Hiperparatiroidismo primário em doentes jovens

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

(Table T1) Gas hydrate fabric and dipping angles of ODP Leg 204 sediments

The sediments of Hydrate Ridge/Cascadia margin contain extensive amounts of gas hydrate. A total of 57 sediment samples including gas hydrate were preserved in liquid nitrogen and have been imaged using computerized tomography to visualize hydrate distribution and shape. The analysis gives evidence that gas hydrate in vein and veinlet structures is the predominant shape in the deeper gas hydrate stability zone with dipping angles from 30° to 90°(vertical).

Morphometric measurements throughout ontogeny of selected planktic foraminiferal test species

Development plays an important part in shaping adult morphology and morphological disparity, yet its influence on evolutionary processes is seldom explored because of a lack of preservation of ontogenetic stages in the fossil record. By preserving their entire ontogenetic history within their test, and with the advent of high-resolution imaging techniques, planktic foraminifera allow us to investigate the influence of developmental constraints on disparity. Using Synchrotron radiation X-ray tomographic microscopy (SRXTM), we reconstruct the ontogenetic progression of seven species across several of the major morphotypic groups of planktic foraminifera, including morphotypes of a species exhibiting high phenotypic plasticity and closely related pseudo-cryptic sister-taxa. We show differences in growth patterns between the globigerinid species, which appear more tightly regulated within the framework of isometry from the neanic stage, and the globorotaliid species, whose adult stages present allometric trends. Morphological change through ontogeny results in a change in surface area to volume ratios. Different metabolic processes therefore dominate at different stages of ontogeny, changing the vulnerability of the organism to environmental influences over growth, from factors affecting diffusion rates in the juvenile to those affecting energy supply in the adult. These findings identify some of the parameters within which evolutionary mechanisms have to act.

W/O microemulsions for ocular delivery: Evaluation of ocular irritation and precorneal retention

Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were formulated using Crodarnol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as cosurfactant and water. The hypothesis that phase-transition of ME to LC may be induced by tears and serve to prolong precomeal retention was tested. The ocular irritation potential of components and formulations was assessed using a modified hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of selected formulations was investigated in rabbit eye using gamma scintigraphy. Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant. However, all other cosurfactants investigated were irritant and their irritation was dependent on their carbon chain length. A w/o ME formulated without cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was used as the aqueous phase. Precorneal clearance studies revealed that the retention of colloidal and coarse dispersed systems was significantly greater than an aqueous solution with no significant difference between ME systems (containing 5% and 10% water) as well as o/w emulsion containing 85% water. Conversely, a LC system formulated without cosurfactant displayed a significantly greater retention compared to other formulations. (c) 2005 Elsevier B.V. All rights reserved.

Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain

Aims Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. Methods and results We examined prognosis and cost-effectiveness of exercise echocardiography (n=4884) vs. SPECT (n=4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. Conclusion Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.

Avaliação das inclinações dentárias obtidas no tratamento ortodôntico com bráquetes autoligados utilizando tomografia computadorizada

O objetivo deste trabalho foi analisar a expressão dos torques dentários em pacientes tratados com aparelhos ortodônticos fixos com bráquetes autoligados, utilizando tomografias computadorizadas. Para este estudo, foi selecionada uma amostra clínica de 10 pacientes, seguindo como critérios de inclusão, indivíduos que apresentavam dentição permanente e todos os dentes presentes, com apinhamento superior ou igual a 4 mm, tratados sem extração. Todos os pacientes foram tratados na clínica da pós-graduação em Ortodontia da Universidade Metodista de São Paulo, utilizando-se bráquetes autoligados Damon 2 ORMCO na prescrição padrão. Foram realizadas medições das inclinações dos dentes anteriores, de canino a canino, superiores e inferiores, realizadas por meio de imagens tomográficas obtidas em um tomógrafo computadorizado volumétrico NewTom, em seu modelo DVT-9000 (NIM Verona - Itália), obtidas em dois tempos: antes do início do tratamento ortodôntico (denominado de T1) e depois do tratamento ortodôntico, após a inserção do último fio de nivelamento, de calibre 0,019 x 0,025 de aço inoxidável(denominado de T2). Para auxílio destas mensurações, foi utilizado o software QR-DVT 9000 e após análise dos resultados foram aplicados testes estatíscos (testes "t" pareado e Dalberg) e observou-se que as inclinações dos dentes do segmento anterior aumentaram, principalmente, nos caninos e incisivos laterais superiores, incisivos centrais e laterais inferiores. Os dentes apresentaram valores de inclinação diferentes da prescrição, tanto no início quanto no final do tratamento, denotando a incapacidade do fio 0,019 x 0,025 de aço inoxidável em reproduzir os torques indicados na prescrição padrão utilizada neste presente estudo.(AU)

AVALIAÇÃO TOMOGRÁFICA DA INCLINAÇÃO E DAS TÁBUAS ÓSSEAS VESTIBULAR E LINGUAL DE INCISIVOS NO TRATAMENTO DA CLASSE II DIVISÃO 1 COM O APARELHO FORSUS®

