Single breath-hold 3D measurement of left atrial volume using compressed sensing cardiovascular magnetic resonance and a non-model-based reconstruction approach.

BACKGROUND: Left atrial (LA) dilatation is associated with a large variety of cardiac diseases. Current cardiovascular magnetic resonance (CMR) strategies to measure LA volumes are based on multi-breath-hold multi-slice acquisitions, which are time-consuming and susceptible to misregistration. AIM: To develop a time-efficient single breath-hold 3D CMR acquisition and reconstruction method to precisely measure LA volumes and function. METHODS: A highly accelerated compressed-sensing multi-slice cine sequence (CS-cineCMR) was combined with a non-model-based 3D reconstruction method to measure LA volumes with high temporal and spatial resolution during a single breath-hold. This approach was validated in LA phantoms of different shapes and applied in 3 patients. In addition, the influence of slice orientations on accuracy was evaluated in the LA phantoms for the new approach in comparison with a conventional model-based biplane area-length reconstruction. As a reference in patients, a self-navigated high-resolution whole-heart 3D dataset (3D-HR-CMR) was acquired during mid-diastole to yield accurate LA volumes. RESULTS: Phantom studies. LA volumes were accurately measured by CS-cineCMR with a mean difference of -4.73 ± 1.75 ml (-8.67 ± 3.54%, r2 = 0.94). For the new method the calculated volumes were not significantly different when different orientations of the CS-cineCMR slices were applied to cover the LA phantoms. Long-axis "aligned" vs "not aligned" with the phantom long-axis yielded similar differences vs the reference volume (-4.87 ± 1.73 ml vs. -4.45 ± 1.97 ml, p = 0.67) and short-axis "perpendicular" vs. "not-perpendicular" with the LA long-axis (-4.72 ± 1.66 ml vs. -4.75 ± 2.13 ml; p = 0.98). The conventional bi-plane area-length method was susceptible for slice orientations (p = 0.0085 for the interaction of "slice orientation" and "reconstruction technique", 2-way ANOVA for repeated measures). To use the 3D-HR-CMR as the reference for LA volumes in patients, it was validated in the LA phantoms (mean difference: -1.37 ± 1.35 ml, -2.38 ± 2.44%, r2 = 0.97). Patient study: The CS-cineCMR LA volumes of the mid-diastolic frame matched closely with the reference LA volume (measured by 3D-HR-CMR) with a difference of -2.66 ± 6.5 ml (3.0% underestimation; true LA volumes: 63 ml, 62 ml, and 395 ml). Finally, a high intra- and inter-observer agreement for maximal and minimal LA volume measurement is also shown. CONCLUSIONS: The proposed method combines a highly accelerated single-breathhold compressed-sensing multi-slice CMR technique with a non-model-based 3D reconstruction to accurately and reproducibly measure LA volumes and function.

Iterative reconstruction in CT : using mathematical model observers to determine low dose images' trustworthiness

La tomodensitométrie (TDM) est une technique d'imagerie pour laquelle l'intérêt n'a cessé de croitre depuis son apparition au début des années 70. De nos jours, l'utilisation de cette technique est devenue incontournable, grâce entre autres à sa capacité à produire des images diagnostiques de haute qualité. Toutefois, et en dépit d'un bénéfice indiscutable sur la prise en charge des patients, l'augmentation importante du nombre d'examens TDM pratiqués soulève des questions sur l'effet potentiellement dangereux des rayonnements ionisants sur la population. Parmi ces effets néfastes, l'induction de cancers liés à l'exposition aux rayonnements ionisants reste l'un des risques majeurs. Afin que le rapport bénéfice-risques reste favorable au patient il est donc nécessaire de s'assurer que la dose délivrée permette de formuler le bon diagnostic tout en évitant d'avoir recours à des images dont la qualité est inutilement élevée. Ce processus d'optimisation, qui est une préoccupation importante pour les patients adultes, doit même devenir une priorité lorsque l'on examine des enfants ou des adolescents, en particulier lors d'études de suivi requérant plusieurs examens tout au long de leur vie. Enfants et jeunes adultes sont en effet beaucoup plus sensibles aux radiations du fait de leur métabolisme plus rapide que celui des adultes. De plus, les probabilités des évènements auxquels ils s'exposent sont également plus grandes du fait de leur plus longue espérance de vie. L'introduction des algorithmes de reconstruction itératifs, conçus pour réduire l'exposition des patients, est certainement l'une des plus grandes avancées en TDM, mais elle s'accompagne de certaines difficultés en ce qui concerne l'évaluation de la qualité des images produites. Le but de ce travail est de mettre en place une stratégie pour investiguer le potentiel des algorithmes itératifs vis-à-vis de la réduction de dose sans pour autant compromettre la qualité du diagnostic. La difficulté de cette tâche réside principalement dans le fait de disposer d'une méthode visant à évaluer la qualité d'image de façon pertinente d'un point de vue clinique. La première étape a consisté à caractériser la qualité d'image lors d'examen musculo-squelettique. Ce travail a été réalisé en étroite collaboration avec des radiologues pour s'assurer un choix pertinent de critères de qualité d'image. Une attention particulière a été portée au bruit et à la résolution des images reconstruites à l'aide d'algorithmes itératifs. L'analyse de ces paramètres a permis aux radiologues d'adapter leurs protocoles grâce à une possible estimation de la perte de qualité d'image liée à la réduction de dose. Notre travail nous a également permis d'investiguer la diminution de la détectabilité à bas contraste associée à une diminution de la dose ; difficulté majeure lorsque l'on pratique un examen dans la région abdominale. Sachant que des alternatives à la façon standard de caractériser la qualité d'image (métriques de l'espace Fourier) devaient être utilisées, nous nous sommes appuyés sur l'utilisation de modèles d'observateurs mathématiques. Nos paramètres expérimentaux ont ensuite permis de déterminer le type de modèle à utiliser. Les modèles idéaux ont été utilisés pour caractériser la qualité d'image lorsque des paramètres purement physiques concernant la détectabilité du signal devaient être estimés alors que les modèles anthropomorphes ont été utilisés dans des contextes cliniques où les résultats devaient être comparés à ceux d'observateurs humain, tirant profit des propriétés de ce type de modèles. Cette étude a confirmé que l'utilisation de modèles d'observateurs permettait d'évaluer la qualité d'image en utilisant une approche basée sur la tâche à effectuer, permettant ainsi d'établir un lien entre les physiciens médicaux et les radiologues. Nous avons également montré que les reconstructions itératives ont le potentiel de réduire la dose sans altérer la qualité du diagnostic. Parmi les différentes reconstructions itératives, celles de type « model-based » sont celles qui offrent le plus grand potentiel d'optimisation, puisque les images produites grâce à cette modalité conduisent à un diagnostic exact même lors d'acquisitions à très basse dose. Ce travail a également permis de clarifier le rôle du physicien médical en TDM: Les métriques standards restent utiles pour évaluer la conformité d'un appareil aux requis légaux, mais l'utilisation de modèles d'observateurs est inévitable pour optimiser les protocoles d'imagerie. -- Computed tomography (CT) is an imaging technique in which interest has been quickly growing since it began to be used in the 1970s. Today, it has become an extensively used modality because of its ability to produce accurate diagnostic images. However, even if a direct benefit to patient healthcare is attributed to CT, the dramatic increase in the number of CT examinations performed has raised concerns about the potential negative effects of ionising radiation on the population. Among those negative effects, one of the major risks remaining is the development of cancers associated with exposure to diagnostic X-ray procedures. In order to ensure that the benefits-risk ratio still remains in favour of the patient, it is necessary to make sure that the delivered dose leads to the proper diagnosis without producing unnecessarily high-quality images. This optimisation scheme is already an important concern for adult patients, but it must become an even greater priority when examinations are performed on children or young adults, in particular with follow-up studies which require several CT procedures over the patient's life. Indeed, children and young adults are more sensitive to radiation due to their faster metabolism. In addition, harmful consequences have a higher probability to occur because of a younger patient's longer life expectancy. The recent introduction of iterative reconstruction algorithms, which were designed to substantially reduce dose, is certainly a major achievement in CT evolution, but it has also created difficulties in the quality assessment of the images produced using those algorithms. The goal of the present work was to propose a strategy to investigate the potential of iterative reconstructions to reduce dose without compromising the ability to answer the diagnostic questions. The major difficulty entails disposing a clinically relevant way to estimate image quality. To ensure the choice of pertinent image quality criteria this work was continuously performed in close collaboration with radiologists. The work began by tackling the way to characterise image quality when dealing with musculo-skeletal examinations. We focused, in particular, on image noise and spatial resolution behaviours when iterative image reconstruction was used. The analyses of the physical parameters allowed radiologists to adapt their image acquisition and reconstruction protocols while knowing what loss of image quality to expect. This work also dealt with the loss of low-contrast detectability associated with dose reduction, something which is a major concern when dealing with patient dose reduction in abdominal investigations. Knowing that alternative ways had to be used to assess image quality rather than classical Fourier-space metrics, we focused on the use of mathematical model observers. Our experimental parameters determined the type of model to use. Ideal model observers were applied to characterise image quality when purely objective results about the signal detectability were researched, whereas anthropomorphic model observers were used in a more clinical context, when the results had to be compared with the eye of a radiologist thus taking advantage of their incorporation of human visual system elements. This work confirmed that the use of model observers makes it possible to assess image quality using a task-based approach, which, in turn, establishes a bridge between medical physicists and radiologists. It also demonstrated that statistical iterative reconstructions have the potential to reduce the delivered dose without impairing the quality of the diagnosis. Among the different types of iterative reconstructions, model-based ones offer the greatest potential, since images produced using this modality can still lead to an accurate diagnosis even when acquired at very low dose. This work has clarified the role of medical physicists when dealing with CT imaging. The use of the standard metrics used in the field of CT imaging remains quite important when dealing with the assessment of unit compliance to legal requirements, but the use of a model observer is the way to go when dealing with the optimisation of the imaging protocols.

