Modeling and Real-Time Simulation of a Vascularized Liver Tissue

International audienceIn Europe only, about 100,000 deaths per year are related to cirrhosis or liver cancer. While surgery remains the option that offers the foremost success rate against such pathologies, several limitations still hinder its widespread development. Among the limiting factors is the lack of accurate planning systems, which has been a motivation for several recent works, aiming at better resection planning and training systems, relying on pre-operative imaging, anatomical and biomechanical modelling. While the vascular network in the liver plays a key role in defining the operative strategy, its influence at a biomechanical level has not been taken into account. In the paper we propose a real-time model of vascularized organs such as the liver. The model takes into account separate constitutive laws for the parenchyma and vessels, and defines a coupling mechanism between these two entities. In the evaluation section, we present results of in vitro porcine liver experiments that indicate a significant influence of vascular structures on the mechanical behaviour of tissue. We confirm the val- ues obtained in the experiments by computer simulation using standard FEM. Finally, we show that the conventional modelling approach can be efficiently approximated with the proposed composite model capable of real-time calculations

Image-guided Simulation of Heterogeneous Tissue Deformation For Augmented Reality during Hepatic Surgery

International audienceThis paper presents a method for real-time augmentation of vas- cular network and tumors during minimally invasive liver surgery. Internal structures computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Com- pared to state-of-the-art methods, our method uses a real-time biomechanical model to compute a volumetric displacement field from partial three-dimensional liver surface motion. This permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Real-time augmentation results are presented on in vivo and ex vivo data and illustrate the benefits of such an approach for minimally invasive surgery

Image-guided Simulation of Heterogeneous Tissue Deformation For Augmented Reality during Hepatic Surgery

International audienceThis paper presents a method for real-time augmentation of vas- cular network and tumors during minimally invasive liver surgery. Internal structures computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Com- pared to state-of-the-art methods, our method uses a real-time biomechanical model to compute a volumetric displacement field from partial three-dimensional liver surface motion. This permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Real-time augmentation results are presented on in vivo and ex vivo data and illustrate the benefits of such an approach for minimally invasive surgery

Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives.

Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug-body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms

Impact of Soft Tissue Heterogeneity on Augmented Reality for Liver Surgery

International audienceThis paper presents a method for real-time augmented reality of internal liver structures during minimally invasive hepatic surgery. Vessels and tumors computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Compared to current methods, our method is able to locate the in-depth positions of the tumors based on partial three-dimensional liver tissue motion using a real-time biomechanical model. This model permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Experimentations conducted on phantom liver permits to measure the accuracy of the augmentation while real-time augmentation on in vivo human liver during real surgery shows the benefits of such an approach for minimally invasive surgery

A dynamic magnetic shift method to increase nanoparticle concentration in cancer metastases: a feasibility study using simulations on autopsy specimens

A nanoparticle delivery system termed dynamic magnetic shift (DMS) has the potential to more effectively treat metastatic cancer by equilibrating therapeutic magnetic nanoparticles throughout tumors. To evaluate the feasibility of DMS, histological liver sections from autopsy cases of women who died from breast neoplasms were studied to measure vessel number, size, and spatial distribution in both metastatic tumors and normal tissue. Consistent with prior studies, normal tissue had a higher vascular density with a vessel-to-nuclei ratio of 0.48 ± 0.14 (n = 1000), whereas tumor tissue had a ratio of 0.13 ± 0.07 (n = 1000). For tumors, distances from cells to their nearest blood vessel were larger (average 43.8 μm, maximum 287 μm, n ≈ 5500) than normal cells (average 5.3 μm, maximum 67.8 μm, n ≈ 5500), implying that systemically delivered nanoparticles diffusing from vessels into surrounding tissue would preferentially dose healthy instead of cancerous cells. Numerical simulations of magnetically driven particle transport based on the autopsy data indicate that DMS would correct the problem by increasing nanoparticle levels in hypovascular regions of metastases to that of normal tissue, elevating the time-averaged concentration delivered to the tumor for magnetic actuation versus diffusion alone by 1.86-fold, and increasing the maximum concentration over time by 1.89-fold. Thus, DMS may prove useful in facilitating therapeutic nanoparticles to reach poorly vascularized regions of metastatic tumors that are not accessed by diffusion alone

Organ-on-a-Chip systems for new drugs development

Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies