A virtual patient.  That’s what we’re looking for to reduce costs and accelerate the innovation of medical devices and treatments, including those using 3D printing.  And it is these virtual patients that can be a crucial component in helping entrepreneurs and researchers bolster their products for clinical trials. We sat down with five experts who are making computer, or in silico, simulations a reality to benefit patients worldwide.  Here’s a recap of the progress they’ve made and the challenges to come from our 3DHEALS event.

The conventional pathway for developing a medical device can be fraught with expense if problems are found too late in the process.  In silico simulations provide an avenue for researchers and companies to discover effective solutions faster and detect issues earlier.

Already, the United States Food and Drug Administration (FDA) has recognized the increasing utility of computational modeling and recently established guidance on assessing the credibility of in silico evidence for medical device submissions.

Virtual Patients, Not Too Far Away

Simon Sonntag, CEO and Co-Founder of Virtonomy, is streamlining the use of these types of computer simulations using virtual patient cohorts, or simulated versions of patients that mimic a variety of anatomical conditions with the goal of maximal population coverage.  This could be a potentially cost-effective way to test 3D-printed devices before clinical trials and provide evidence for the trials themselves.

Sonntag described how testing a device for transcatheter applications, such as replacing a heart valve, can be challenging due to the variability in vessel tortuosity and diameters between patients.  Virtonomy’s database of computed tomography scans enables them to model a diverse range of vascular geometries for the transfemoral, inferior vena cava, subclavian/jugular vein, and transseptal via the fossa ovalis access routes.

For vessel straightening, the company can simulate the device materials, catheterization process, arterial material, surrounding organs and bones, and calcification. 3D models like these allow users to readily tune anatomical features with their software, testing worse-case scenarios and inclusion-exclusion criteria that can then be used as evidence for regulatory assessments.

Within only a 3-week submission window for a severely ill patient, the company was able to perform in silico fatigue simulations, which provided critical evidence to the German regulatory agency that approved the implantation of the heart valve repair system.

In Silico Simulation Can Help 3D Printed Implants

Companies are also developing software for other parts of the body.  Kelsey Crossman, Business Development Manager for Simq, describes how the company’s software performs biomechanical simulations of maxillary and mandibular patient-specific implants.  Their product, Simq VIT, automates device validation by simulating physiological load conditions and generates FDA-compliant reports as valuable objective evidence of the design process.  The implant can then be 3D printed with greater confidence in point-of-care applications or sent to a manufacturer.

Crossman says their software simulates various chewing conditions, allowing engineers and clinicians to revise their designs based on deformation data before they print.  The company has also developed simulations for virtual patient cohorts and is expanding to thoracic applications.

In Silico Simulation Compliments 3D Printing in Complex Surgical Cases

Also using simulation techniques, Dr. Péter Éltes, Head of the In Silico Biomechanics Laboratory at the National Center for Spinal Disorders in Hungary, recognizes that simply designing custom implants that fit the natural geometry after the surgical removal of structures is not enough.

Dr. Éltes’ recent study uses finite element analysis to determine the stability of lumbopelvic reconstruction after removal of the sacral bone due to a tumor.  Through their in silico analysis, they find that reducing the lumbopelvic distance is needed to increase stability.  Future custom-made 3D-printed implants can now be designed with this added stability technique in mind, showing the potential of computer simulations to inform the engineering of commercial and research 3D-printed medical devices for better clinical outcomes.

Regulatory Landscape Promising but Remains Promising

We have already seen that in silico simulations hold promise in accelerating clinical trials.  Building justification for that potential, Steven Kreuzer, Senior Managing Engineer at Exponent Inc., co-led a team involving the FDA and Dassault Systèmes to retrospectively examine the benefits in silico simulation would have had for an approved mitral transcatheter edge-to-edge repair device to reduce heart valve regurgitation.

Kreuzer describes how they created a tunable virtual patient model for various heart valve anatomies, accounting for differences in thickness, stiffness, and other properties between different valve leaflets.  They then created virtual patient cohorts with a wide distribution of valve properties, looking at the grade reduction in regurgitation among the patients to evaluate the acute device performance.

