Non-invasive detection of acute cell-mediated graft rejection in paediatric heart transplant recipients: the role of cardiovascular magnetic resonance

Background and Aim: Acute cardiac rejection is currently diagnosed by endomyocardial biopsy (EMB), but multiparametric cardiac magnetic resonance (CMR) may be a non-invasive alternative by its capacity for myocardial structure and function characterization. Our primary aim was to determine the utility of multiparametric CMR in identifying acute graft rejection in paediatric heart transplant recipients. The second aim was to compare textural features of parametric maps in cases of rejection versus those without rejection. Methods: Fifteen patients were prospectively enrolled for contrast-enhanced CMR followed by EMB and right heart catheterization. Images were acquired on a 1,5 Tesla scanner including T1 mapping (modified Look-Locker inversion recovery sequence – MOLLI) and T2 mapping (modified GraSE sequence). The extracellular volume (ECV) was calculated using pre- and post-gadolinium T1 times of blood and myocardium and the patient’s hematocrit. Markers of graft dysfunction including hemodynamic measurements from echocardiography, catheterization and CMR were collated. Patients were divided into two groups based on degree of rejection at EMB: no rejection with no change in treatment (Group A) and acute rejection requiring new therapy (Group B). Statistical analysis included student’t t test and Pearson correlation. Results: Acute rejection was diagnosed in five patients. Mean T1 values were significantly associated with acute rejection. A monotonic, increasing trend was noted in both mean and peak T1 values, with increasing degree of rejection. ECV was significantly higher in Group B. There was no difference in T2 signal between two groups. Conclusion: Multiparametric CMR serves as a noninvasive screening tool during surveillance encounters and may be used to identify those patients that may be at higher risk of rejection and therefore require further evaluation. Future and multicenter studies are necessary to confirm these results and explore whether multiparametric CMR can decrease the number of surveillance EMBs in paediatric heart transplant recipients.

Validação de um radioimunoensaio para a quantificação de metabólitos fecais de testosterona em hamster Sírio (Mesocricetus auratus)

Modelo para o estudo de diversas doenças humanas, o hamster tem sido objeto de numerosos estudos comportamentais e envolvendo estresse e/ou comportamento agonístico que supõem, muitas vezes, o monitoramento das flutuações hormonais nos indivíduos envolvidos. O objetivo do presente trabalho foi confirmar a adequação de um conjunto comercial para dosagem de testosterona em sangue humano para a quantificação de metabólitos fecais de testosterona (MFT) em hamsters Sírios machos e fêmeas. Dez machos foram submetidos a um desafio com um agonista de GnRH para estimular a atividade testicular, elevando os níveis circulantes de testosterona. Cinco fêmeas receberam uma injeção de testosterona enquanto cinco outras receberam uma injeção de solução salina. Amostras de fezes coletadas antes e depois dos procedimentos, assim como amostras fecais de 20 fêmeas gestantes coletadas ao longo da gestação foram analisadas com um conjunto comercial para radioimunoensaio. Um pico de MFT 12h após a injeção seguido de uma queda abaixo do nível basal comprovou que, nos machos, as alterações nos níveis de MFT refletem as alterações da concentração de testosterona no sangue. Nestes observou-se um ciclo circadiano das concentrações de MFT com acrofase no início do período claro correspondendo ao ciclo descrito para as concentrações sanguíneas na literatura. Nas fêmeas a administração de testosterona exógena provocou uma elevação importante dos níveis de MFT, mas as concentrações medidas ao longo da gestação não refletiram o padrão dos níveis sanguíneos do hormônio endógeno. O conjunto para radioimunoensaio para testosterona em sangue humano mostrou-se adequado para o monitoramento da função testicular no hamster macho, mas um ensaio mais específico seria necessário para as fêmeas.

Zerebrale Probleme in der pädiatrischen Intensivmedizin [Cerebral problems in pediatric intensive care]

This paper presents a review of different methods enabling the monitoring of cerebral function in neonatal and paediatric intensive care. EEG, evoked potentials, conventional radiological studies, computerized tomography, ultrasound, intracranial pressure measurements, nuclear magnetic resonance, Doppler ultrasound, radioisotope studies, angiography, infra-red spectral analysis and last, but not least, clinical examination produce information regarding the neurological state of the patient which must be critically analysed in order to ensure optimal management of the case. Unfortunately, and in spite of impressive progress in non-invasive monitoring of the cerebral function, we are still forced to make important medical and ethical decisions without precise information about the neurological state of our patients.

How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Comparison of two methods for glucocorticoid evaluation in maned wolves

Analysis of faecal glucocorticoid metabolites provides a powerful noninvasive tool for monitoring adrenocortical activity in wild animals. However, differences regarding the metabolism and excretion of these substances make a validation for each species and sex investigated obligatory. Although maned wolves (Chrysocyon brachyurus) are the biggest canids in South America, their behaviour and physiology are poorly known and they are at risk in the wild. Two methods for measuring glucocorticoid metabolites in maned wolves were validated: a radio- and an enzyme immunoassay. An ACTH challenge was used to demonstrate that changes in adrenal function are reflected in faecal glucocorticoid metabolites. Our results suggest that both methods enable a reliable assessment of stress hormones in maned wolves avoiding short-term rises in glucocorticoid concentrations due to handling and restraint. These methods can be used as a valuable tool in studies of stress and conservation in this wild species.

