VIrtual Twins as tools for personalised clinicAL care

Project Information

VITAL

Grant agreement ID: 101136728

DOI

10.3030/101136728

EC signature date 10 November 2023

Start date 1 January 2024

End date 31 December 2028

Funded under

• Health

Total cost

€ 8 743 516,25

EU contribution

€ 8 743 516,25

Coordinated by

UNIVERSITEIT GENT
Belgium

Periodic Reporting for period 1 - VITAL (VIrtual Twins as tools for personalised clinicAL care)

Reporting period: 2024-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

VITAL will deliver a comprehensive and clinically validated multi-scale, multi-organ modelling platform that can represent individual patient data acquired in the clinic or from wearable technology. The platform will create a virtual human twin for individualised and sex-specific optimization of medical (pharmacological) or surgical (interventional) therapy for complex, multifactorial cardiovascular disorders with systemic impact and a high risk of comorbidities, such as systemic hypertension, heart failure (with or without preserved ejection fraction), and hemodynamically complicated atrial septal defects. The platform will incorporate currently missing biophysics based, physiology-underpinned components, such as kidney-related blood pressure control, hormonal actions,vascular region-specific smooth muscle cell functionality, and cardiac and arterial growth and remodelling mechanobiological mechanisms, which advances the state-of-the-art. User-friendly interfaces, co-created with healthcare professionals, will provide access to the technology. VITAL's virtual human twins have the potential to predict disease progression and treatment outcomes over a period of months to years and offer the possibility of delivering optimised and cost-effective patient management strategies, surpassing current standards of clinical care. The VITAL platform will be validated and tested in over 200 patients across 5 clinical studies in France and the UK to optimise the treatment of patients with resistant systemic hypertension, heart failure, or atrial septum defects.

VITAL will also focus on ethical and legal challenges that are associated with human virtual twin technology. We want to understand the expectations and reservations towards digital health technology of medical doctors and caregivers, but also of the patient. The technology will be compliant with and contribute directly to EU's initiatives to develop the virtual human twin ecosystem, such as the Virtual Physiological Human Institute (VPHi; https://www.vph-institute.org/) and the Ecosystem Digital Twins in Health (EDITH) project (https://www.edith-csa.eu). This will further unlock the potential of new digital tools that intelligently combine the power of physics-based multi-scale models, artificial intelligence, and data to provide better healthcare for all.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first year, we mainly worked on achieving scientific-technical goals:

1) Multi-scale multi-organ model development
Our initial goal of developing a mechanistic (physics-based) infrastructure for multiscale modelling of various cardiac and cardiopulmonary diseases has seen substantial progress, including the ability to integrate across 0D, 1D and 3D models. The integration of the autonomic nervous system, blood flow and cardiac & respiratory mechanics and hormonal pathways, and drug modulation using energy-preserving methods (e.g. bond graphs) is now useable via online databases and tools accessed via web-browsers. With user feedback, starting with the upcoming training course in Delft in March 2025, these will be refined and improved, but a great deal has been achieved during the first 12 months of VITAL. The next major goal is to ensure that all VITAL researchers are familiar with the infrastructure and can contribute their models of physiological function to this common platform to help interpret the clinical data becoming available later during the project.

2) Sensing biomarkers for dynamic personalisation of virtual human twins
We defined the requirements for the pulse wave analysis and the wearable system development.The CALAMARI system, our multi-modal wearable system for biosignal acquisition in prospective studies, advanced faster than anticipated and will be available in Q1 of 2025. Close interaction with the clinical partners has been established. Device-related documentation and training are provided to the clinical institutions to ensure timely inclusion of the wearable device in the prospective studies.

3) Virtual human twin and model personalisation
First results have been achieved for most of our objectives on model personalization, e.g. the verification benchmarks of cardiac mechanics modelling software have been set up, ran, and published; Cross-talk of software codes between multiple groups (, i.e. TU Delft, ELEM, University of Auckland, King's College London, EPFL, University of Maastricht) is currently being explored, and communication in focus circles is ongoing. First personalisation pipelines have been set up, and sharing of knowledge and know-how will be undertaken during the upcoming VITAL Training School in March 2025 in Delft. First steps towards the development of virtual in silico populations, both in 0D, 1D, and 3D have been started up.Surrogate modelling strategies are being explored and applied within various aspects of the modelling framework.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

During its first year, the main focus of VITAL was on its scientific-technical objectives, which form the cornerstone of the multi-scale multi-organ models. Results beyond the state-of-the-art, some still in a preliminary phase and requiring further validation, include
- a VITAL-specific ‘Functional Connectivity’ (FC) map within the SPARC environment (open-science initiative dedicated to advancing the understanding of the nervous system in health and disease - https://sparc.science/) as to provide a ‘Google Street Map’ type interface for multiscale modelling;
- a micro-structurally informed and multi-scale cardiac growth and remodelling model, implemented in two different software platforms, and a modular in-house computational framework to model mechano-driven growth and remodelling in hyperelastic living tissues;
- modelling autonomic nervous control of organs with the development and calibration of a sympathetic neuron model;
- a bond graph model for the human vascular system and organ-level vascular models that link down to exchange mechanisms for hormones and other blood solutes at the tissue capillary level, implemented in CellML (open standard model coding language - https://www.cellml.org/);
- bond graph models for the release and targeting of the different hormones;
- kidney model, with development of bond graph models of several solute carrier (SLC) membrane protein transporters for the kidney;
- development and validation of pharmacokinetics/pharmacodynamics (PK/PD) models of several drugs;
- automation of the process of combining CellML modules into a system model, then doing parameter identification to calibrate to clinical data (available on GitHub);
- built the CALAMARI wearable sensor system that will be used in our future clinical studies.