In Silico Simulation for Pharma Developers, A Different Beast

In silico simulation has applications in drug discovery and development, in addition to medical devices.  Anthony Fejes, CEO and Co-Founder of HTuO Biosciences, is preparing to commercialize the company’s software, which performs physics-based simulations to predict drug behavior. Their software bridges the gap between the high accuracy of quantum mechanics-based simulations and the scalability of molecular modeling software.

In external validation, Fejes showed that the company’s product AtomForge could reduce errors in modeling molecule torsion angles by 82% and out-of-plane errors by 84% for the worst-case scenario, a significant improvement compared to a prior state-of-the-art, the generalized AMBER force field, on the nonsteroidal anti-inflammatory drug mefenamic acid.  The company has also shown lower errors for other drugs that are difficult to simulate compared to OpenFF, another state-of-the-art method.

Perhaps one day, we could combine such drug simulation platforms with 3D bioprinted tissues for in vitro studies of drug candidates, potentially accelerating the process further compared to traditional animal testing.

While in silico simulations have been shown to be a promising avenue for a larger number of use cases, various challenges remain.  For example, Kreuzer notes that work still needs to be done to garner wider acceptance of these technologies for clinical trials.

Sonntag also points out that there could be hurdles if there are differences in the kinds of in silico clinical trial data certain countries will accept, emphasizing the importance of harmonizing regulatory standards internationally.

Additionally, certain artificial intelligence-based simulations may require large amounts of training data, limiting their applicability.

Our speakers show that computational simulations have immense potential to continue growing in their number of use cases, and the 3D printing industry will benefit from the acceleration of the device development and clinical trial process.  To listen in on the full discussion with our speakers, you can watch the recording of our event, and subscribe to join our upcoming events live.

Peter Hsu

Peter Hsu is an editorial intern for 3DHEALS.  He is currently an undergraduate at the University of Illinois Urbana-Champaign and studies bioengineering with a focus on cell and tissue engineering.  He is also minoring in computer science with interests in artificial intelligence and image processing.  Peter conducts research on using computer vision methods to analyze human tissue images and improving the robustness of machine learning workflows.  He is interested in the use of AI to assist tissue engineering and bioprinting research for medical applications.  He is passionate about science communication and leads STEM outreach lessons at schools in the central Illinois area.

Related Links:

Event Recap: Innovation in Melt-Electrowriting (MEW) & 3D Printing

In Silico Simulation for Medtech and Biopharma (Full Recording, On Demand, 2024)

Interview with Zsolt Pásztor: In Silico Simulation and 3D Printing

Interview with Simon Sonntag: CEO, Virtonomy

Virtual Reality Software For Molecular Modeling and Structure-Based Drug Design

3D Printing for Medical Simulation (On Demand)

Design for Medical 3D Printing (On Demand)

Point of Care 3D Printing (On Demand)

Interview with Kelsey Crossman: Simq Simulation

The post Event Recap: In Silico Simulation for Medtech and Biopharma appeared first on 3DHeals.

Want to write a piece for 3DHEALS Expert Corner? Email us: info@3dheals.com

Over the past decade, there has been an exponential increase in the utilization of 3D printing technologies for cardiovascular applications. 3D printing is being utilized in many cardiovascular centers of excellence for surgical planning and simulation, trainee education and patient counseling.

I. Surgical planning and pre-procedural simulation

To attain the best surgical outcomes, cardiac surgeons need to operate efficiently and obtain the best possible surgical result on their first attempt. This requires a keen understanding of complex three-dimensional anatomy, a high level of technical skill, and the ability to make critical decisions in a short amount of time. Each of these factors is enhanced by 3D printing.

Currently, the standard of care requires surgeons to mentally reconstruct complex 3D anatomy from stacks or sweeps of 2-dimensional images; echocardiograms, MRIs or CTs. “3D” volume rendered images go a step further to show spatial relationships, but are limited by the 2D displays on which they are usually shown. On the other hand, 3D-printed models are replicas of the patient’s own unique anatomy that a surgeon can hold, manipulate and obtain a very detailed understanding of complex anatomy. Examples are shown in Figure 1.

