Towards a system level modeling approach to improve mechanical ventilation
This pandemic COVID-19 outbreak has called for all possible acceleration in medical innovation to improve immunity and to stay prepared to treat the adversity on health grounds. Besides the in vivo and in vitro approaches, the in-silico ways would complement this mission. Such advanced adoption of computational modeling offers many advantages starting with patient safety going on to personalized treatments, bringing down the invasive routes of drug administration to make it more painless. The focused work on Novel Drug Delivery Systems (NDDS), a 505 (b) (2), or a Paragraph 4 filing would benefit by better optimization when the right set of simulations are devised to pave the way on.
Ethical concerns on animal testing have also been spinning off lately to grab more attention into the in-silico adoption. Digitalization and simulation put up to the right use, there’s more data generated and that would come from more candidates analyzed by a larger sample on the Design of Experiments (DOE).
The outputs derived from simulations can be better quality inputs for the PBPK/PD models to work with. So, the modeling studies actually can be ranging from a 3D component level to a system level. System-level simulations or the Reduced Order Models (ROM) derived from a detailed 3D model simulation can present quicker ways of analyzing even biological units to for necessary responses or stimuli in a virtual environment.
Even the fields as niche as tissue culture, genetics can benefit very much from computational modeling with a focus to virtually study the sensitivity of the cells to the imposed bio-environment. What if scenarios on the impeller speed, fill level and the positioning of the scaffold, etc.., can be virtually studied to find the right answers before going to be physical. Forensic science as well seeks to use simulations to discover the root cause of the victim’s damage, such as explaining the angle of attack of a bullet based on the sort of wound it plunged in the body.
As mentioned, while 3D simulations are always there to cater to the finest details needed, developing system-level models is also equally important to be quick at attending to treatments for patients requiring personalized therapies. As of today, even surgeons with a very limited mathematical background can leverage computational modeling successfully to plan and execute critical, life-sustaining surgeries proving to be a bliss to the enrolled patients.
In the case of a life-sustaining mechanical ventilator, the focus is to use patient-specific operational conditions for the pressure applied based on the flow rate of the ventilation. This is to avoid any Ventilator Induced Lung Injury (VILI) which can be either acute possibility or unless for Severe Acute Respiratory Syndrome (SARS) such as COVID-19. The below-shown representation is a system-level network built with Ansys Twin builder by mechanical & electrical elements to represent the reaction of an artificial lung connected to an input waveform from a mechanical ventilator.
The model input is a pressure wave supplied to the lung (cylinder with piston) through the trachea (pipe). A flow sensor is used as an en-route to measure the flow rate. Mechanical spring and damping are used to represent resistance and compliance. We can see the conversion from cmH2o to Pascal & Liter’s to m3 in the above expressions to match the medical unit system for the mechanical Spring and damping coefficients.
The below representation is the simulation result as the lung volume and flow rate as a reaction to the fed pressure waveform
In addition to the system modeling, a 3D simulation is performed using the Ansys CFD tools on a lung airway model. A real-time breathing cycle is used as an input to such simulation.
An initial pursuit has been set up to conceive a simulator which can offer an easily accessible platform to test and monitor a pressure signal and other parameters during artificial ventilation. Besides the deployment for regular medical care, this simulator is intended for academic learning and training as well. The outlook is about simulating a 3D Computational Fluid Dynamics (CFD) model and building a Reduced Order Model (ROM) of the breathing cycle in Ansys Fluent. Such ROM shall then be integrated with Twin Builder to develop a holistic response system.