Biomechanical pregnant pelvic system model and numerical simulation of childbirth: impact of delivery on the uterosacral ligaments, preliminary results.

INTRODUCTION AND HYPOTHESIS: We created a pregnant woman pelvic model to perform a simulation of delivery to understand the pathophysiology of urogenital prolapse by studying the constraints on the pelvic components (muscles, ligaments, pelvic organs) during childbirth. These simulations will also provide valuable tools to understand and teach obstetrical mechanics. METHODS: We built a numerical model of the pelvic system from a term pregnant woman, using the finite element method on a mesh built from magnetic resonance images of a nulliparous pregnant woman. Mechanical properties of pelvic tissues already determined by the team were adapted to account for pregnancy. RESULTS: The system allows delivery to be simulated. When a fetal head at the 50th percentile for the term goes through the pelvic system, uterosacral ligaments undergo a deformation of around 30 %. Uterosacral ligaments are the major pelvic sustaining structures, their lesion may be a potential cause of urogenital prolapse. We built a model of childbirth as a function of pregnancy term by varying volumes of fetal head and uterus. The impact on uterosacral ligaments is higher when the fetal head is larger. CONCLUSIONS: Our modelling is rather complete considering that it involves many organs including ligaments. It allows us to analyse the effect of childbirth on uterosacral ligaments and to understand how they impact on pelvic statics. First results are promising, but optimisation and future simulations will be needed. We also plan to simulate various delivery scenarios (cephalic, breech presentation, instrumental extraction), which will be useful to study perineal lesions and also to teach obstetrical mechanics.

SOFA--an open source framework for medical simulation.

SOFA is a new open source framework primarily targeted at medical simulation research. Based on an advanced software architecture, it allows to (1) create complex and evolving simulations by combining new algorithms with algorithms already included in SOFA; (2) modify most parameters of the simulation--deformable behavior, surface representation, solver, constraints, collision algorithm, etc.--by simply editing an XML file; (3) build complex models from simpler ones using a scene-graph description; (4) efficiently simulate the dynamics of interacting objects using abstract equation solvers; and (5) reuse and easily compare a variety of available methods. In this paper we highlight the key concepts of the SOFA architecture and illustrate its potential through a series of examples.

Blood vessel modeling for interactive simulation of interventional neuroradiology procedures.

Endovascular interventions can benefit from interactive simulation in their training phase but also during pre-operative and intra-operative phases if simulation scenarios are based on patient data. A key feature in this context is the ability to extract, from patient images, models of blood vessels that impede neither the realism nor the performance of simulation. This paper addresses both the segmentation and reconstruction of the vasculature from 3D Rotational Angiography data, and adapted to simulation: An original tracking algorithm is proposed to segment the vessel tree while filtering points extracted at the vessel surface in the vicinity of each point on the centerline; then an automatic procedure is described to reconstruct each local unstructured point set as a skeleton-based implicit surface (blobby model). The output of successively applying both algorithms is a new model of vasculature as a tree of local implicit models. The segmentation algorithm is compared with Multiple Hypothesis Testing (MHT) algorithm (Friman et al., 2010) on patient data, showing its greater ability to track blood vessels. The reconstruction algorithm is evaluated on both synthetic and patient data and demonstrate its ability to fit points with a subvoxel precision. Various tests are also reported where our model is used to simulate catheter navigation in interventional neuroradiology. An excellent realism, and much lower computational costs are reported when compared to triangular mesh surface models.

New approaches to catheter navigation for interventional radiology simulation.

For over 20 years, interventional methods have improved the outcomes of patients with cardiovascular disease. However, these procedures require an intricate combination of visual and tactile feedback and extensive training. In this paper, we describe a series of novel approaches that have led to the development of a high-fidelity simulation system for interventional neuroradiology. In particular, we focus on a new approach for real-time deformation of devices such as catheters and guidewires during navigation inside complex vascular networks. This approach combines a real-time incremental Finite Element Model (FEM), an optimization strategy based on substructure decomposition, and a new method for handling collision response in situations where the number of contact points is very large. We also briefly describe other aspects of the simulation system, from patient-specific segmentation to the simulation of contrast agent propagation and fast volume-rendering techniques for generating synthetic X-ray images in real time. Although currently targeted at stroke therapy, our results are applicable to the simulation of any interventional radiology procedure.

p53 induction prevents accumulation of aberrant transcripts in cancer cells.

Loss of fidelity of the splicing process occurs during tumor progression and can have a deleterious effect on genes like tumor suppressor genes. It was reported recently that the presence of aberrant transcripts of the TSG101 gene in breast cancer cells was associated with the mutation of the p53 tumor suppressor gene. On the basis of this observation, we have analyzed TSG101 transcript patterns in p53-active and p53-inactive cells. Using several isogenic cellular models, we demonstrate that the induction of p53 in cancer cells leads to a significant decrease of aberrant transcripts levels. This indicates a novel implication of p53 in the regulation of the splicing process.

Absence of p53-dependent induction of the metastatic suppressor KAI1 gene after DNA damage.

