Hierarchical segmentation-assisted multimodal registration for MR brain images

Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assisted similarity metric based on point-wise mutual information (PMI). This similarity metric, termed SPMI, enhances the registration accuracy by considering tissue classification probabilities as prior information, which is generated from an expectation maximization (EM) algorithm. Diffeomorphic demons is then adopted as the registration model and is optimized in a hierarchical framework (H-SPMI) based on different levels of anatomical structure as prior knowledge. The proposed method is evaluated using Brainweb synthetic data and clinical fMRI images. Both qualitative and quantitative assessment were performed as well as a sensitivity analysis to the segmentation error. Compared to the pure intensity-based approaches which only maximize mutual information, we show that the proposed algorithm provides significantly better accuracy on both synthetic and clinical data.

Statistical model-based segmentation of the proximal femur in digital antero-posterior (AP) pelvic radiographs.

PURPOSE    Segmentation of the proximal femur in digital antero-posterior (AP) pelvic radiographs is required to create a three-dimensional model of the hip joint for use in planning and treatment. However, manually extracting the femoral contour is tedious and prone to subjective bias, while automatic segmentation must accommodate poor image quality, anatomical structure overlap, and femur deformity. A new method was developed for femur segmentation in AP pelvic radiographs. METHODS    Using manual annotations on 100 AP pelvic radiographs, a statistical shape model (SSM) and a statistical appearance model (SAM) of the femur contour were constructed. The SSM and SAM were used to segment new AP pelvic radiographs with a three-stage approach. At initialization, the mean SSM model is coarsely registered to the femur in the AP radiograph through a scaled rigid registration. Mahalanobis distance defined on the SAM is employed as the search criteria for each annotated suggested landmark location. Dynamic programming was used to eliminate ambiguities. After all landmarks are assigned, a regularized non-rigid registration method deforms the current mean shape of SSM to produce a new segmentation of proximal femur. The second and third stages are iteratively executed to convergence. RESULTS    A set of 100 clinical AP pelvic radiographs (not used for training) were evaluated. The mean segmentation error was [Formula: see text], requiring [Formula: see text] s per case when implemented with Matlab. The influence of the initialization on segmentation results was tested by six clinicians, demonstrating no significance difference. CONCLUSIONS    A fast, robust and accurate method for femur segmentation in digital AP pelvic radiographs was developed by combining SSM and SAM with dynamic programming. This method can be extended to segmentation of other bony structures such as the pelvis.

Die Untersuchung der Schulter in der Praxis

Liegt die Ursache von Schmerzen oder Funktionseinbussen im Schulterbereich selbst, können diese mit einer präzisen klinischen Untersuchung in den meisten Fällen einer bestimmten anatomischen Struktur zugeordnet werden. Vorwiegend im Bild, mit nur knappem Text, werden die einzelnen Tests dargestellt. Dabei wurde zur besseren Merkfähigkeit die jeweils getestete Struktur mit eingezeichnet. Auch die häufigsten in der Praxis vorkommenden Trigger-Punkte mit der entsprechenden pseudoradikulären Symptomatik werden dargestellt. Ziel dieses Artikels ist die Erleichterung der täglichen Arbeit in der Praxis bei häufigen Schulterproblemen.

Articulated Statistical Shape Model-Based 2D-3D Reconstruction of a Hip Joint

In this paper, reconstruction of three-dimensional (3D) patient-specific models of a hip joint from two-dimensional (2D) calibrated X-ray images is addressed. Existing 2D-3D reconstruction techniques usually reconstruct a patient-specific model of a single anatomical structure without considering the relationship to its neighboring structures. Thus, when those techniques would be applied to reconstruction of patient-specific models of a hip joint, the reconstructed models may penetrate each other due to narrowness of the hip joint space and hence do not represent a true hip joint of the patient. To address this problem we propose a novel 2D-3D reconstruction framework using an articulated statistical shape model (aSSM). Different from previous work on constructing an aSSM, where the joint posture is modeled as articulation in a training set via statistical analysis, here it is modeled as a parametrized rotation of the femur around the joint center. The exact rotation of the hip joint as well as the patient-specific models of the joint structures, i.e., the proximal femur and the pelvis, are then estimated by optimally fitting the aSSM to a limited number of calibrated X-ray images. Taking models segmented from CT data as the ground truth, we conducted validation experiments on both plastic and cadaveric bones. Qualitatively, the experimental results demonstrated that the proposed 2D-3D reconstruction framework preserved the hip joint structure and no model penetration was found. Quantitatively, average reconstruction errors of 1.9 mm and 1.1 mm were found for the pelvis and the proximal femur, respectively.

