Towards the in vivo mechanical characterization of abdominal wall in animal model: application to hernia repair

El trabajo presentado en esta tesis se centra en el diseño e implementación de una metodología que permita caracterizar in vivo el comportamiento mecánico pasivo de la pared abdominal. Esta metodología permitiría a los cirujanos disponer de información mecánica relevante sobre un paciente especí co, lo que podría contribuir a mejorar el tratamiento quirúrgico de hernias mediante malla protésica. El tratamiento quirúrgico de hernias consiste en cerrar la debilidad creada en el músculo, ya sea directamente con puntos de sutura o mediante la implantación de una malla protésica. En el caso de la malla, ésta es la responsable de absorber las tensiones a las que el músculo se ve sometido durante el tiempo en el que se produce la regeneración de tejido. Para reducir el riego de aparición de dolor postoperatorio, rotura o rasgadura de tejido o incluso una recidiva, la malla debe mimetizar la respuesta mecánica de la zona de la pared donde vaya a ser colocada, que a su vez puede variar de un paciente a otro en función de su edad, género, índice de masa corporal u otras características físicas. Un mejor conocimiento de las propiedades mecánicas del abdomen en paciente especí co ayudaría al cirujano a determinar qué malla protésica se puede considerar la ideal, mecánicamente hablando. Por todo ello, el trabajo que aquí se presenta plantea una aproximación in vivo para caracterizar la pared abdominal sobre un modelo animal y su posterior implementación en casos de patologías herniarias. En un primer paso, se ha realizado un estudio biomecánico del cierre en línea alba, que ayudase a entender los aspectos mecánicos y biológicos que tienen lugar durante la curación de la herida a corto y largo plazo. A continuación, se han llevado a cabo ensayos mecánicos de in ado sobre la pared, que combinados con el uso de cámaras y técnicas de adquisición de imagen han permitido extraer la respuesta del tejido de una manera no invasiva. Este estudio experimental, se ha llevado a cabo sobre especímenes sanos y otro herniados y reparados con distintas mallas quirúrgicas, lo que ha permitido extrapolar el efecto in vivo que provocan estas mallas. A partir de los datos experimentales también se ha desarrollado un análisis numérico que permitiese caracterizar la respuesta mecánica especí ca de cada espécimen. A este efecto, dicha caracterización se ha tratado como un problema inverso y resuelto primeramente mediante un análisis de super cies de respuesta y después con un algoritmo propio aplicado a modelos hiperelásticos. Finalmente, también se ha reconstruido un modelo de elementos nitos de la cavidad abdominal que permite simular el efecto producido por distintas mallas protésicas así como su alteración respecto al tejido sano

A 3D multi-scale skeletal muscle model to predict active and passive responses. Application to intra-abdominal pressure prediction

Computational models have been used extensively to study the behavior of skeletal muscle structures, however few of these models are able to evaluate their 3D active response using as input experimental measurements such as electromyography. Hence, improving the activation mechanisms in simulation models can provide interesting and useful achievements in this field. Therefore, the purpose of this paper was to develop a multi-scale chemo-mechanical material model to consider the active behavior of skeletal muscle in 3D geometries. The model was used to investigate the response of abdominal muscles which represent a challenging scenario due to their complex geometry and anatomical conditions. Realistic muscle geometries and other tissues of the human abdomen, including transverse abdominis (TA), internal oblique (IO), external oblique (EO), rectus abdominis (RA), rectus sheath (RSH), linea alba (LA) and aponeurosis (APO) were considered. Since the geometry of these tissues was obtained from magnetic resonance images, an iterative algorithm was implemented to find the initial stress state that achieve the equilibrium of them with the intra-abdominal pressure. In order to investigate the functionality of the proposed model, the increase of intra-abdominal pressure was calculated during cough in the supine position while the Ca2+ signal for activating the muscles was set in regard to experimentally recorded electrical activity from previous studies. The amount of intra-abdominal pressure calculated by the model is consistent with reported experimental results. This model can serve as a virtual laboratory to analyze the role of the abdominal wall components in different conditions, such as the performance of meshes used for repairing hernia defects

Mechanical modelling of the abdominal wall and biomaterials for hernia surgery

Abdominal surgery for hernia repair is based on the implantation of a synthetic mesh in the defect area which aims at reinforcing the damaged wall. This clinical intervention is common in today's society and, in unfavorable cases such as obese patients or patients with large defects, could lead to a number of problems that reduce the quality of life of patients. The most common problems are the appearance of fibrosis, the hernia recurrence and occurrence of abdominal discomfort due to poor compliance between the host tissue and the prosthesis. Currently, surgeons have no definitive and universally accepted guidelines for the selection of the appropriate prosthesis for each patient and type of defect. Therefore, the choice of one or another mesh, and their placement in case of anisotropic meshes, is a decision to be taken by the surgeons according to their experience. This thesis aims to study the abdominal hernia surgery from the continuum mechanics point of view. However, for the supply and validation of the generated models, it is necessary to perform an experimental study in an animal model. Since this is a multidisciplinary problem, the study approached was developed in collaboration with the Translational Research Group in Biomaterials and Tissue Engineering at the University of Alcalá de Henares (Madrid). The final goal of hernia surgery is that the prosthesis ensures adequate tissular integration, being capable, among other things, to reproduce the mechanical behaviour of the healthy abdominal wall and to absorb the stresses due to the physiological loads to which the abdomen is subjected. Therefore, in addition to addressing the study in animal models to analyze the integration on the wall, the mechanical modelling of the abdominal wall and the biomaterials used in hernia repair is essential. For this, the construction of an ``in silico'' model of the human abdomen has been developed. Due to the diversity of commercial products on the market, this thesis focusses on the study of three representative prostheses, specifically Surgipro, Optilene and Infinit. These meshes are characterized by different geometric parameters and are made of different materials. In this work, the mechanical properties of the prostheses have been determined experimentally and different constitutive models, that reproduce the patterns of the mechanical behaviour observed in both, the abdominal muscle and implanted biomaterials, have been proposed. Specifically, the numerical modelling of the response of the abdominal muscle, including both active and passive responses, and prostheses have been approached within the framework of the nonlinear hyperelasticity in large deformations. The latter approach of this thesis aims to model, using the finite element method, the mechanical response of the wall with the implanted mesh. A complete model of the human abdomen has been defined from nuclear magnetic resonance imaging. This complete model allows differentiating the main anatomical units of the abdomen and it is used to simulate the passive and active responses. Furthermore, this model allows the study of the response of the healthy wall and the analysis of the final mechanical response of the herniated human abdomen to the placement of different prostheses. In summary, this thesis establishes a methodology to the automation of computational models for personalized surgical procedures in order to select the most appropriate mesh for each patient as well as the appropriate placement on the defect in the case of anisotropic prostheses

Towards the mechanical characterization of abdominal wall by inverse analysis

The aim of this study is to characterize the passive mechanical behaviour of abdominal wall in vivo in an animal model using only external cameras and numerical analysis. The main objective lies in defining a methodology that provides in vivo information of a specific patient without altering mechanical properties. It is demonstrated in the mechanical study of abdomen for hernia purposes. Mechanical tests consisted on pneumoperitoneum tests performed on New Zealand rabbits, where inner pressure was varied from 0 mmHg to 12 mmHg. Changes in the external abdominal surface were recorded and several points were tracked. Based on their coordinates we reconstructed a 3D finite element model of the abdominal wall, considering an incompressible hyperelastic material model defined by two parameters. The spatial distributions of these parameters (shear modulus and non linear parameter) were calculated by inverse analysis, using two different types of regularization: Total Variation Diminishing (TVD) and Tikhonov (H1). After solving the inverse problem, the distribution of the material parameters were obtained along the abdominal surface. Accuracy of the results was evaluated for the last level of pressure. Results revealed a higher value of the shear modulus in a wide stripe along the craneo-caudal direction, associated with the presence of linea alba in conjunction with fascias and rectus abdominis. Non linear parameter distribution was smoother and the location of higher values varied with the regularization type. Both regularizations proved to yield in an accurate predicted displacement field, but H1 obtained a smoother material parameter distribution while TVD included some discontinuities. The methodology here presented was able to characterize in vivo the passive non linear mechanical response of the abdominal wall

Virtual reality training and assessment in laparoscopic rectum surgery

Background: Virtual-reality (VR) based simulation techniques offer an efficient and low cost alternative to conventional surgery training. This article describes a VR training and assessment system in laparoscopic rectum surgery. Methods: To give a realistic visual performance of interaction between membrane tissue and surgery tools, a generalized cylinder based collision detection and a multi-layer mass-spring model are presented. A dynamic assessment model is also designed for hierarchy training evaluation. Results: With this simulator, trainees can operate on the virtual rectum with both visual and haptic sensation feedback simultaneously. The system also offers surgeons instructions in real time when improper manipulation happens. The simulator has been tested and evaluated by ten subjects. Conclusions: This prototype system has been verified by colorectal surgeons through a pilot study. They believe the visual performance and the tactile feedback are realistic. It exhibits the potential to effectively improve the surgical skills of trainee surgeons and significantly shorten their learning curve. © 2014 John Wiley & Sons, Ltd

Computational analysis of blood flow and stress patterns in the aorta of patients with Marfan syndrome

Personalised external aortic root support (PEARS) was designed to prevent progressive aortic dilatation, and the associated risk of aortic dissection, in patients with Marfan syndrome by providing an additional support to the aorta. The objective of this thesis was to understand the biomechanical implications of PEARS surgery as well as to investigate the altered haemodynamics associated with the disease and its treatment. Finite element (FE) models were developed using patient-specific aortic geometries reconstructed from pre and post-PEARS magnetic resonance (MR) images of three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients’ pulse pressure was applied with a zero-displacement constraint at all boundaries. Results showed that peak aortic stresses and displacements before PEARS were located at the sinuses of Valsalva but following PEARS surgery, they were shifted to the aortic arch, at the intersection between the supported and unsupported aorta. The zero-displacement constraint at the aortic root was subsequently removed and replaced with downward motion measured from in vivo images. This revealed significant increases in the longitudinal wall stress, especially in the pre-PEARS models. Computational fluid dynamics (CFD) models were developed to evaluate flow characteristics. The correlation-based transitional Shear Stress Transport (SST-Tran) model was adopted to simulate potential transitional and turbulence flow during part of the cardiac cycle and flow waveforms derived from phase-contrast MR images were imposed at the inlets. Qualitative patterns of the haemodynamics were similar pre- and post-PEARS with variations in mean helicity flow index (HFI) of -10%, 35% and 20% in the post-PEARS aortas of the three patients. A fluid-structure interaction (FSI) model was developed for one patient, pre- and post-PEARS in order to examine the effect of wall compliance on aortic flow as well as the effect of pulsatile flow on wall stress. This model excluded the sinuses and was based on the laminar flow assumption. The results were similar to those obtained using the rigid wall and static structural models, with minor quantitative differences. Considering the higher computational cost of FSI simulations and the relatively small differences observed in peak wall stress, it is reasonable to suggest that static structural models would be sufficient for wall stress prediction. Additionally, aortic root motion had a more profound effect on wall stress than wall compliance. Further studies are required to assess the statistical significance of the findings outlined in this thesis. Recommendations for future work were also highlighted, with emphasis on model assumptions including material properties, residual stress and boundary conditions.Open Acces

Uncomplicated Acute Appendicitis – Studies on Diagnosis and Treatment Outcomes

ABSTRACT Appendectomy has been the indisputable treatment of acute appendicitis for over a century. Acute appendicitis has been evaluated to always progress to perforation. Current evidence suggests complicated and uncomplicated acute appendicitis to be different forms of the disease. Complicated appendicitis requires emergency appendectomy with the exception of a restricted periappendicular abscess. Evidence of the feasibility of antibiotic therapy in the treatment of uncomplicated acute appendicitis has been provided by several randomized trials and meta-analyses mainly investigating combinations of intravenous followed by peroral antibiotics. In addition to treatment success, we need to consider treatment costs and patient-centered factors in assessing all different treatment options. With the emerging possibility of nonoperative treatment, accurate diagnosis and differential diagnosis of the appendicitis severity is of vital importance. Computed tomography (CT) is the current gold standard in appendicitis diagnostics, but it is accurately criticized for ionizing radiation, especially with appendicitis patient population consisting of mainly young adults. Low-dose CT protocols have been developed to address this issue. This series of studies aimed at comparing overall treatment costs (Study I) and patient quality of life (QOL), satisfaction, and treatment preference (Study III) between appendectomy and antibiotic therapy. To assess the issue of CT radiation, a low-dose protocol was compared with standard CT in the OPTICAP trial (Study II). The APPAC II trial (Study IV) aimed at optimizing antibiotic therapy for uncomplicated acute appendicitis by comparing p.o. monotherapy with i.v. followed by p.o. antibiotics. The possibility of symptomatic treatment is visited in the APPAC III study protocol (Study V). The overall cost of antibiotic therapy was significantly lower compared to appendectomy with similar QOL, but the patient satisfaction was higher in the appendectomy group. The low-dose CT protocol had comparable diagnostic accuracy with standard CT with significantly less radiation. Treatment success of the peroral monotherapy was clinically comparable to intravenous followed by peroral in the treatment of uncomplicated acute appendicitis. KEYWORDS: acute appendicitis, antibiotics, appendectomy, computed tomography imaging, costs, quality of life, uncomplicated acute appendicitis.TIIVISTELMÄ Umpilisäkkeen poisto on ollut umpilisäketulehduksen hoito yli vuosisadan ajan. Umpilisäketulehduksen on aiemmin ajateltu johtavan aina umpilisäkkeen puhkeamiseen, mutta nykyään tunnistetaan erikseen lievä ja vaikea tautimuoto. Vaikea umpilisäketulehdus vaatii kiireellisen leikkaushoidon lukuun ottamatta umpilisäkkeen vieruskudoksen paisetta. Useat satunnaistetut tutkimukset ja meta-analyysit ovat osoittaneet, että lievempää muotoa voidaan turvallisesti ja tehokkaasti hoitaa suonensisäisten (i.v.) ja tablettimuotoisten (p.o.) antibioottien yhdistelmällä. Verrattaessa leikkaus- ja antibioottihoitoa toisiinsa tulee hoidon tehon lisäksi huomioida hoidon kustannukset ja potilaskohtaiset tekijät. Antibioottihoidon mahdollisuus korostaa lievän umpilisäketulehduksen oikean diagnoosin ja tautimuotojen erottamisen välttämättömyyttä. Tietokonekuvantaminen (TT) on diagnostiikan kultainen standardi, mutta sen ongelmana on säderasitus. Tämä korostuu umpilisäketulehduksen yhteydessä, koska potilaat ovat pääasiassa nuoria aikuisia, minkä vuoksi on kehitetty matala-annoksisia TT-kuvantamistapoja. Tämän tutkimuksen tavoitteena oli verrata leikkaus- ja antibioottihoidon kokonaiskustannuksia (Työ I) sekä potilaiden elämänlaatua ja tyytyväisyyttä (Työ III). Säderasituksen vähentämiseksi vertasimme matala-annoksista TT-kuvantamista standardiin TT-kuvantamiseen OPTICAP-tutkimuksessa (Työ II). APPAC II-tutkimuksessa vertasimme p.o. antibioottia i.v. ja p.o. antibiootin yhdistelmään antibioottihoidon optimoimiseksi (Työ IV). Oireenmukaisen hoidon mahdollisuutta arvioitiin suunnittelemalla lumekontrolloitu APPAC III -tutkimus (Työ V). Antibioottihoidon kustannukset olivat leikkaushoitoa merkittävästi alhaisemmat eikä potilaiden elämänlaadussa ollut eroa, mutta leikatut potilaat olivat tyytyväisempiä saamaansa hoitoon. Matala-annoksisen TT:n diagnostinen tarkkuus vastasi standardia TT:tä merkittävästi alhaisemmalla säderasituksella. Lievän umpilisäketulehduksen hoidossa p.o. antibiootti oli kliinisesti yhtä tehokas kuin i.v. ja p.o. hoidon yhdistelmä. AVAINSANAT: akuutti umpilisäketulehdus, antibiootti, elämänlaatu, kulut, lievä umpilisäketulehdus, umpilisäkkeen poisto, tietokonekuvantamine