When printed in flexible and compliant materials, surgeons can cut, suture and engraft patches, conduits, and essentially perform a simulated surgery before stepping into the operating room. In so doing, surgeons effectively get a “practice swing” before performing the actual surgery. This type of precise pre-surgical planning potentially offers several benefits:

• Reductions in procedure time, which has been linked to improved surgical outcomes.
• Planning for contingencies (Plan A, Plan B, etc) and “bailout” strategies
• Fewer residual lesions and decreased re-intervention rate
• Shorter post-operative hospital stays given the relatively recent growth of cardiac 3D printing to date there have been no long-term studies to date confirming the potential benefits above. However, clinical utilization is growing, and several papers have reported promising applications of the technology (1-8). In addition, early data from the otolaryngology experience is showing reductions in procedure time (9-10).

II. Trainee Education

There is an often quoted idiom in medical education: “See one, Do one, Teach one.” This refers to a model of medical training that has persisted as long as the medical profession itself; an apprenticeship model whereby medical trainees learn from the observation and teachings of more experienced clinicians.

In the method, teaching is both didactic and experiential, essentially learning through experience in live cases. Our greatest surgeons have trained in this method, and over time they have accumulated a high degree of skill after performing large numbers of cases and committing thousands of hours of practice. At the same time, further examination of this model of medical education makes plain some of its drawbacks:

• It is highly dependent on the availability of teaching cases – both the number of cases and a wide variety of complexity required to provide a solid training experience
• Variability of teaching skill and experience of the educator
• Learning via practice on actual patients. This last point is particularly noteworthy; it is an inescapable reality of the current medical system, which has overall worked well for generations, though not particularly comforting to patients or their families. 3D printing technologies provide solutions that enhance trainee education to overcome some of the limitations above5. 3D printed models that represent the spectrum of complex cardiovascular abnormalities can be made for trainees to perform difficult procedures, limited only by their access to the technology. This helps transition from solely an apprenticeship model to a “simulator-based” learning model that has already made other industries safer. As an example, consider the airline industry and training with flight simulators. With 3D printed models we can now provide the next generation of trainees the “1000 hours” (or more) of practice they need performing complex procedures. This new approach augments current education methods and standardizes the ways in which future heart surgeons are trained, hopefully producing surgeons who are better prepared to operate on live patients.

III. Patient and Family Counseling

One of the bedrocks of the practice of medicine is the cultivation and practice of empathy. Empathy is what allows us to put ourselves in our patient’s shoes and imagine their medical experience from their perspectives. It is what helps us connect with the families we serve and ultimately work as a team to tackle medical problems. To that end I invite you to engage in this thought exercise: imagine being a patient, or the parent of a young child, who is learning a complex diagnosis for the first time. Then imagine having to make difficult and complicated decisions regarding this diagnosis, which may involve high-risk surgery. These are the types of situations our patients and families face on a daily basis, and the process of patient and family counseling is fraught with challenges. Some of these challenges have to do with the complexity of the disease, which may interfere with the patient’s ability to make informed decisions about medical or surgical options. For cardiac cases, 3D printed models allow the patient to hold a replica of their own heart while his/her physician goes over their diagnosis, treatment options, and the planned procedure. Just as it was for experienced surgeons and trainees, 3D models offer the patient a higher level of understanding of their own anatomy, hopefully enhancing the informed consent process, and helping patients and families make better decisions (11-12).

IV. Future Directions & Transformative Partnerships

While cardiac applications of 3D printing have advanced far in the past decade, the next few years promise to be even more exciting. 3D printing will help push the envelope of personalized medicine, opening up possibilities that were simply unavailable in the past without this technology. One example is cardiac bioprinting, which will allow the engraftment of patient-matched 3D printed cardiac structures (valves, vessels, myocardium, etc) (13-14). Other advanced applications include 3D printing for functional 3D modeling, which allows physicians to integrate physiology into 3D models and predict the outcomes of surgeries. Finally, it is very likely that 3D printing using biocompatible materials will be applied to develop the next generation of cardiac implants and devices. 3D printed implants are now routinely used in non- cardiac specialties (ex: orthopedics, craniofacial, dentistry), and the technology is ready for adoption for cardiac applications. These advanced implants will overcome the limitations of currently available products and further improve surgical outcomes.

