A newborn is diagnosed with a heart condition called hypoplastic left heart syndrome in which the left ventricle of the heart is severely underdeveloped, and requires immediate surgery. While there are different surgical options to consider, parents and doctors face a daunting decision of selecting the best procedure, as each poses its own unique benefits and risks. However, today’s advanced technology, like simulation, allow doctors to virtually “clone” the newborn, create an accurate computer model of its heart, run several virtual surgeries, and determine the best type of implantable device in order to determine the outcome of each protocol and select the safest option for actual surgery.
There is a wide spectrum of possible surgical treatments to treat cardiovascular diseases or repair a complex heart defect with the introduction of safer, minimally invasive solutions and implantable devices. In fact, ten years ago, the ability to accurately predict the behavior of an implantable device in the human body was more of a hope and a dream, even for leading companies. Now, safer procedures and technologies have led to the increased use of implantable devices and solutions, but this comes with new challenges.
Medical companies and doctors need to adjust medical devices to the changing lifestyle and lifespan of their patients, who are living longer and have stricter reliability and safety standards of their healthcare solutions. For instance, im plantable devices must not only treat a patient’s condition, it must also perform longer to avoid future complications and surgeries.
In addition, the increasing cost of healthcare, which has increased six times faster than consumer products during the last 30 years, coupled with the tightening and lengthening of the FDA approval process, has hindered the release of new innovative solutions at a pace fast enough to meet demand. As a result, medical companies are leveraging simulation to optimize their product development process to boost the innovation rate while maximizing product reliability to prevent product recalls.
Understanding the Complexities of the Human Body
Before medical companies can design cardiovascular implantable devices, they must first understand the complexities of the human body, specifically the heart, tissue, and blood of the patient. The heart is a very complex pumping engine made of deformable soft tissues driven by a local electrical activity to properly maintain the cardiovascular circulation. Its malfunctions are handled through pacemakers or implantable cardioverter defibrillators (ICDs), which can literally “reset” the heart in case of serious issue. An ICD pulse can be lifesaving, but it is a delicate activity whose reliability is improved by a proper adjustment to the evolving conditions of the patient.
In addition, blood cannot be considered as a simple fluid like air and water, as it is a multiphase combination of cells and platelets flowing together in a deformed artery system under the impulsion of the heart. While the interaction between cells and platelets can usually be overlooked for most medical device designs, its non-Newtonian behavior must be considered for accurate hemodynamics predictions. The non-linear elastic deformations of the artery membrane under the pulsatile blood flow also require proper fluid structure interaction modeling to accurately represent the evolving blood pressure and avoid any unpredicted complication for the patient treated with a given device. Similarly, the introduction of stiff endovascular tools into a soft cardiovascular system can also induce large deformations that might lead to the deterioration of artery walls. (See Figures 1a and b)
Through thermal and fluid simulation, engineers and doctors can accurately model the workings of a patient’s human heart, blood flow, and tissue, as well as the organ’s reaction with surgery and implantable devices. This significantly better understanding and prediction of the human body behavior and the devices interacting with it in the early stage of the product development process not only maximizes the product reliability but boosts the innovation rate and accelerates time to market.
In Silico Design: Evolving Medical Product Development Process
The pioneers and future market leaders are not just doing better than others; they are developing their solution in a different way. All of them have massively adopted engineering simulation to reproduce with necessary accuracy the behavior of the human body and predict the behavior of prototypes first on the computer before starting bench testing (in vitro) and clinical testing (in vivo). This new game changing approach is known as “in silico design.” This new approach translates into the adoption of key best practices, as listed below.
Simulation-Assisted FDA Approval: Aware of potentially negative impact of tightening regulations while willing to guarantee safety of medical devices, the FDA is progressively and conditionally opening the door to computer modeling as the fourth leg of formal testing, together with human, animal, and bench testing. Recent papers by Tina Morrison, PhD, Chief Computational Modeling Advisor for the Office of Device Evaluation at the FDA, illustrate this evolution, as well as workshops aiming to verification and validation of computer- based blood flow. The perspective is to integrate engineering simulation to complement traditional testing to ensure systematic success and accelerate the FDA’s or other regulatory agencies’ approval process.
Taming the Complexity of Human Nature: Computer-based models, especially for complex cardiovascular situations, will never be accepted as part of formal approval or even medical device development if the model reliability is not perfectly demonstrated.