Anatomia ecológica do lenho de espécies arbustivas e arbóreas que ocorrem naturalmente em bosques com drástico gradiente de precipitação ao Noroeste da Patagônia, Argentina

A utilização de gradientes ambientais no estudo de comunidades vegetais possibilita a eleição de sítios onde há a predominância de um fator abiótico que determina o sucesso ou o fracasso de espécies ao longo de sua extensão. Entre as inúmeras ferramentas utilizadas no estudo de gradientes climáticos, se destaca a anatomia do lenho, pois, é um ramo da ciência que permite analisar, além dos aspectos espaciais, os aspectos temporais dos sítios por meio dos anéis de crescimento. Além disso, a ampla distribuição das plantas lenhosas ao longo do globo possibilita análises em praticamente todos os tipos de biomas e ecossistemas terrestres. Dentro desse contexto estão os bosques andino-patagônicos de Araucaria araucana (Pehuén) ao norte de sua distribuição na Argentina. Esses bosques ocupam territórios caracterizados por um acentuado gradiente de precipitação, que vai de cerca de 3000 a 100 milímetros anuais, entre a cordilheira do Andes e a estepe patagônica, que os define como bosques mésicos e xéricos, com diferenças ecológicas que condicionam a formação vegetal, dinâmica, estrutura, relações com o clima e vulnerabilidade em cenários de mudanças ambientais. O objetivo do projeto foi descrever e analisar comparativamente a estrutura anatômica do lenho de 33 espécies arbóreas e arbustivas ocorrentes ao longo de um gradiente de precipitação, entre a encosta da cordilheira dos Andes e a estepe Patagônica, para verificar possíveis alterações anatômicas que permitam a determinação de tendências e elucidem os limites de distribuição das espécies. Foram coletadas amostras não destrutivas de lenho durante três expedições para a Patagônia entre 2012 e 2014, seguidas de procedimentos laboratoriais de confeccção de lâminas histológicas, preparo de amostras para análises dendrocronológicas, captura de imagens com câmeras acopladas a microscópios óptico e eletrônico de varredura, mensurações, descrições e análises comparativas com o auxílio de softwares. Foram identificados caracteres anatômicos exclusivos de sítios secos e úmidos que permitiram a caracterização, posicionamento ao longo do gradiente de precipitação e grupamento de espécies xerófitas e mesófitas; A ultra-estrutura das pontoações de traqueídeos de Araucaria araucana apresentou diferenças marcantes na frequência e porosidade de suas membranas, sendo maior e menos porosas em sítios xéricos, e menor e mais porosas nos mésicos; a chave dicotômica microscópica permitiu a identificação das 32 espécies arbustivas, as espécies Chuquiraga oppositifolia e Nothofagus antarctica apresentaram potencial dendrocronológico, e foram identificadas tendências anatômicas latitudinais influenciadas pelo clima nos extremos da América do Sul. A anatomia do lenho se mostrou uma ferramenta confiável no estudo de um gradiente de precipitação na Patagônia argentina, e os resultados apontam para riscos de embolismos e morte induzida por falha no sistema hidráulico de Araucaria araucana ao longo de todo o gradiente, em função do atual cenário climático, e suas projeções em médio e longo prazos.