Métodos não-invasivos para análises hormonais aplicadas aos estudos de ecologia e etologia

O monitoramento endócrino pela mensuração de metabólitos urinários e fecais de hormônios esteróides tem se mostrado uma alternativa viável na investigação da fisiologia reprodutiva e do estresse em uma grande variedade de aves e mamíferos, domésticos e selvagens. Esta abordagem tem contribuído para uma maior integração da endocrinologia com estudos comportamentais e ecológicos, gerando informações mais detalhadas em diversas áreas tais como bem-estar animal, comportamento social, reprodução, biologia da conservação, biomedicina, entre outros. Todavia, o emprego desta metodologia no Brasil tem sido limitado principalmente à pesquisa de parâmetros reprodutivos e de estresse em espécies selvagens, não havendo até o momento trabalhos publicados utilizando a quantificação urinária ou fecal de glucocorticóides ou esteróides sexuais em animais domésticos. Desta forma, esta palestra tem como objetivo ilustrar alguns exemplos de estudos conduzidos no país envolvendo técnicas de monitoramento endócrino não-invasivo, assim como expor possíveis áreas de aplicação desta ferramenta em pesquisas com espécies domesticas.

Disfunção arterial como possível mecanismo de agressão cardíaca em pacientes com diabetes mellitus tipo II. Estudo Doppler-ecocardiográfico

OBJETIVO: Avaliar a estrutura e função do ventrículo esquerdo (VE) e a rigidez arterial em portadores de diabetes mellitus tipo II. MÉTODOS: Foram estudados 13 doentes diabéticos de ambos os sexos (55±8 anos) sem outras doenças. A estrutura e função do VE foram avaliadas por meio de ecodopplercardiografia associada à monitorização não invasiva da pressão arterial (PA). Os resultados foram comparados aos obtidos em grupo de indivíduos normais de mesma idade (n=12). RESULTADOS: Não houve diferenças entre os grupos quanto a PA diastólica, dimensões das câmaras esquerdas e índices de função sistólica e diastólica. Os pacientes diabéticos apresentaram índice de massa do VE (101±10 vs 80±14g/m²; p<0,001) e índice de rigidez arterial sistêmica (0,86±0,26 vs 0,69±0,19mmHg/mL; p<0,05) significantemente maiores que os controles. CONCLUSÃO: O diabetes mellitus está associado a aumento da rigidez arterial sistêmica e esse fator poderia contribuir para seus efeitos adversos sobre o VE.

Localização de descargas parciais em transformadores de potência por meio de sensores piezelétricos de baixo custo e sistemas inteligentes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Localização de descargas parciais em transformadores de potência por meio de sensores piezelétricos de baixo custo e sistemas inteligentes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Abdominal magnetic resonance imaging in small rodents using a clinical 1.5 T MR scanner

Because of superior soft-tissue contrast compared to other imaging techniques, non-invasive abdominal magnetic resonance imaging (MRI) is ideal for monitoring organ regeneration, tissue repair, cancer stage, and treatment effects in a wide variety of experimental animal models. Currently, sophisticated MR protocols, including technically demanding procedures for motion artefact compensation, achieve an MRI resolution limit of < 100 microm under ideal conditions. However, such a high spatial resolution is not required for most experimental rodent studies. This article describes both a detailed imaging protocol for MR data acquisition in a ubiquitously and commercially available 1.5 T MR unit and 3-dimensional volumetry of organs, tissue components, or tumors. Future developments in MR technology will allow in vivo investigation of physiological and pathological processes at the cellular and even the molecular levels. Experimental MRI is crucial for non-invasive monitoring of a broad range of biological processes and will further our general understanding of physiology and disease.

Aportación de la monitorización mediante redes de sensores y técnicas no invasivas para la conservación preventiva del Patrimonio