Transgenic mice overexpressing neuropeptide Y: An experimental model of metabolic and cardiovascular diseases

Neuropeptide Y (NPY) is an abundant neurotransmitter in the brain and sympathetic nervous system (SNS). Hypothalamic NPY is known to be a key player in food intake and energy expenditure. NPY’s role in cardiovascular regulation has also been shown. In humans, a Leucine 7 to Proline 7 single nucleotide polymorphism (p.L7P) in the signal peptide of the NPY gene has been associated with traits of metabolic syndrome. The p.L7P subjects also show increased stress-related release of NPY, which suggests that more NPY is produced and released from SNS. The main objective of this study was to create a novel mouse model with noradrenergic cell-targeted overexpression of NPY, and to characterize the metabolic and vascular phenotype of this model. The mouse model was named OE-NPY^DBH mouse. Overexpression of NPY in SNS and brain noradrenergic neurons led to increased adiposity without significant weight gain or increased food intake. The mice showed lipid accumulation in the liver at young age, which together with adiposity led to impaired glucose tolerance and hyperinsulinemia with age. The mice displayed stress-related increased mean arterial blood pressure, increased plasma levels of catecholamines and enhanced SNS activity measured by GDP binding activity to brown adipose tissue mitochondria. Sexual dimorphism in NPY secretion pattern in response to stress was also seen. In an experimental model of vascular injury, the OE-NPY^DBH mice developed more pronounced neointima formation compared with wildtype controls. These results together with the clinical data indicate that NPY in noradrenergic cells plays an important role in the pathogenesis of metabolic syndrome and related diseases. Furthermore, new insights on the role of the extrahypothalamic NPY in the process have been obtained. The OE-NPY^DBH model provides an important tool for further stress and metabolic syndrome-related studies.