To achieve the next generation of breakthroughs, new transformative partnerships will be essential. The rapid evolution and complexity of this technology makes collaboration essential for the stakeholder sectors; academic, medical, and commercial. These transformative and synergistic partnerships will undoubtedly elevate patient care and result in improved medical outcomes in the near future.

Disclosure: Dr. Anwar is a Consultant at Printerprezz, a medical innovation company utilizing additive manufacturing, nanotechnologies, and surgical expertise to design and manufacture next-generation medical devices based in Fremont, CA.

References:

1. Anwar, S et al. 3D Printing in Complex Congenital Heart Disease: Across a Spectrum of Age, Pathology, and Imaging Techniques. JACC: CV Imaging. 2016. http://doi.org/10.1016/j.jcmg.2016.03.013

2. Farooqi, et al. Application of Virtual3D Models for Simultaneous Visualization of Intracardiac Anatomic Relationships in Double Outlet Right Ventricle. Pediatr Cardiol. 2015 Aug 9;37(1):90–8.

3. Farooqi, et al. 3D Printing to Guide Ventricular Assist Device Placement in Adults With Congenital Heart Disease and Heart Failure. JACC: Heart Failure. 2016, 4(4), 301–311.

4. Ryan JR , et al. A novel approach to neonatal management of tetralogy of Fallot, with pulmonary atresia, and multiple aortopulmonary collaterals. JACC: CV Imaging. 2015 Jan 1;8(1):103–4.

5. Costello, et al. Incorporating 3D Printing into a Simulation‐based Congenital Heart Disease and Critical Care Training Curriculum for Resident Physicians. Congenital Heart Disease. 2015 Mar 1;10(2):185

6. Anwar, S., Singh, G. K., Miller, J., Sharma, M., Manning, P., Billadello, J. J., et al. (2018). 3D Printing is a Transformative Technology in Congenital Heart Disease. JACC: Basic to Translational Science, 3(2), 294–312. http://doi.org/10.1016/j.jacbts.2017.10.003

7. Tack, P., Victor, J., Gemmel, P., & Annemans, L. (2016). 3D-printing techniques in a medical setting: a systematic literature review. BioMedical Engineering OnLine, 1–21. http://doi.org/10.1186/s12938-016-0236-4

8. Byrne, N., Velasco Forte, M., Tandon, A., Valverde, I., & Hussain, T. (2016). A systematic review of image segmentation methodology, used in the additive manufacture of patient-specific 3D printed models of the cardiovascular system. JRSM Cardiovascular Disease, 5, 2048004016645467.http://doi.org/10.1177/2048004016645467

9. Zweifel DF, Simon C, Hoarau R, Pasche P, Broome M Are Virtual Planning and Guided Surgery for Head and Neck Reconstruction Economically Viable? Journal of Oral and Maxillofacial Surgery 2015

10. Rogers-Vizena, C. R., Sporn, S. F., Daniels, K. M., Padwa, B. L., & Weinstock, P. Cost-Benefit Analysis of Three-Dimensional Craniofacial Models for Midfacial Distraction: A Pilot Study. The Cleft Palate-Craniofacial Journal. 2017.

11. Hu A, et al. Three-dimensional Educational Computer Model of the Larynx: Voicing a New Direction. Arch Otolaryngol Head Neck Surg. American Medical Association; 2009.

12. Bernhard, J. et al. Personalized 3D printed model of kidney and tumor anatomy: a useful tool for patient education. World Journal of Urology, 2016.

13. Bin Duan. State-of-the-Art Review of 3D Bioprinting for Cardiovascular Tissue Engineering. Annals of Biomedical Engineering. Springer US; 2016 Aug 18;1–15

14. Noor N, Shapira A, Edri R, Gal I, Wertheim L, Dvir T. 3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts. Advanced Science. John Wiley & Sons, Ltd; 2019 Apr 15;135:1900344.

