A microscopic model of the dose distribution in hepatocellular carcinoma after selective internal radiation therapy.

The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images. METHODS: Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law. RESULTS: In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver. CONCLUSIONS: The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images.

Patient-specific biomechanical model of hypoplastic left heart to predict post-operative cardio-circulatory behaviour.

Hypoplastic left heart syndrome is a complex congenital heart disease characterised by the underdevelopment of the left ventricle normally treated with a three-stage surgical repair. In this study, a multiscale closed-loop cardio-circulatory model is created to reproduce the pre-operative condition of a patient suffering from such pathology and virtual surgery is performed. Firstly, cardio-circulatory parameters are estimated using a fully closed-loop cardio-circulatory lumped parameter model. Secondly, a 3D standalone FEA model is build up to obtain active and passive ventricular characteristics and unloaded reference state. Lastly, the 3D model of the single ventricle is coupled to the lumped parameter model of the circulation obtaining a multiscale closed-loop pre-operative model. Lacking any information on the fibre orientation, two cases were simulated: (i) fibre distributed as in the physiological right ventricle and (ii) fibre as in the physiological left ventricle. Once the pre-operative condition is satisfactorily simulated for the two cases, virtual surgery is performed. The post-operative results in the two cases highlighted similar hemodynamic behaviour but different local mechanics. This finding suggests that the knowledge of the patient-specific fibre arrangement is important to correctly estimate the single ventricle's working condition and consequently can be valuable to support clinical decision.

Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors.

Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilaginous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized.

Integrated Stent Models Based on Dimension Reduction: Review and Future Perspectives.

Stent modeling represents a challenging task from both the theoretical and numerical viewpoints, due to its multi-physics nature and to the complex geometrical configuration of these devices. In this light, dimensional model reduction enables a comprehensive geometrical and physical description of stenting at affordable computational costs. In this work, we aim at reviewing dimensional model reduction of stent mechanics and drug release. Firstly, we address model reduction techniques for the description of stent mechanics, aiming to illustrate how a three-dimensional stent model can be transformed into a collection of interconnected one-dimensional rods, called a "stent net". Secondly, we review available model reduction methods similarly applied to drug release, in which the "stent net" concept is adopted for modeling of drug elution. As a result, drug eluting stents are described as a distribution of concentrated drug release sources located on a graph that fully represents the stent geometry. Lastly, new results about the extension of these model reduction approaches to biodegradable stents are also discussed.

A multiscale model for the study of cardiac biomechanics in single-ventricle surgeries: a clinical case.

Complex congenital heart disease characterized by the underdevelopment of one ventricular chamber (single ventricle (SV) circulation) is normally treated with a three-stage surgical repair. This study aims at developing a multiscale computational framework able to couple a patient-specific three-dimensional finite-element model of the SV to a patient-specific lumped parameter (LP) model of the whole circulation, in a closed-loop fashion. A sequential approach was carried out: (i) cardiocirculatory parameters were estimated by using a fully LP model; (ii) ventricular material parameters and unloaded geometry were identified by means of the stand-alone, three-dimensional model of the SV; and (iii) the three-dimensional model of SV was coupled to the LP model of the circulation, thus closing the loop and creating a multiscale model. Once the patient-specific multiscale model was set using pre-operative clinical data, the virtual surgery was performed, and the post-operative conditions were simulated. This approach allows the analysis of local information on ventricular function as well as global parameters of the cardiovascular system. This methodology is generally applicable to patients suffering from SV disease for surgical planning at different stages of treatment. As an example, a clinical case from stage 1 to stage 2 is considered here.

Combined approach for the biomechanical characterization of skin lesions.

Melanocytic nevi are common benign skin lesions, known as moles, due to proliferation of melanocytes, the pigmented skin cells. The uncontrolled growth of these cells leads instead to cutaneous malignant melanoma, an aggressive tumour whose rate of survival dramatically increases if early diagnosis is provided. Alteration on the mechanical properties of the skin in presence of lesions has been assessed. In this context, we aim at developing a combined approach consisting of an experimental and a computational study to biomechanically characterize the skin and both malign and benign skin lesions (i.e., nevi and malignant melanoma). In particular, the former study is performed to evaluate the biomechanical response of the different skin layers after the application of a displacement field and relies on a multi-scale strategy, ranging from the tissue level to the cellular level. Computational models will be tuned against experimental data (e.g., confocal laser scanning microscopy data) to estimate the mechanical properties of the different layers of the skin and the skin lesions. In particular, the confocal laser scanning microscopy is able to provide non-invasive histomorphological analysis of skin in vivo. The integration of the experimental and the computational results will allow the evaluation of possible alterations of the local mechanical properties occurring in case of pathological condition.

