In vivo measurement of human brain elasticity using a light aspiration device

The brain deformation that occurs during neurosurgery is a serious issue impacting the patient "safety" as well as the invasiveness of the brain surgery. Model-driven compensation is a realistic and efficient solution to solve this problem. However, a vital issue is the lack of reliable and easily obtainable patient-specific mechanical characteristics of the brain which, according to clinicians' experience, can vary considerably. We designed an aspiration device that is able to meet the very rigorous sterilization and handling process imposed during surgery, and especially neurosurgery. The device, which has no electronic component, is simple, light and can be considered as an ancillary instrument. The deformation of the aspirated tissue is imaged via a mirror using an external camera. This paper describes the experimental setup as well as its use during a specific neurosurgery. The experimental data was used to calibrate a continuous model. We show that we were able to extract an in vivo constitutive law of the brain elasticity: thus for the first time, measurements are carried out per-operatively on the patient, just before the resection of the brain parenchyma. This paper discloses the results of a difficult experiment and provide for the first time in-vivo data on human brain elasticity. The results point out the softness as well as the highly non-linear behavior of the brain tissue.Comment: Medical Image Analysis (2009) accept\'

The Invalidity of the Laplace Law for Biological Vessels and of Estimating Elastic Modulus from Total Stress vs. Strain: a New Practical Method

The quantification of the stiffness of tubular biological structures is often obtained, both in vivo and in vitro, as the slope of total transmural hoop stress plotted against hoop strain. Total hoop stress is typically estimated using the "Laplace law." We show that this procedure is fundamentally flawed for two reasons: Firstly, the Laplace law predicts total stress incorrectly for biological vessels. Furthermore, because muscle and other biological tissue are closely volume-preserving, quantifications of elastic modulus require the removal of the contribution to total stress from incompressibility. We show that this hydrostatic contribution to total stress has a strong material-dependent nonlinear response to deformation that is difficult to predict or measure. To address this difficulty, we propose a new practical method to estimate a mechanically viable modulus of elasticity that can be applied both in vivo and in vitro using the same measurements as current methods, with care taken to record the reference state. To be insensitive to incompressibility, our method is based on shear stress rather than hoop stress, and provides a true measure of the elastic response without application of the Laplace law. We demonstrate the accuracy of our method using a mathematical model of tube inflation with multiple constitutive models. We also re-analyze an in vivo study from the gastro-intestinal literature that applied the standard approach and concluded that a drug-induced change in elastic modulus depended on the protocol used to distend the esophageal lumen. Our new method removes this protocol-dependent inconsistency in the previous result.Comment: 34 pages, 13 figure

Anisotropic behaviour of human gallbladder walls

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel–Gasser–Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder

A coupled mitral valve -- left ventricle model with fluid-structure interaction

Understanding the interaction between the valves and walls of the heart is important in assessing and subsequently treating heart dysfunction. With advancements in cardiac imaging, nonlinear mechanics and computational techniques, it is now possible to explore the mechanics of valve-heart interactions using anatomically and physiologically realistic models. This study presents an integrated model of the mitral valve (MV) coupled to the left ventricle (LV), with the geometry derived from in vivo clinical magnetic resonance images. Numerical simulations using this coupled MV-LV model are developed using an immersed boundary/finite element method. The model incorporates detailed valvular features, left ventricular contraction, nonlinear soft tissue mechanics, and fluid-mediated interactions between the MV and LV wall. We use the model to simulate the cardiac function from diastole to systole, and investigate how myocardial active relaxation function affects the LV pump function. The results of the new model agree with in vivo measurements, and demonstrate that the diastolic filling pressure increases significantly with impaired myocardial active relaxation to maintain the normal cardiac output. The coupled model has the potential to advance fundamental knowledge of mechanisms underlying MV-LV interaction, and help in risk stratification and optimization of therapies for heart diseases.Comment: 25 pages, 6 figure

A 3D discrete model of the diaphragm and human trunk

In this paper, a 3D discrete model is presented to model the movements of the trunk during breathing. In this model, objects are represented by physical particles on their contours. A simple notion of force generated by a linear actuator allows the model to create forces on each particle by way of a geometrical attractor. Tissue elasticity and contractility are modeled by local shape memory and muscular fibers attractors. A specific dynamic MRI study was used to build a simple trunk model comprised of by three compartments: lungs, diaphragm and abdomen. This model was registered on the real geometry. Simulation results were compared qualitatively as well as quantitatively to the experimental data, in terms of volume and geometry. A good correlation was obtained between the model and the real data. Thanks to this model, pathology such as hemidiaphragm paralysis can also be simulated.Comment: published in: "Lung Modelling", France (2006

Determining the Biomechanical Behavior of the Liver Using Medical Image Analysis and Evolutionary Computation

Modeling the liver deformation forms the basis for the development of new clinical applications that improve the diagnosis, planning and guidance in liver surgery. However, the patient-specific modeling of this organ and its validation are still a challenge in Biomechanics. The reason is the difficulty to measure the mechanical response of the in vivo liver tissue. The current approach consist of performing minimally invasive or open surgery aimed at estimating the elastic constant of the proposed biomechanical models. This dissertation presents how the use of medical image analysis and evolutionary computation allows the characterization of the biomechanical behavior of the liver, avoiding the use of these minimally invasive techniques. In particular, the use of similarity coefficients commonly used in medical image analysis has permitted, on one hand, to estimate the patient-specific biomechanical model of the liver avoiding the invasive measurement of its mechanical response. On the other hand, these coefficients have also permitted to validate the proposed biomechanical models. Jaccard coefficient and Hausdorff distance have been used to validate the models proposed to simulate the behavior of ex vivo lamb livers, calculating the error between the volume of the experimentally deformed samples of the livers and the volume from biomechanical simulations of these deformations. These coefficients has provided information, such as the shape of the samples and the error distribution along their volume. For this reason, both coefficients have also been used to formulate a novel function, the Geometric Similarity Function (GSF). This function has permitted to establish a methodology to estimate the elastic constants of the models proposed for the human liver using evolutionary computation. Several optimization strategies, using GSF as cost function, have been developed aimed at estimating the patient-specific elastic constants of the biomechanical models proposed for the human liver. Finally, this methodology has been used to define and validate a biomechanical model proposed for an in vitro human liver.Martínez Martínez, F. (2014). Determining the Biomechanical Behavior of the Liver Using Medical Image Analysis and Evolutionary Computation [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/39337TESI

Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload

Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as β-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and β-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7–9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders

In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.

Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter

Cavitation in soft matter

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field