Breathing New Life into Lung Research with Simulation

Challenge: At the University of California Riverside (UCR), bMECH lab (the BioMechanics Experimental & Computational Health Lab led by Principal Investigator Dr. Mona Eskandari) researchers were faced with the challenge of modeling the human lung, an organ so complex that it requires simulations that capture interactions spanning from microscopic alveoli to whole-organ mechanics. A lack of experimental data poses another hurdle, as lung tissue is intricate and differs between patients. Even existing data that comes from animal studies limits the representation of human lungs.

Solution: The simulation capabilities of SIMULIA Abaqus provided bMECH lab with advanced tools capable of handling the lung’s complex geometries, non-linear materials, and intricate interactions. By integrating experimental data with computational models, SIMULIA Abaqus enabled real-time calibration and validation, bridging the gap between physical testing and predictive simulations for lung disease research.

In the near future, this research could be helpful for mechanical ventilation optimization, where the model can predict how lungs deform under different ventilation strategies, therefore improving outcomes for COPD and COVID-19 patients; and also provide insights into lung disease by adjusting tissue properties, where the model can be used to study how conditions such as emphysema alter lung mechanics at a whole-organ level.

Benefit: The bMECH lab recognized that simulation allowed them to test “what if” scenarios, such as exploring different ventilation strategies or disease conditions, without risking patient harm. This approach provided continuous, multi-scale data, significantly accelerating research timelines and enabling the development of predictive healthcare tools for personalized treatment strategies.

The Challenge: Decoding Lung Complexity

When we think about breathing, it seems simple: inhale, exhale, repeat. However, for those involved in lung research, such as Dr. Arif Badrou at UC Riverside’s BioMechanics Experimental & Computational Health Lab (the bMECH Lab), led by Principal Investigator Dr. Mona Eskandari, it was clear there was much more happening: breathing is an elaborate, coordinated process involving chemical reactions and mechanical movements. The lungs work across multiple scales. Tiny alveoli at the microscopic level interact with airways and tissues at the macro level, creating challenges not only in understanding lung function but in effectively modeling it for research and clinical applications.

“It’s interesting to see how many approaches are being used to fight a chronic lung disease. So first of course we have the medical community, such as pulmonologists who are diagnosing and treating patients directly, and beyond that we have researchers and engineers who are developing new devices, better diagnostic tools and also improved treatments, and methods of prevention. It’s a strong collective effort to fight chronic lung disease. As a researcher, my work involves developing new medical tools, including improved surgical sealants for lung tumor removal and advancing targeted treatment for radiation therapy, as well as the development of biofidelic lung models, to better treat and understand lung mechanics, which hopefully will guide better treatments.”

This complexity has profound implications for studying pulmonary diseases. Conditions like emphysema and chronic bronchitis affect the lungs’ microscopic air sacs to airway tissues. These diseases often overlap and progress unpredictably. Compounding the problem is the difficulty in diagnosing lung issues early; by the time symptoms are noticeable, the damage is often irreversible.

In addition to optimizing mechanical ventilators, this kind of model could also be used to represent alterations in physiological response, such as lung volume reduction or tumor resection (when parts of the lung are removed or severely altered). In the future, it could also be applied to represent drug inhalation and evaluate treatment performance.

For Badrou, Eskandari, and bMECH colleagues at UCR, creating accurate lung models faced significant obstacles. Lung tissue is intricate, and experimentation requires precision. While previous studies used data from animal tests or were limited to single pressure-volume measures of the whole lung, highly limited in any spatial or temporal measures of the lung and how the response varied across the organ, tissue, or microstructural scale.  For years, this lack of data constrained the research field, limiting the ability to create predictive, high-fidelity models.

“Building a model of the human lung is really difficult and for different reasons. The first reason is that the lungs affect different aspects and different levels, micro and macro levels, and simulating and modeling all this interaction can be very difficult, given the numerical capacities. For example, if I have a disease like chronic bronchitis, lung tissue may become stiffer. It will reduce lung function. You need to have an interaction between the micro level, where the tissue is stiffer. And then you need to model the global, whole-organ behavior of the lungs. I would say it is difficult for this reason in particular. And another reason is the validation for whether you are developing a model for a human lung or for any other organs, you need careful validation with real-world data and getting that kind of data is not easy.”

The Breakthrough Solution

With Dr. Eskandari’s invention of a breathing mimicry apparatus enabling unprecedented collection of valuable spatio-temporal experimental data, Dr. Badrou’s work took a pivotal turn, facilitating the bMECH Lab’s creation of the first 3D structural model of the breathing lung in partnership with Dassault Systèmes’ industry-leading simulation platform, SIMULIA. This collaboration united academic expertise with cutting-edge engineering, resulting in a truly groundbreaking approach.

This iterative experimental-computational approach is centered on ventilating human lungs to replicate breathing in a controlled environment. Actual cadaveric human lung specimens, as well as lungs from pigs, rats, and mice, were employed, inflated through the trachea, just as they would function in a living body. By simulating physiological breathing patterns, the apparatus allowed the bMECH Lab to replicate real-world conditions while minimizing confounding variables that could skew the data.

