An unfitted radial basis function generated finite difference method applied to thoracic diaphragm simulations

The thoracic diaphragm is the muscle that drives the respiratory cycle of a human being. Using a system of partial differential equations (PDEs) that models linear elasticity we compute displacements and stresses in a two-dimensional cross section of the diaphragm in its contracted state. The boundary data consists of a mix of displacement and traction conditions. If these are imposed as they are, and the conditions are not compatible, this leads to reduced smoothness of the solution. Therefore, the boundary data is first smoothed using the least-squares radial basis function generated finite difference (RBF-FD) framework. Then the boundary conditions are reformulated as a Robin boundary condition with smooth coefficients. The same framework is also used to approximate the boundary curve of the diaphragm cross section based on data obtained from a slice of a computed tomography (CT) scan. To solve the PDE we employ the unfitted least-squares RBF-FD method. This makes it easier to handle the geometry of the diaphragm, which is thin and non-convex. We show numerically that our solution converges with high-order towards a finite element solution evaluated on a fine grid. Through this simplified numerical model we also gain an insight into the challenges associated with the diaphragm geometry and the boundary conditions before approaching a more complex three-dimensional model

Single fibre cytoarchitecture in ventilator-induced diaphragm dysfunction (VIDD) assessed by quantitative morphometry second harmonic generation imaging: Positive effects of BGP-15 chaperone co-inducer and VBP-15 dissociative corticosteroid treatment

Ventilator-induced diaphragm dysfunction (VIDD) is a common sequela of intensive care unit (ICU) treatment requiring mechanical ventilation (MV) and neuromuscular blockade (NMBA). It is characterised by diaphragm weakness, prolonged respirator weaning and adverse outcomes. Dissociative glucocorticoids (e.g., vamorolone, VBP-15) and chaperone co-inducers (e.g., BGP-15) previously showed positive effects in an ICU-rat model. In limb muscle critical illness myopathy, preferential myosin loss prevails, while myofibrillar protein post-translational modifications are more dominant in VIDD. It is not known whether the marked decline in specific force (force normalised to cross-sectional area) is a pure consequence of altered contractility signaling or whether diaphragm weakness also has a structural correlate through sterical remodeling of myofibrillar cytoarchitecture, how quickly it develops, and to which extent VBP-15 or BGP-15 may specifically recover myofibrillar geometry. To address these questions, we performed label-free multiphoton Second Harmonic Generation (SHG) imaging followed by quantitative morphometry in single diaphragm muscle fibres from healthy rats subjected to five or 10 days of MV + NMBA to simulate ICU treatment without underlying confounding pathology (like sepsis). Rats received daily treatment of either Prednisolone, VBP-15, BGP-15 or none. Myosin-II SHG signal intensities, fibre diameters (FD) as well as the parameters of myofibrillar angular parallelism (cosine angle sum, CAS) and in-register of adjacent myofibrils (Vernier density, VD) were computed from SHG images. ICU treatment caused a decline in FD at day 10 as well as a significant decline in CAS and VD from day 5. Vamorolone effectively recovered FD at day 10, while BGP-15 was more effective at day 5. BGP-15 was more effective than VBP-15 in recovering CAS at day 10 although not to control levels. In-register VD levels were restored at day 10 by both compounds. Our study is the first to provide quantitative insights into VIDD-related myofibrillar remodeling unravelled by SHG imaging, suggesting that both VBP-15 and BGP-15 can effectively ameliorate the structure-related dysfunction in VIDD

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring.

PURPOSE: The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. PARTICIPANTS: IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. FINDINGS TO DATE: The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. FUTURE PLANS: We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts

Geometry Reconstruction from Noisy Data using a Radial Basis Function Partition of Unity Method

International audienceManual three-dimensional segmentation of medical images results in noisy data sets representing three-dimensional objects. Based on this data, we look at how to perform a smooth object reconstruction. In particular, we are interested in the diaphragm, which is a thin curved volume. We use a partition of unity method where local object representations in each patch are blended into a global reconstruction. We use principal component analysis of the local data to align the local approximations with the data. Patches are adaptively refined based on local curvature. Due to the independence of the local approximations, we can increase the resolution in the thin dimension locally in each patch. We use infinitely smooth radial basis functions (RBF) to form a level set function with the object surface as its zero level set. Least squares approximation of the location, gradients, and values outside the object is employed to handle the noise in the data set. We evaluate the resulting reconstruction in terms of residual with respect to the initial data, local curvature, and visual appearance. We present guidelines for how to choose the method parameters, and investigate how they affect the result

Meshfree Simulation of Human Respiratory Muscles

International audienceThe main objective of our research is to understand the functionality of a human diaphragm, the main muscle of the respiratory system. Its action affects the volume of the thorax cavity such that the lungs can inflate and deflate, enabling a human to breathe. The aim is to enable medical researchers to perform studies on ventilator induced diaphragm disease (VIDD). The diaphragm models in the existing simulation tools are not advanced enough to capture the processes that lead to VIDD. Our model is based on the nonlinear elasticity equations. The goal is to solve the equations on a 3D diaphragm geometry. That can exhibit some numerical difficulties related to the small thickness of the tissue, compared to the overall size of the muscle. Localized radial basis function methods are chosen to discretize the equations in space and the quasistatic approach is used to advance the movement of the diaphragm in time. In this talk we will present the results of our first steps. These include the solutions of the static linear elasticity equations on a simple thin-plate geometry and also the full diaphragm geometry

Meshfree Simulation of Human Respiratory Muscles

International audienceThe main objective of our research is to understand the functionality of a human diaphragm, the main muscle of the respiratory system. Its action affects the volume of the thorax cavity such that the lungs can inflate and deflate, enabling a human to breathe. The aim is to enable medical researchers to perform studies on ventilator induced diaphragm disease (VIDD). The diaphragm models in the existing simulation tools are not advanced enough to capture the processes that lead to VIDD. Our model is based on the nonlinear elasticity equations. The goal is to solve the equations on a 3D diaphragm geometry. That can exhibit some numerical difficulties related to the small thickness of the tissue, compared to the overall size of the muscle. Localized radial basis function methods are chosen to discretize the equations in space and the quasistatic approach is used to advance the movement of the diaphragm in time. In this talk we will present the results of our first steps. These include the solutions of the static linear elasticity equations on a simple thin-plate geometry and also the full diaphragm geometry

Response to normobaric hypoxia in slow and fast muscles of the rat.

In this study the HIF-1 signaling pathway was comparatively studied in fast (EDL) and slow (soleus) muscles in basal normoxic conditions and under normobaric hypoxia (10% oxygen). In normoxia HIF-1\u3b1 transcription was determined by Real Time PCR and found similar in EDL and in soleus, whereas HIF-1\u3b1 dependent transcription, explored by Real Time PCR of VEGF which is known as a HIF-1\u3b1 regulated gene and by expression of luciferase under control of a HIF1\u3b1 responsive promoter, was higher in soleus than in EDL muscle. Under normobaric hypoxia conditions, HIF1\u3b1 mRNA showed a small but significant increase in both EDL and soleus and this change was accompanied by an increase of both VEGF transcription and luciferase expression. Interestingly, the time course of the response VEGF and luciferase to hypoxia was different in EDL compared to soleus and, in addition, some discrepancy was detected between VEGF and luciferase pattern. Taken together the results point to diversity between fast and slow muscles in the HIF-1\u3b1 signaling pathway both in normoxic and hypoxic conditions