Stent deformation, physical stress, and drug elution obtained with provisional stenting, conventional culotte and Tryton-based culotte to treat bifurcations: a virtual simulation study.

AIMS: This study sought to investigate the possible influence of different bifurcation stenting techniques on stent deformation, physical stress, and drug elution using a virtual tool that includes structural, fluid dynamics and drug-eluting numerical models. METHODS AND RESULTS: A virtual bench test based on explicit dynamics modelling was used to simulate procedures on bifurcated coronary vessels performed according to three different stenting techniques: provisional side branch stenting, culotte, and Tryton-based culotte. Geometrical configurations obtained after virtual stenting simulations were used to perform fluid dynamics and drug elution analyses. The results showed that substantially different patterns of mechanical deformation, shear stress and theoretical drug elution were obtained using the different techniques. Compared with conventional culotte, the dedicated Tryton seems to facilitate the intervention in terms of improved access to the main branch and to lower its biomechanical influence on the coronary bifurcation in terms of mechanical and haemodynamic parameters. However, since the Tryton stent is a bare metal stent, the drug elution obtained is lower. CONCLUSIONS: Numerical models might successfully complement the information on stenting procedures obtained with traditional approaches such as in vitro bench testing or clinical trials. Devices dedicated to bifurcations may facilitate procedure completion and may result in specific patterns of mechanical stress, regional blood flow and drug elution.

Drug delivery patterns for different stenting techniques in coronary bifurcations: a comparative computational study.

The treatment of coronary bifurcation lesions represents a challenge for the interventional cardiologists due to the lower rate of procedural success and the higher risk of restenosis. The advent of drug-eluting stents (DES) has dramatically reduced restenosis and consequently the request for re-intervention. The aim of the present work is to provide further insight about the effectiveness of DES by means of a computational study that combines virtual stent implantation, fluid dynamics and drug release for different stenting protocols currently used in the treatment of a coronary artery bifurcation. An explicit dynamic finite element model is developed in order to obtain realistic configurations of the implanted devices used to perform fluid dynamics analysis by means of a previously developed finite element method coupling the blood flow and the intramural plasma filtration in rigid arteries. To efficiently model the drug release, a multiscale strategy is adopted, ranging from lumped parameter model accounting for drug release to fully 3-D models for drug transport to the artery. Differences in drug delivery to the artery are evaluated with respect to local drug dosage. This model allowed to compare alternative stenting configurations (namely the Provisional Side Branch, the Culotte and the Inverted Culotte techniques), thus suggesting guidelines in the treatment of coronary bifurcation lesions and addressing clinical issues such as the effectiveness of drug delivery to lesions in the side branch, as well as the influence of incomplete strut apposition and overlapping stents.

A mechanical simulator of cardiac wall kinematics.

Aim of this study is to develop a mechanical simulator (MS) reproducing cardiac wall kinematics [i.e., radial (R), longitudinal (L) and rotational (RT) motions] to test piezoelectric gyroscopic sensors (GS) that are able to measure cardiac torsion that has proved to be a sensitive index of cardiac performance. The MS consists of three brushless motors controlled by a dedicated software either separately or simultaneously reproducing the three main cardiac wall movements (R, L, RT) obtained by implementing different physiologic or pathologic velocity profiles derived from in vivo data. GS accuracy (max % error) was experimentally tested by connecting it to the MS driven in velocity in different working conditions [i.e., cardiac period (515-1030 ms), RT angle (4-16 degrees), GS axis inclination (0-90 degrees) with respect to the cardiac rotation axis]. The MS reproduced the tested velocity profiles well. The GS showed high accuracy in measuring both physiologic and pathologic RT velocity profiles, whereas they proved insensitive to R and L motions. GS axis inclination influenced measurements; however, it was possible to correct this taking the inclination angle cosine into account. The MS proved to be a useful tool to study cardiac wall kinematics and test GS reliability with a view to in vivo application.