Simulation of Brugada syndrome using cellular and three-dimensional whole-heart modeling approaches

Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

Causality and synchronisation in complex systems with applications to neuroscience

This thesis presents an investigation, of synchronisation and causality, motivated by problems in computational neuroscience. The thesis addresses both theoretical and practical signal processing issues regarding the estimation of interdependence from a set of multivariate data generated by a complex underlying dynamical system. This topic is driven by a series of problems in neuroscience, which represents the principal background motive behind the material in this work. The underlying system is the human brain and the generative process of the data is based on modern electromagnetic neuroimaging methods . In this thesis, the underlying functional of the brain mechanisms are derived from the recent mathematical formalism of dynamical systems in complex networks. This is justified principally on the grounds of the complex hierarchical and multiscale nature of the brain and it offers new methods of analysis to model its emergent phenomena. A fundamental approach to study the neural activity is to investigate the connectivity pattern developed by the brain’s complex network. Three types of connectivity are important to study: 1) anatomical connectivity refering to the physical links forming the topology of the brain network; 2) effective connectivity concerning with the way the neural elements communicate with each other using the brain’s anatomical structure, through phenomena of synchronisation and information transfer; 3) functional connectivity, presenting an epistemic concept which alludes to the interdependence between data measured from the brain network. The main contribution of this thesis is to present, apply and discuss novel algorithms of functional connectivities, which are designed to extract different specific aspects of interaction between the underlying generators of the data. Firstly, a univariate statistic is developed to allow for indirect assessment of synchronisation in the local network from a single time series. This approach is useful in inferring the coupling as in a local cortical area as observed by a single measurement electrode. Secondly, different existing methods of phase synchronisation are considered from the perspective of experimental data analysis and inference of coupling from observed data. These methods are designed to address the estimation of medium to long range connectivity and their differences are particularly relevant in the context of volume conduction, that is known to produce spurious detections of connectivity. Finally, an asymmetric temporal metric is introduced in order to detect the direction of the coupling between different regions of the brain. The method developed in this thesis is based on a machine learning extensions of the well known concept of Granger causality. The thesis discussion is developed alongside examples of synthetic and experimental real data. The synthetic data are simulations of complex dynamical systems with the intention to mimic the behaviour of simple cortical neural assemblies. They are helpful to test the techniques developed in this thesis. The real datasets are provided to illustrate the problem of brain connectivity in the case of important neurological disorders such as Epilepsy and Parkinson’s disease. The methods of functional connectivity in this thesis are applied to intracranial EEG recordings in order to extract features, which characterize underlying spatiotemporal dynamics before during and after an epileptic seizure and predict seizure location and onset prior to conventional electrographic signs. The methodology is also applied to a MEG dataset containing healthy, Parkinson’s and dementia subjects with the scope of distinguishing patterns of pathological from physiological connectivity.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Development of a simple and fast “DNA extraction kit” for sea food identification and marine species

Seafood products fraud, the misrepresentation of them, have been discovered all around the world in different forms as false labeling, species substitution, short-weighting or over glazing in order to hide the correct identity, origin or weight of the seafood products. Due to the value of seafood products such as canned tuna, swordfish or grouper, these species are the subject of the commercial fraud is mainly there placement of valuable species with other little or no value species. A similar situation occurs with the shelled shrimp or shellfish that are reduced into pieces for the commercialization. Food fraud by species substitution is an emerging risk given the increasingly global food supply chain and the potential food safety issues. Economic food fraud is committed when food is deliberately placed on the market, for financial gain deceiving consumers (Woolfe, M. & Primrose, S. 2004). As a result of the increased demand and the globalization of the seafood supply, more fish species are encountered in the market. In this scenary, it becomes essential to unequivocally identify the species. The traditional taxonomy, based primarily on identification keys of species, has shown a number of limitations in the use of the distinctive features in many animal taxa, amplified when fish, crustacean or shellfish are commercially transformed. Many fish species show a similar texture, thus the certification of fish products is particularly important when fishes have undergone procedures which affect the overall anatomical structure, such as heading, slicing or filleting (Marko et al., 2004). The absence of morphological traits, a main characteristic usually used to identify animal species, represents a challenge and molecular identification methods are required. Among them, DNA-based methods are more frequently employed for food authentication (Lockley & Bardsley, 2000). In addition to food authentication and traceability, studies of taxonomy, population and conservation genetics as well as analysis of dietary habits and prey selection, also rely on genetic analyses including the DNA barcoding technology (Arroyave & Stiassny, 2014; Galimberti et al., 2013; Mafra, Ferreira, & Oliveira, 2008; Nicolé et al., 2012; Rasmussen & Morrissey, 2008), consisting in PCR amplification and sequencing of a COI mitochondrial gene specific region. The system proposed by P. Hebert et al. (2003) locates inside the mitochondrial COI gene (cytochrome oxidase subunit I) the bioidentification system useful in taxonomic identification of species (Lo Brutto et al., 2007). The COI region, used for genetic identification - DNA barcode - is short enough to allow, with the current technology, to decode sequence (the pairs of nucleotide bases) in a single step. Despite, this region only represents a tiny fraction of the mitochondrial DNA content in each cell, the COI region has sufficient variability to distinguish the majority of species among them (Biondo et al. 2016). This technique has been already employed to address the demand of assessing the actual identity and/or provenance of marketed products, as well as to unmask mislabelling and fraudulent substitutions, difficult to detect especially in manufactured seafood (Barbuto et al., 2010; Galimberti et al., 2013; Filonzi, Chiesa, Vaghi, & Nonnis Marzano, 2010). Nowadays,the research concerns the use of genetic markers to identify not only the species and/or varieties of fish, but also to identify molecular characters able to trace the origin and to provide an effective control tool forproducers and consumers as a supply chain in agreementwith local regulations.

A study of computational methods to analyze gene expression data

The recent advent of new technologies has led to huge amounts of genomic data. With these data come new opportunities to understand biological cellular processes underlying hidden regulation mechanisms and to identify disease related biomarkers for informative diagnostics. However, extracting biological insights from the immense amounts of genomic data is a challenging task. Therefore, effective and efficient computational techniques are needed to analyze and interpret genomic data. In this thesis, novel computational methods are proposed to address such challenges: a Bayesian mixture model, an extended Bayesian mixture model, and an Eigen-brain approach. The Bayesian mixture framework involves integration of the Bayesian network and the Gaussian mixture model. Based on the proposed framework and its conjunction with K-means clustering and principal component analysis (PCA), biological insights are derived such as context specific/dependent relationships and nested structures within microarray where biological replicates are encapsulated. The Bayesian mixture framework is then extended to explore posterior distributions of network space by incorporating a Markov chain Monte Carlo (MCMC) model. The extended Bayesian mixture model summarizes the sampled network structures by extracting biologically meaningful features. Finally, an Eigen-brain approach is proposed to analyze in situ hybridization data for the identification of the cell-type specific genes, which can be useful for informative blood diagnostics. Computational results with region-based clustering reveals the critical evidence for the consistency with brain anatomical structure.

Technologies for Anatomical and Geometric Characterization of the Corneal Structure and Anterior Segment: A Review

Corneal and anterior segment imaging techniques have become a crucial tool in the clinical practice of ophthalmology, with a great variety of applications, such as corneal curvature and pachymetric analysis, detection of ectatic corneal conditions, anatomical study of the anterior segment prior to phakic intraocular lens implantation, or densitometric analysis of the crystalline lens. From the Placido-based systems that allow only a characterization of the geometry of the anterior corneal surface to the Scheimpflug photography-based systems that provide a characterization of the cornea, anterior chamber, and crystalline lens, there is a great variety of devices with the capability of analyzing different anatomical parameters with very high precision. To date, Scheimpflug photography-based systems are the devices providing the more complete analysis of the anterior segment in a non-invasive way. More developments are required in anterior segment imaging technologies in order to improve the analysis of the crystalline lens structure as well as the ocular structures behind the iris in a non-invasive way when the pupil is not dilated.

The anatomical remembrancer, or, Complete pocket anatomist: containing a concise description of the structure of the human body.

Mode of access: Internet.

Anatomical investigations : comprising descriptions of various fasciae of the human body : the discoveries of the manner in which the pericardium is formed from the superficial fascia : the capsular ligament of the shoulder joint from the brachial fascia : and the capsular ligament of the hip joint from the fascia lata : to which is added an account of some irregularities of structure and morbid anatomy : with a description of a new anatomical table /

Includes A treatise on the minute anatomy of the bones, by Antonio Scarpa; transl. by J.D. Godman.

Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.