“SIMULIA’s ability to handle non-linear materials, contact and complex geometry is very advanced. When working with biological systems such as the lungs, it is very useful and I would say it helps improve our workflow so we can focus more on the science than coding and software issues.”

This electromechanical device is interfaced with digital image correlation techniques from traditional metallurgical approaches, adapted to capture the rapid and large breathing deformations that characterize the lung’s tissue-level strains. This merged experimental setup is unmatched in its ability to generate continuous, multi-scale experimental data, providing the foundation from which novel computational models may be constructed. By bridging the crucial gap between laboratory experimentation and computational simulation, this project provides the data accuracy needed to ensure models reflect lung mechanics and behavior.

Why Simulation Changed Everything

While the breathing mimicry apparatus provided new data, the role of advanced simulation truly unlocked its potential. SIMULIA enabled bMECH to not only process experimental data but to explore previously untouchable aspects of lung function.

Before integrating simulation, analyzing lung behavior involved weeks spent building and troubleshooting models, a manual process that delayed progress. With SIMULIA, what once took weeks now happens in days. The platform’s ability to handle non-linear materials, complex biological geometries, and intricate tissue interactions allowed Badrou and the team to focus more on advancing research instead of grappling with software constraints.

“Simulation can be used in different ways and is important because I think there is a misconception, like when people talk about simulation and they think about it being something extra, something we don’t need, but I believe simulation offers something invaluable.”

Through simulation, Badrou could safely and effectively test “what if” scenarios. This tool lets him virtually explore how diseases like chronic bronchitis alter lung stiffness or how alternative ventilation methods might help a patient with reduced lung capacity and mitigate ventilator-induced lung injury (VILI). These insights couldn’t be achieved through experimental work alone.

“SIMULIA’s ability to handle non-linear materials, contact and complex geometry is very advanced. And when working with biological systems such as the lung, it is very useful. And I would say it helps improve our workflow and focus more on the science rather than coding and software issues. Because if we do everything from scratch, it will take a lot of time. SIMULIA’s projects help us save a lot of them. What used to take weeks in terms of model development and debugging, we can now achieve in a few days.”

The benefits extend beyond efficiency. Together, the breathing apparatus and simulation pipelines form an iterative feedback loop. Experimental data from the apparatus informs the models, and simulations help refine and optimize experimental designs. This iterative process has propelled Dr. Eskandari’s bMECH lab at UCR into uncharted territory, connecting the dots between physical and computational worlds.

The Living Lung Project

Inspired by the successes of the Living Heart Project, which reshaped cardiac research, bMECH applied these principles to pulmonary health, resulting in an ambitious partnership with Dassault Systèmes known as the Living Lung Project in 2020. 

The project aims to develop a generalized model of the human lung, mapping out mechanical properties and physiological behaviors comprehensively. Combining real tissue data from our experiments with SIMULIA’s simulation tools, we are creating a model capable of capturing the smallest chemical interactions to the full-scale dynamics of respiratory cycles.

“We are trying to create a generalized human lung model. This is not patient-specific. In the future, we want it to be adapted to each patient for something personalized and precision medicine. The human lung model I’m trying to develop in this pipeline is to calibrate material parameters based on the experimental data. We made the connection between the experimental side and the numerical pipeline. And if we have a single generalized human lung model, then we can add the physiological changes caused by lung disease into our model, which is something very complex, because when working with lungs or other organs, there are many difficulties.”

While we are starting with a broader model, the future lies in personalization. Imagine a world where clinicians could fine-tune treatment plans for patients based on personalized simulations of their lungs. This would potentially revolutionize not just how lung diseases are treated but also how to prevent them.

A Vision for the Future

Over the next decade, Badrou sees the potential to expand from a generalized lung model to patient-specific tools. These tools would allow researchers to predict how a patient’s lung disease might progress and assess how specific treatment strategies could improve outcomes.

Badrou’s role in the bMECH lab aims to push beyond reactive medicine and into predictive healthcare. Some of the most exciting possibilities involve detecting at-risk individuals before symptoms appear, enabling prevention strategies that save lives and reduce healthcare costs.

“By joining all of these ongoing efforts like SIMULIA’s projects with advanced numerical simulation and combining with differencing and with a strong collective effort from researchers, clinicians, and also public health initiatives, I really believe we can do something that can really help predict and understand lung disease better.”

Achieving this vision will take continued collaboration. Partnerships like the one fostered with Dassault Systèmes are crucial. Expertise in simulation amplifies the research, transforming what once seemed insurmountable into tangible progress.

Conclusion

Badrou is proud to be at the forefront of pulmonary research. By tackling the intricate challenges of lung modeling head-on,  Dr. Eskandari’s bMECH lab at UCR is paving the way for breakthroughs that could redefine how respiratory diseases are diagnosed and treated. Advanced experimentation and simulation are not just tools; they are integral to the future of personalized, predictive healthcare.

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