About the Author

Dr. Shafkat Anwar is a pediatric cardiologist with a specialty in non-invasive cardiac imaging, including echocardiography and cardiac magnetic resonance imaging (MRI). 

He is the Pediatric Cardiology Director of Cardiac MRI, as well as Co-Founder and Co-Director of the UCSF Center for Advanced 3D+ Technologies (CA3D+). He is a founding member and the inaugural Chair of the Advanced 3D+ Visualization Special Interest Group in the Society for Cardiovascular Magnetic Resonance. He is a consultant at Printerprezz, a medical start-up in Fremont, CA utilizing additive and other advanced manufacturing technologies to develop the next generation of medical devices.  At Printerprezz Dr. Anwar serves as the Senior Vice President of Medical Innovations. Dr. Anwar completed his internship and residency in Pediatrics at Children’s National Medical Center, as well as a research fellowship at the National Institutes of Health. He completed fellowships in Pediatric Cardiology and Cardiac Imaging at Cleveland Clinic and Children’s Hospital of Philadelphia. Prior to joining UCSF, Dr. Anwar was Cardiology Director of Cardiac MRI at Washington University in St. Louis, St. Louis Children’s Hospital.  At Wash. U. Dr. Anwar co-founded and co-directed the Center for 3D Printing, a multi-disciplinary 3D printing center

Related Articles:

From 3D Printing to VR/AR: Simple Connection?

Interview: Justin Ryan, 500+ Heart Models later…

Interview: Dr. Sujatha Buddhe, Pediatric 3D Printing, Seattle

Interview: Dr. Chen Ching Kit, Pediatric Cardiac 3D Printing, Singapore

Idea to Implementation: Revenue Strategies for 3D Printing for Pre-surgical Planning

The post Cardiac 3D Printing: The Heart of the Matter appeared first on 3DHeals.

Professor Clarençon is an interventional neuroradiologist and Head of the Pitié-Salpêtrière University Hospital Department of Interventional Neuroradiology in Paris. He is a specialist of intracranial aneurysms, brain AVMS and fistulas, as well as spinal vascular malformations, mechanical thrombectomy and percutaneous spine intervention. Pr. Clarençon’s doctoral thesis was on advanced imaging techniques for brain arteriovenous malformations. He will be presenting at the event in Paris on Nov 21st, 2017.
 
 
 
 
Jenny: What inspired you to use 3D printing?
Clarençon: The 3D printing represents for me a leap forward in the management of our patients. 3D printing may also be very useful to teach our residents and fellows. The leitmotiv nowadays for the resident is “Never the first time on a patient”.
Jenny: What is the biggest motivation for your work?
Clarençon: To cure patients of their severe cerebrovascular diseases with a low complication rate.
Jenny: What is the biggest challenge in your work?
Clarençon: To improve the safety of our treatments
Jenny: How do you plan to conquer this challenge?
Clarençon: The use of flow model obtained via the 3D printing technology may be a new way to better plan the strategy of our treatments.
Jenny: What is your vision on the potential impact of your current work to the future of medicine?
Clarençon: I am working mainly on tools to better analyze the angioarchitecture of brain AVMs, and on new paradigms for the treatment of these aggressive vascular lesions. The goal is to reduce the complication of the curative treatment of this disease.
Jenny: What is the biggest change/improvement since last year this time?
Clarençon: In my field, the flow diverter stents for the treatment of an intracranial aneurysm are a paradigm shift. The recent evidence on the effectiveness of mechanical thrombectomy in acute ischemic stroke with large vessel occlusion is also a big change in our specialty.
Jenny: What are you passionate about?
Clarençon: Neurosciences and literature.
Jenny: What is the biggest risk you took in your career?
Clarençon: We take risks every day, because our endovascular techniques are at risk of severe complications, even if they rarely occur.
Jenny: What do you enjoy in your spare time?
Clarençon: I have almost no spare time (…). I enjoy Paris with my wife (art exhibits, theatre plays, opera …).

The post Interview with Professor Frédéric Clarençon: 3D Printing and Interventional Neuroradiology appeared first on 3DHeals.