La presente tesis doctoral presenta una serie de estudios en el campo del patrimonio basados en metodologías de monitorización mediante redes de sensores y técnicas no invasivas con el objetivo de realizar nuevas aportaciones a la conservación preventiva mediante el seguimiento de los daños de deterioro o la prevención de los mismos. Las metodologías de monitorización mediante el despliegue de redes tridimensionales basadas en data loggers abordan estudios microclimáticos, de confort y energéticos a corto plazo, donde se establecen conclusiones relativas a la eficiencia energética de tres sistemas de calefacción muy utilizados en iglesias de la región centro de la Península Ibérica, abordando aspectos de afección de los mismos en el confort de los ocupantes o en el deterioro de los elementos patrimoniales o constructivos. Se desplegaron además distintas plataformas de redes de sensores inalámbricas procediendo a analizar en esta tesis cuál es la que presenta mejores resultados en el ámbito del patrimonio con el objetivo de una monitorización a largo plazo y considerando aspectos de comunicaciones, consumo y configuración de las redes. Una vez conocida la plataforma que presenta mejores resultados comparativos se muestra una metodología de estudio de la calidad de las comunicaciones en múltiples escenarios de patrimonio cultural y natural con la misma, que servirá para establecer una serie de aspectos a considerar en el despliegue de redes de sensores inalámbricas en futuros escenarios a monitorizar. Al igual que ocurre con las redes de sensores basadas en data loggers, las tareas de monitorización desarrolladas en esta tesis mediante el despliegue de las distintas plataformas inalámbricas ha permitido la detección de numerosos fenómenos de deterioro que son descritos a lo largo de la investigación y cuyo seguimiento supone una aportación a la prevención de daños en los distintos escenarios. Asimismo en el desarrollo de la tesis se realiza una aportación para la conservación preventiva mediante la monitorización con distintas técnicas no invasivas como la termografía infrarroja, las medidas de humedad superficial mediante protimeter, las técnicas de prospección de resistividad eléctrica de alta resolución o la prospección georradar. De este modo se desarrollan distintas aportaciones y conclusiones acerca de las ventajas y/o limitaciones de uso de las mismas analizando la idoneidad de aplicar cada una de ellas en distintas fases de análisis o con distintas capacidades de detección o caracterización de los daños. El estudio de imbricación de dichas técnicas ha sido desarrollado en un escenario real que presenta graves daños por humedad, habiendo sido posible la caracterización del origen de los mismos. ABSTRACT This doctoral dissertation discusses field research conducted to monitor heritage assets with sensor networks and other non-invasive techniques. The aim pursued was to contribute to conservation by tracking or preventing decay-induced damage. Monitoring methodologies based on three-dimensional data logger networks were used in short-term micro-climatic, comfort and energy studies to draw conclusions about the energy efficiency of three heating systems widely used in central Iberian churches. The impact of these systems on occupant comfort and decay of heritage or built elements was also explored. Different wireless sensor platforms were deployed and analysed to determine which delivered the best results in the context of long-term heritage monitoring from the standpoints of communications, energy demand and network architecture. A methodology was subsequently designed to study communication quality in a number of cultural and natural heritage scenarios and help establish the considerations to be borne in mind when deploying wireless sensor networks for heritage monitoring in future. As in data logger-based sensor networks, the monitoring conducted in this research with wireless platforms identified many instances of decay, described hereunder. Tracking those situations will help prevent damage in the respective scenarios. The research also contributes to preventive conservation based on non-invasive monitoring using techniques such as infrared thermography, protimeter-based surface damp measurements, high resolution electrical resistivity surveys and georadar analysis. The conclusions drawn address the advantages and drawbacks of each technique and its suitability for the various phases of analysis and capacity to detect or characterise damage. This dissertation also describes the intermeshed usage of these techniques that led to the identification of the origin of severe damp-induced damage in a real scenario.

Use of regression equation of peripheral pulse timing characteristics to predict hypertension in children

Studies have shown that an increase in arterial stiffening can indicate the presence of cardiovascular diseases like hypertension. Current gold standard in clinical practice is by measuring the blood pressure of patients using a mercury sphygmomanometer. However, the nature of this technique is not suitable for prolonged monitoring. It has been established that pulse wave velocity is a direct measure of arterial stiffening. However, its usefulness is hampered by the absence of techniques to estimate it non-invasively. Pulse transit time (PTT) is a simple and non-intrusive method derived from pulse wave velocity. It has shown its capability in childhood respiratory sleep studies. Recently, regression equations that can predict PTT values for healthy Caucasian children were formulated. However, its usefulness to identify hypertensive children based on mean PTT values has not been investigated. This was a continual study where 3 more Caucasian male children with known clinical hypertension were recruited. Results indicated that the PTT predictive equations are able to identify hypertensive children from their normal counterparts in a significant manner (p < 0.05). Hence, PTT can be a useful diagnostic tool in identifying hypertension in children and shows potential to be a non-invasive continual monitor for arterial stiffening.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.

Efficient and low-computational predictive models for spectral sensors

Spectral sensors are a wide class of devices that are extremely useful for detecting essential information of the environment and materials with high degree of selectivity. Recently, they have achieved high degrees of integration and low implementation cost to be suited for fast, small, and non-invasive monitoring systems. However, the useful information is hidden in spectra and it is difficult to decode. So, mathematical algorithms are needed to infer the value of the variables of interest from the acquired data. Between the different families of predictive modeling, Principal Component Analysis and the techniques stemmed from it can provide very good performances, as well as small computational and memory requirements. For these reasons, they allow the implementation of the prediction even in embedded and autonomous devices. In this thesis, I will present 4 practical applications of these algorithms to the prediction of different variables: moisture of soil, moisture of concrete, freshness of anchovies/sardines, and concentration of gasses. In all of these cases, the workflow will be the same. Initially, an acquisition campaign was performed to acquire both spectra and the variables of interest from samples. Then these data are used as input for the creation of the prediction models, to solve both classification and regression problems. From these models, an array of calibration coefficients is derived and used for the implementation of the prediction in an embedded system. The presented results will show that this workflow was successfully applied to very different scientific fields, obtaining autonomous and non-invasive devices able to predict the value of physical parameters of choice from new spectral acquisitions.