Clinical validations of computer models, especially to predict hemodynamics in various diagnosis and surgical situations, and publications by their peers, are opening the mind of a very conservative clinical world. The systematic clinical validation is the process successfully adopted by leaders to build their credibility for the FDA and hospital communities.
Virtual Human Laboratory: The confidence in the reliability of computer models coupled with extensive validation by clinical collaborations of very active groups (i.e., Virtual Physiological Human, Patient or Physiome in both Europe and North America) is allowing companies to unleash the creativity of their designers and foster brainstorming towards new designs. Intense prototyping is performed in validated virtual human labs, an accurate computerbased representation of the body interacting with the device, so now designers can quickly test, at little cost and no risk for the patient, any concept and reject most of them to identify the few optimal solutions that will be a game-changer in the industry.
In Silico Testing: A large number of computer-based models of patients can be compiled in databases and used for systematic testing of new prototypes. Collecting patient-specific data has been part of standard clinical protocols for a long time, making raw data for in silico testing widely available. Once a new concept has successfully been tested on a database of potentially thousands of virtual patients, confidence is gained that the prototype will sail seamlessly throughout clinical testing and FDA approval.
Entering Both Hospitals and Industrial World
These best practices provide insight into how implantable, cardiovascular devices behave within the human body. They’re spurring new designs that are tested and optimized within the complexities of the human body and are in use today. (See Figure 2)
At the University Hospital of Rennes, France, cardiovascular surgeon Dr. Antoine Lucas recently experienced the value of engineering simulation in a computer-aided surgery planning mode for patients suffering from abdominal aortic aneurysms. Having validated the virtual protocol to predict the deformations of patient specific aorta on more than 20 patients, Dr. Lucas used simulation results as additional surgery planning like stent sizing to ensure patients’ quick and complete recovery.
Lucas reported, “I don’t understand why simulation is used so much in automotive and aeronautic applications and so little in the medical world, where we directly impact a patient’s life. As surgeons, we are spending years to acquire enough know-how and experience to learn how to react quickly when the patient is lying on the operating table; but simulation is giving us the luxury to examine the situation when we still have plenty of time to think through more quietly. I trust that simulation will be used increasingly in the clinical world in the near future.”
In another practice, simulation allows doctors to better predict whether an aortic aneurysm will or will not rupture for a specific patient—ultimately determining if treatment, such as an implantable stent, is required. Two to six percent of the population has at least one aneurysm, usually without knowing it. Ten out of 100,000 will rupture every year with dramatic consequences for the patient. Typical treatment includes aneurysm clipping, which requires surgery or a more minimally invasive treatment, such as coiling and stenting. All these options have the risk of mortality and patients have to determine if they will live with the aneurysm despite the permanent, albeit small, risk of rupture or have the procedure to treat an aneurysm that may never rupture. (See Figure 3)
Professor Vincent Costalat, MD, PhD, and Dr. Mathieu Sanchez in Montpellier, France, have combined transient biomedical imaging with hemodynamic fluid structure interaction in patient specific aneurysm. They are able to specifically simulate the proper calibration of artery wall material properties adjusted to the patient and observe how the transient aneurysm deformations yields to the soft tissue elastic interact. This reveals a clear difference between properties of ruptured and unruptured aneurysms and the combination of in vivo and in silico experiments opens the door to computer-aided diagnoses for rupture of aneurysms.
Understanding how to prevent side effects inherent in the use of implantable devices is also a top concern that can be addressed with simulation. For instance, patients with implantable devices, such as a pacemaker, cannot have MRI scans because of the potentially harmful interaction between the device and the scanner. During an MRI scan, body temperature tends to rise, which is dangerous for tissues. The size and shape of the patient will influence the magnitude of this interaction between the device, scanner, and patient’s temperature. At the Center for Devices and Radiological Health division of Medtronic, both electromagnetic and thermal simulation was utilized to simulate an ICD prototype that was tested within various human bodies experiencing a virtual MRI and did not induce unacceptable local heating.
Accelerating the Pace of Medical Innovations
North American and European medical device companies are rapidly increasing their investment in patientspecific engineering simulation early in the product development cycle to thoroughly understand potential weaknesses of a given implantable device’s design before building a costly prototype, while reducing time to market. This is dramatically accelerates the pace of innovation for cardiovascular therapies, and ultimately improving quality of life.
This article was written by Thierry Marchal, Industry Director, Healthcare, ANSYS, Inc, Canonsburg, PA. For more information, visit http://info.hotims.com/45606-160.