The p53 tumor suppressor protein functions to monitor the integrity of the genome. If a damage is detected, p53 binds tightly to specific sequence elements in the DNA and induces the transactivation of genes involved in various growth regulatory processes such as cell cycle progression, DNA repair and apoptosis. A p53-binding site was recently identified in the promoter region of the metastatic suppressor KAI1 gene, suggesting that this gene was a direct transcriptional target of p53. To test the relevance of this hypothesis, we studied the endogenous KAI1 expression in a series of human cell lines with varying p53 status in response to genotoxic treatment as well as in different cellular models exhibiting an inducible p53 activity. Overall, our data indicate that KAI1 expression is not significantly modulated by p53. This observation provides a direct evidence that the presence of a p53-binding site in regulatory domains is not a sufficient criteria to define a p53-transcriptional target gene.

[Localization of a tumor suppressor gene distal to D22S270 in colorectal cancers]. / Localisation d'un gène suppresseur de tumeur distal à D22S270 dans les cancers colorectaux.

Recurrent allelic losses on chromosome 22q have been reported in colorectal cancer, distal to the NF2 gene, suggesting that another tumor suppressor gene might be involved. We report here the typing of 256 sporadic colorectal tumors and 18 colonic cancer cell lines using a set of chromosome 22 polymorphisms, ranging from 20 to 45. A panel of somatic cell hybrids, that allows to distinguish 11 bins in the 22q13 region, was used to localize 19 of the 45 selected markers and the putative tumor suppressor gene BZRP. Allelic-loss was observed in 43% of tumors. The minimal region of deletion that could be determined, telomeric to locus D22S270, refines significantly the position of the gene. The localization of the BZRP gene in this region led to a systematic screening for somatic point mutation. Direct sequencing of its coding sequence in 36 tumors hemizygous for chromosome 22 allowed the identification of three polymorphisms but failed to detect somatic mutation.

Constraint-Based Haptic Rendering of Multirate Compliant Mechanisms.

The paper is dedicated to haptic rendering of complex physics-based environment in the context of surgical simulation. A new unified formalism for modeling the mechanical interactions between medical devices and anatomical structures and for computing accurately the haptic force feedback is presented. The approach deals with the mechanical interactions using appropriate force and/or motion transmission models named compliant mechanisms. These mechanisms are formulated as a constraint-based problem that is solved in two separate threads running at different frequencies. The first thread processes the whole simulation including the soft-tissue deformations, whereas the second one only deals with computer haptics. This method builds a bridge between the so-called virtual mechanisms (that were proposed for haptic rendering of rigid bodies) and intermediate representations (used for rendering of complex simulations). With this approach, it is possible to describe the specific behavior of various medical devices while relying on a unified method for solving the mechanical interactions between deformable objects and haptic rendering. The technique is demonstrated in interactive simulation of flexible needle insertion through soft anatomical structures with force feedback.

New approaches to catheter navigation for interventional radiology simulation.

For over 20 years, interventional methods have improved the outcomes of patients with cardiovascular disease. However, these procedures require an intricate combination of visual and tactile feedback and extensive training periods. In this paper, we describe a series of novel approaches that have lead to the development of a high-fidelity simulation system for interventional neuroradiology. In particular we focus on a new approach for real-time deformation of devices such as catheters and guidewires during navigation inside complex vascular networks. This approach combines a real-time incremental Finite Element Model, an optimization strategy based on substructure decomposition, and a new method for handling collision response in situations where the number of contacts points is very large. We also briefly describe other aspects of the simulation system, from patient-specific segmentation to the simulation of contrast agent propagation and fast volume rendering techniques for generating synthetic X-ray images in real-time.

BTG gene expression in the p53-dependent and -independent cellular response to DNA damage.

Exposure of mammalian cells to genotoxic agents evokes a complex cellular response. An ordered series of molecular events is necessary to sense DNA damage, transduce the signal, and ultimately delay the cell cycle or trigger apoptosis. Recently, we have shown that BTG2/TIS21 gene expression was induced in response to DNA damage through a p53-dependent pathway. This gene belongs to a newly identified family of structurally related genes whose other known human members are BTG1, BTG3, and Tob. To define the respective involvement of these four related genes in the cellular response to DNA damage, we studied their expression in human cell lines after a variety of genotoxic treatments. Our results demonstrated that were BTG1, BTG2/TIS21, and Tob genes the DNA damage--inducible genes. However, BTG2/TIS21 appeared to be the only p53-transcriptional target gene. We speculate that BTG proteins may play a coordinate role in a general transduction pathway that is induced in response to DNA damage. It has been previously described that recombinant BTG1 and BTG2/TIS21 can physically interact with PRMT1, an arginine methyl transferase, suggesting that BTG1 and BTG2/TIS21 induction may lead to posttranslational modifications of cellular proteins. In support of this hypothesis, we showed that the endogenous induction of BTG1 and BTG2 after genotoxic treatment was correlated with a modulation of protein methylation.

[Diagnostic and therapeutic problems in anencephaly]. / Problèmes diagnostiques et thérapeutiques posés par l'anencéphalie.

The authors report on 18 cases of anencephalus, studied from April, 1976 to December, 1982. Possible etiologies, morphological characteristics, circumstances leading to its discovery, and diagnostic tools are presented. Emphasis is placed on the usefulness of ultrasonography to diagnose this condition as early as the 13th to 14th week of gestation. Evacuation of the uterus is always difficult as it involves a second trimester abortion, but is one of the best indications for the use of prostaglandins. In a woman with a previous history of an anencephalic child, careful monitoring of subsequent pregnancies is necessary as the recurrence rate is approximately 4 p. 100 (13 p. 100 in the case of a second anencephalic child). Dosing of alpha-fetoprotein and acetylcholinesterase in amniotic fluid and repeated sonograms are indispensable.