Gradient-induced vibrations and motion-induced Lenz effects on conductive nonmagnetic orthopedic implants in MRI.

Purpose: To quantify the extent of gradient-induced vibrations, and the magnitude of motion-induced displacement forces ("Lenz effect"), in conductive nonmagnetic orthopedic prostheses.

Methods: The investigation is carried out through numerical simulations, for a 3 T scanner. For gradient-induced torques and vibrations, a knee and a shoulder implant are considered, at dB/dt equal to 42 T/s (rms).

AST: An OpenSim-based tool for the automatic scaling of generic musculoskeletal models.

Background And Objectives: The paper introduces a tool called Automatic Scaling Tool (AST) designed for improving and expediting musculoskeletal (MSK) simulations based on generic models in OpenSim. Scaling is a crucial initial step in MSK analyses, involving the correction of virtual marker locations on a model to align with actual experimental markers.

Methods: The AST automates this process by iteratively adjusting virtual markers using scaling and inverse kinematics on a static trial.

Hip-spine relationship: clinical evidence and biomechanical issues.

The hip-spine relationship is a critical consideration in total hip arthroplasty (THA) procedures. While THA is generally successful in patient, complications such as instability and dislocation can arise. These issues are significantly influenced by the alignment of implant components and the overall balance of the spine and pelvis, known as spinopelvic balance.

Credibility assessment of computational models according to ASME V&V40: Application to the Bologna Biomechanical Computed Tomography solution.

Background And Objective: When a computational model aims to be adopted beyond research purposes, e.g. to inform a clinical or regulatory decision, trust must be placed in its predictive accuracy.

A Credibility Assessment Plan for an In Silico Model that Predicts the Dose-Response Relationship of New Tuberculosis Treatments.

Tuberculosis is one of the leading causes of death in several developing countries and a public health emergency of international concern. In Silico Trials can be used to support innovation in the context of drug development reducing the duration and the cost of the clinical experimentations, a particularly desirable goal for diseases such as tuberculosis. The agent-based Universal Immune System Simulator was used to develop an In Silico Trials environment that can predict the dose-response of new therapeutic vaccines against pulmonary tuberculosis, supporting the optimal design of clinical trials.

Experimental validation of a subject-specific finite element model of lumbar spine segment using digital image correlation.

Pathologies such as cancer metastasis and osteoporosis strongly affect the mechanical properties of the vertebral bone and increase the risk of fragility fractures. The prediction of the fracture risk with a patient-specific model, directly generated from the diagnostic images of the patient, could help the clinician in the choice of the correct therapy to follow. But before such models can be used to support any clinical decision, their credibility must be demonstrated through verification, validation, and uncertainty quantification.

Toward A Regulatory Pathway for the Use of in Silico Trials in the CE Marking of Medical Devices.

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic.

Using Musculoskeletal Models to Estimate Total Knee Replacement Kinematics and Loads: Effect of Differences Between Models.

Total knee replacement (TKR) is one of the most performed orthopedic surgeries to treat knee joint diseases in the elderly population. Although the survivorship of knee implants may extend beyond two decades, the poor outcome rate remains considerable. A recent computational approach used to better understand failure modes and improve TKR outcomes is based on the combination of musculoskeletal (MSK) and finite element models.

In silico re-foundation of strain-based healing assessment of fractures treated with an external fixator.

In the last decades, the literature has demonstrated a renewed interest in finding quantitative and non-invasive techniques for the assessment of bone fractures, by replacing X-ray images. Many different approaches have been proposed from ultrasounds to vibrations. This study aims to numerically assess the foundation of a method firstly proposed in 70' years, based on strain gauges measurements on external fixators for fracture healing monitoring.

Possible Contexts of Use for In Silico Trials Methodologies: A Consensus-Based Review.

The term "In Silico Trial" indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process.

Effect of Suboptimal Neuromuscular Control on the Risk of Massive Wear in Total Knee Replacement.

The optimal neuromuscular control (muscle activation strategy that minimises the consumption of metabolic energy) during level walking is very close to that which minimises the force transmitted through the joints of the lower limbs. Thus, any suboptimal control involves an overloading of the joints. Some total knee replacement patients adopt suboptimal control strategies during level walking; this is particularly true for patients with co-morbidities that cause neuromotor control degeneration, such as Parkinson's Disease (PD).

Verification of an agent-based disease model of human Mycobacterium tuberculosis infection.

Agent-based models (ABMs) are a powerful class of computational models widely used to simulate complex phenomena in many different application areas. However, one of the most critical aspects, poorly investigated in the literature, regards an important step of the model credibility assessment: solution verification. This study overcomes this limitation by proposing a general verification framework for ABMs that aims at evaluating the numerical errors associated with the model.

Generation of digital patients for the simulation of tuberculosis with UISS-TB.

Background: The STriTuVaD project, funded by Horizon 2020, aims to test through a Phase IIb clinical trial one of the most advanced therapeutic vaccines against tuberculosis. As part of this initiative, we have developed a strategy for generating in silico patients consistent with target population characteristics, which can then be used in combination with in vivo data on an augmented clinical trial.

Results: One of the most challenging tasks for using virtual patients is developing a methodology to reproduce biological diversity of the target population, ie, providing an appropriate strategy for generating libraries of digital patients.

Credibility of In Silico Trial Technologies-A Theoretical Framing.

Different research communities have developed various approaches to assess the credibility of predictive models. Each approach usually works well for a specific type of model, and under some epistemic conditions that are normally satisfied within that specific research domain. Some regulatory agencies recently started to consider evidences of safety and efficacy on new medical products obtained using computer modelling and simulation (which is referred to as In Silico Trials); this has raised the attention in the computational medicine research community on the regulatory science aspects of this emerging discipline.