O objetivo deste estudo prospectivo foi avaliar os efeitos do aparelho Forsus® nos incisivos centrais superiores e inferiores. A amostra constituiu-se de 22 tomografias computadorizadas de 11 pacientes (sexo masculino e feminino) idade média de 15,8 anos com má oclusão de Classe II que foram tratados com o aparelho Forsus® na clínica do programa de pós-graduação em Odontologia, área de concentração Ortodontia, da Universidade Metodista de São Paulo. As tomografias foram obtidas em dois momentos T1 (final de nivelamento e antes da instalação do Forsus® e T2 (remoção do Forsus®). Para avaliar a distância do ápice até a tábua óssea, as imagens a serem examinadas foram obtidas com o auxílio do viewer do próprio i-CAT® , o iCATVision® e examinadas com o CorelDRAW X5® já para as medidas cefalométricas IMPA e 1.PP as imagens cefalométricas ortogonais foram obtidas em proporção 1:1 com auxílio do software Dolphin 3D® (Dolphin Imaging and Management Solutions, Chatsworth, EUA) e em seguida examinadas com o software Radiocef Studio 2 (Radio Memory, Belo Horizonte, Brasil). Para a obtenção do erro intra-examinador foi feito o teste t de Student pareado para o erro sistemático e a fórmula de DAHLBERG para estimar a ordem de grandeza dos erros casuais e na análise estatística dos resultados utilizou-se: o teste t para a determinação das diferenças entres as fases de observação e o teste de correlação de Pearson para avaliar a correlação entres as alterações. Observou-se: um aumento significativo (p<0,05) tanto no IMPA quanto no 1.PP, aproximação do ápice dos incisivos inferiores da tábua óssea lingual, aproximação do ápice dos incisivos superiores da tábua óssea vestibular, uma correlação negativa muito forte entre o IMPA e a distância do ápice do incisivo até a tábua óssea lingual e uma correlação negativa moderada entre 1.PP e a distância do ápice do incisivo até a tábua óssea vestibular. Sendo assim o aparelho Forsus® no tratamento da Classe II teve como efeito: vestibularização significativa dos incisivos centrais inferiores, uma verticalização significativa dos incisivos centrais superiores, aproximação do ápice dos incisivos inferiores da cortical óssea lingual e aproximação do ápice dos incisivos superiores da cortical óssea vestibular.

Possibilities and limitations of coded aperture imaging

We have simulated the performance of various apertures used in Coded Aperture Imaging - optically. Coded pictures of extended and continuous-tone planar objects from the Annulus, Twin Annulus, Fresnel Zone Plate and the Uniformly Redundant Array have been decoded using a noncoherent correlation process. We have compared the tomographic capabilities of the Twin Annulus with the Uniformly Redundant Arrays based on quadratic residues and m-sequences. We discuss the ways of reducing the 'd. c.' background of the various apertures used. The non-ideal System-Point-Spread-Function inherent in a noncoherent optical correlation process produces artifacts in the reconstruction. Artifacts are also introduced as a result of unwanted cross-correlation terms from out-of-focus planes. We find that the URN based on m-sequences exhibits good spatial resolution and out-of-focus behaviour when imaging extended objects.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.

Source localization methods

One of the most pressing demands on electrophysiology applied to the diagnosis of epilepsy is the non-invasive localization of the neuronal generators responsible for brain electrical and magnetic fields (the so-called inverse problem). These neuronal generators produce primary currents in the brain, which together with passive currents give rise to the EEG signal. Unfortunately, the signal we measure on the scalp surface doesn't directly indicate the location of the active neuronal assemblies. This is the expression of the ambiguity of the underlying static electromagnetic inverse problem, partly due to the relatively limited number of independent measures available. A given electric potential distribution recorded at the scalp can be explained by the activity of infinite different configurations of intracranial sources. In contrast, the forward problem, which consists of computing the potential field at the scalp from known source locations and strengths with known geometry and conductivity properties of the brain and its layers (CSF/meninges, skin and skull), i.e. the head model, has a unique solution. The head models vary from the computationally simpler spherical models (three or four concentric spheres) to the realistic models based on the segmentation of anatomical images obtained using magnetic resonance imaging (MRI). Realistic models – computationally intensive and difficult to implement – can separate different tissues of the head and account for the convoluted geometry of the brain and the significant inter-individual variability. In real-life applications, if the assumptions of the statistical, anatomical or functional properties of the signal and the volume in which it is generated are meaningful, a true three-dimensional tomographic representation of sources of brain electrical activity is possible in spite of the ‘ill-posed’ nature of the inverse problem (Michel et al., 2004). The techniques used to achieve this are now referred to as electrical source imaging (ESI) or magnetic source imaging (MSI). The first issue to influence reconstruction accuracy is spatial sampling, i.e. the number of EEG electrodes. It has been shown that this relationship is not linear, reaching a plateau at about 128 electrodes, provided spatial distribution is uniform. The second factor is related to the different properties of the source localization strategies used with respect to the hypothesized source configuration.

Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.

Clinical translation of a hand-held optical imager for breast cancer diagnostics: In vitro and in vivo tomography studies

Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ∼2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ∼0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo , although the error in probe’s positional information increased to ∼0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts.

Estudo da estrutura subsuperficial da província Borborema com correlação de ruído sísmico

Ambient seismic noise has traditionally been considered as an unwanted perturbation in seismic data acquisition that "contaminates" the clean recording of earthquakes. Over the last decade, however, it has been demonstrated that consistent information about the subsurface structure can be extracted from cross-correlation of ambient seismic noise. In this context, the rules are reversed: the ambient seismic noise becomes the desired seismic signal, while earthquakes become the unwanted perturbation that needs to be removed. At periods lower than 30 s, the spectrum of ambient seismic noise is dominated by microseism, which originates from distant atmospheric perturbations over the oceans. The microsseism is the most continuous seismic signal and can be classified as primary – when observed in the range 10-20 s – and secondary – when observed in the range 5-10 s. The Green‘s function of the propagating medium between two receivers (seismic stations) can be reconstructed by cross-correlating seismic noise simultaneously recorded at the receivers. The reconstruction of the Green‘s function is generally proportional to the surface-wave portion of the seismic wavefield, as microsseismic energy travels mostly as surface-waves. In this work, 194 Green‘s functions obtained from stacking of one month of daily cross-correlations of ambient seismic noise recorded in the vertical component of several pairs of broadband seismic stations in Northeast Brazil are presented. The daily cross-correlations were stacked using a timefrequency, phase-weighted scheme that enhances weak coherent signals by reducing incoherent noise. The cross-correlations show that, as expected, the emerged signal is dominated by Rayleigh waves, with dispersion velocities being reliably measured for periods ranging between 5 and 20 s. Both permanent stations from a monitoring seismic network and temporary stations from past passive experiments in the region are considered, resulting in a combined network of 33 stations separated by distances between 60 and 1311 km, approximately. The Rayleigh-wave, dispersion velocity measurements are then used to develop tomographic images of group velocity variation for the Borborema Province of Northeast Brazil. The tomographic maps allow to satisfactorily map buried structural features in the region. At short periods (~5 s) the images reflect shallow crustal structure, clearly delineating intra-continental and marginal sedimentary basins, as well as portions of important shear zones traversing the Borborema Province. At longer periods (10 – 20 s) the images are sensitive to deeper structure in the upper crust, and most of the shallower anomalies fade away. Interestingly, some of them do persist. The deep anomalies do not correlate with either the location of Cenozoic volcanism and uplift - which marked the evolution of the Borborema Province in the Cenozoic - or available maps of surface heat-flow, and the origin of the deep anomalies remains enigmatic.

Classificação de nódulos pulmonares em imagens tomográficas utilizando redes neurais artificiais em cascata

Lung cancer is the most common of malignant tumors, with 1.59 million new cases worldwide in 2012. Early detection is the main factor to determine the survival of patients affected by this disease. Furthermore, the correct classification is important to define the most appropriate therapeutic approach as well as suggest the prognosis and the clinical disease evolution. Among the exams used to detect lung cancer, computed tomography have been the most indicated. However, CT images are naturally complex and even experts medical are subject to fault detection or classification. In order to assist the detection of malignant tumors, computer-aided diagnosis systems have been developed to aid reduce the amount of false positives biopsies. In this work it was developed an automatic classification system of pulmonary nodules on CT images by using Artificial Neural Networks. Morphological, texture and intensity attributes were extracted from lung nodules cut tomographic images using elliptical regions of interest that they were subsequently segmented by Otsu method. These features were selected through statistical tests that compare populations (T test of Student and U test of Mann-Whitney); from which it originated a ranking. The features after selected, were inserted in Artificial Neural Networks (backpropagation) to compose two types of classification; one to classify nodules in malignant and benign (network 1); and another to classify two types of malignancies (network 2); featuring a cascade classifier. The best networks were associated and its performance was measured by the area under the ROC curve, where the network 1 and network 2 achieved performance equal to 0.901 and 0.892 respectively.

Micromachined silicon lenses for terahertz applications

Silicon microlenses are a very important tool for coupling terahertz (THz) radiation into antennas and detectors in integrated circuits. They can be used in a large array structures at this frequency range reducing considerably the crosstalk between the pixels. Drops of photoresist have been deposited and their shape transferred into the silicon by means of a Reactive Ion Etching (RIE) process. Large silicon lenses with a few mm diameter (between 1.5 and 4.5 mm) and hundreds of μm height (between 50 and 350 μm) have been fabricated. The surface of such lenses has been characterized using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM), resulting in a surface roughness of about ∼3 μm, good enough for any THz application. The beam profile at the focal plane of such lenses has been measured at a wavelength of 10.6 μm using a tomographic knife-edge technique and a CO2 laser.