Mathematical model to estimate of the deterioration of wooden poles in contact with soil used in rural areas

In São Paulo State, mainly in rural areas, the utilization of wooden poles is observed for different purposes. In this context, wood in contact with the ground presents faster deterioration, which is generally associated to environmental factors and, especially to the presence of fungi and insects. With the use of mathematical models, the useful life of wooden structures can be predicted by obtaining "climatic indexes" to indicate, comparatively among the areas studied, which have more or less tendency to fungi and insects attacks. In this work, by using climatological data of several cities at São Paulo State, a simplified mathematical model was obtained to measure the aggressiveness of the wood in contact with the soil.

Evaluation of a new mathematical model to describe Clostridium perfringens growth during the cooling of cooked ground beef

A mathematical model previously developed to study microbial growth in food products under an isothermal environment was adapted to a time-varying temperature regime. The resulting model was applied to study the growth of Clostridium perfringens in meat products. This micro-organism is of particular relevance to public health and economy due to the loss of productivity caused by it. Results showed a similar performance of the model used compared to the Baranyi model under an isothermal situation and a slightly better performance under a non-isothermal temperature profile.

Cardiovascular and sensory abnormalities in a rat model of insulin resistance : beneficial effect of an antioxidant and an angiotensin-1 converting enzyme inhibitor

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

An integrated mathematical model to evaluate nutrient partition in dairy cattle between the animal and its environment

In the past decade, a number of mechanistic, dynamic simulation models of several components of the dairy production system have become available. However their use has been limited due to the detailed technical knowledge and special software required to run them, and the lack of compatibility between models in predicting various metabolic processes in the animal. The first objective of the current study was to integrate the dynamic models of [Brit. J. Nutr. 72 (1994) 679] on rumen function, [J. Anim. Sci. 79 (2001) 1584] on methane production, [J. Anim. Sci. 80 (2002) 2481 on N partition, and a new model of P partition. The second objective was to construct a decision support system to analyse nutrient partition between animal and environment. The integrated model combines key environmental pollutants such as N, P and methane within a nutrient-based feed evaluation system. The model was run under different scenarios and the sensitivity of various parameters analysed. A comparison of predictions from the integrated model with the original simulation models showed an improvement in N excretion since the integrated model uses the dynamic model of [Brit. J. Nutr. 72 (1994) 6791 to predict microbial N, which was not represented in detail in the original model. The integrated model can be used to investigate the degree to which production and environmental objectives are antagonistic, and it may help to explain and understand the complex mechanisms involved at the ruminal and metabolic levels. A part of the integrated model outputs were the forms of N and P in excreta and methane, which can be used as indices of environmental pollution. (C) 2004 Elsevier B.V All rights reserved.

A mathematical model of the in vitro keratinocyte response to chromium and nickel exposure

A mathematical model describing the main mechanistic processes involved in keratinocyte response to chromium and nickel has been developed and compared to experimental in vitro data. Accounting for the interactions between the metal ions and the keratinocytes, the law of mass action was used to generate ordinary differential equations which predict the time evolution and ion concentration dependency of keratinocyte viability, the amount of metal associated with the keratinocytes and the release of cytokines by the keratinocytes. Good agreement between model predictions and existing experimental data of these endpoints was observed, supporting the use of this model to explore physiochemical parameters that influence the toxicological response of keratinocytes to these two metals.

