), containing second-order spatial statistics information on the pixel gray level intensity. As the images under study were recorded in different centers and with different machine settings, eight GTSDM features were selected so as to be invariant under monotonic transformation. In this way, the images do not need to be normalized, as the adopted features depend on the texture only, rather than on the gray tone levels, too. (c) ROI classification by means of a neural network, with supervision provided by the radiologist's diagnosis. The CAD system was evaluated on a large database of 3369 mammographic images [2307 negative, 1062 pathological (or positive), containing at least one confirmed mass, as diagnosed by an expert radiologist]. To assess the performance of the system, receiver operating characteristic (ROC) and free-response ROC analysis were employed. The area under the ROC curve was found to be Az = 0.783 +/- 0.008 for the ROI-based classification. When evaluating the accuracy of the CAD against the radiologist-drawn boundaries, 4.23 false positives per image are found at 80% of mass sensitivity.

GPCALMA: a Grid-based tool for mammographic screening.

OBJECTIVES: The next generation of high energy physics (HEP) experiments requires a GRID approach to a distributed computing system: the key concept is the Virtual ORGANISATION (VO), a group of distributed users with a common goal and the will to share their resources. METHODS: A similar approach, applied to a group of hospitals that joined the GPCALMA project (Grid Platform for Computer Assisted Library for MAmmography), will allow common screening programs for early diagnosis of breast and, in the future, lung cancer. The application code makes use of neural networks for the image analysis and is useful in improving the radiologists' diagnostic performance. GRID services allow remote image analysis and interactive online diagnosis, with a potential for a relevant reduction of the delays presently associated with screening programs. RESULTS AND CONCLUSIONS: A prototype of the system, based on AliEn GRID Services [1], is already available, with a central server running common services [2] and several clients connecting to it. Mammograms can be acquired in any location; the related information required to select and access them at any time is stored in a common service called Data Catalogue, which can be queried by any client. Thanks to the PROOF facility [3], the result of a query can be used as input for analysis algorithms, which are executed on the nodes where the input images are stored,. The selected approach avoids data transfers for all the images with a negative diagnosis and allows an almost real time diagnosis for the set of images with high cancer probability.

Direct analysis of molybdenum target generated x-ray spectra with a portable device.

In routine applications, information about the photon flux of x-ray tubes is obtained from exposure measurements and cataloged spectra. This approach relies mainly on the assumption that the real spectrum is correctly approximated by the cataloged one, once the main characteristics of the tube such as voltage, target material, anode angle, and filters are taken account of. In practice, all this information is not always available. Moreover, x-ray tubes with the same characteristics may have different spectra. We describe an apparatus that should be useful for quality control in hospitals and for characterizing new radiographic systems. The apparatus analyzes the spectrum generated by an x-ray mammographic unit. It is based on a commercial CZT produced by AMPTEK Inc. and a set of tungsten collimator disks. The electronics of the CZT are modified so as to obtain a faster response. The signal is digitized using an analog to digital converter with a sampling frequency of up to 20 MHz. The whole signal produced by the x-ray tube is acquired and analyzed off-line in order to accurately recognize pile-up events and reconstruct the emitted spectrum. The energy resolution has been determined using a calibrated x-ray source. Spectra were validated by comparison of the HVL measured using an ionization chamber.