Understanding post-operative temperature drop in cardiac surgery: a mathematical model

A mathematical model is presented to understand heat transfer processes during the cooling and re-warming of patients during cardiac surgery. Our compartmental model is able to account for many of the qualitative features observed in the cooling of various regions of the body including the central core containing the majority of organs, the rectal region containing the intestines and the outer peripheral region of skin and muscle. In particular, we focus on the issue of afterdrop: a drop in core temperature following patient re-warming, which can lead to serious post-operative complications. Model results for a typical cooling and re-warming procedure during surgery are in qualitative agreement with experimental data in producing the afterdrop effect and the observed dynamical variation in temperature between the core, rectal and peripheral regions. The influence of heat transfer processes and the volume of each compartmental region on the afterdrop effect is discussed. We find that excess fat on the peripheral and rectal regions leads to an increase in the afterdrop effect. Our model predicts that, by allowing constant re-warming after the core temperature has been raised, the afterdrop effect will be reduced.

Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell

Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area.

Overview of mathematical approaches used to model bacterial chemotaxis II: bacterial populations

We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The application of continuum mathematical models, in particular generalized Keller-Segel models, is discussed along with attempts to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial populations. Various aspects of each model are discussed and areas for possible future research are postulated.

Mathematical model for low density lipoprotein (LDL) endocytosis by hepatocytes

Individuals with elevated levels of plasma low density lipoprotein (LDL) cholesterol (LDL-C) are considered to be at risk of developing coronary heart disease. LDL particles are removed from the blood by a process known as receptor-mediated endocytosis, which occurs mainly in the liver. A series of classical experiments delineated the major steps in the endocytotic process; apolipoprotein B-100 present on LDL particles binds to a specific receptor (LDL receptor, LDL-R) in specialized areas of the cell surface called clathrin-coated pits. The pit comprising the LDL-LDL-R complex is internalized forming a cytoplasmic endosome. Fusion of the endosome with a lysosome leads to degradation of the LDL into its constituent parts (that is, cholesterol, fatty acids, and amino acids), which are released for reuse by the cell, or are excreted. In this paper, we formulate a mathematical model of LDL endocytosis, consisting of a system of ordinary differential equations. We validate our model against existing in vitro experimental data, and we use it to explore differences in system behavior when a single bolus of extracellular LDL is supplied to cells, compared to when a continuous supply of LDL particles is available. Whereas the former situation is common to in vitro experimental systems, the latter better reflects the in vivo situation. We use asymptotic analysis and numerical simulations to study the longtime behavior of model solutions. The implications of model-derived insights for experimental design are discussed.

Modelling oil absorption during post-frying cooling - II: solution of the mathematical model, model testing and simulations

The mathematical models that describe the immersion-frying period and the post-frying cooling period of an infinite slab or an infinite cylinder were solved and tested. Results were successfully compared with those found in the literature or obtained experimentally, and were discussed in terms of the hypotheses and simplifications made. The models were used as the basis of a sensitivity analysis. Simulations showed that a decrease in slab thickness and core heat capacity resulted in faster crust development. On the other hand, an increase in oil temperature and boiling heat transfer coefficient between the oil and the surface of the food accelerated crust formation. The model for oil absorption during cooling was analysed using the tested post-frying cooling equation to determine the moment in which a positive pressure driving force, allowing oil suction within the pore, originated. It was found that as crust layer thickness, pore radius and ambient temperature decreased so did the time needed to start the absorption. On the other hand, as the effective convective heat transfer coefficient between the air and the surface of the slab increased the required cooling time decreased. In addition, it was found that the time needed to allow oil absorption during cooling was extremely sensitive to pore radius, indicating the importance of an accurate pore size determination in future studies.

A mathematical model, implementation and study of a swarm system

The work reported in this paper is motivated towards the development of a mathematical model for swarm systems based on macroscopic primitives. A pattern formation and transformation model is proposed. The pattern transformation model comprises two general methods for pattern transformation, namely a macroscopic transformation method and a mathematical transformation method. The problem of transformation is formally expressed and four special cases of transformation are considered. Simulations to confirm the feasibility of the proposed models and transformation methods are presented. Comparison between the two transformation methods is also reported.