Understanding pediatric pulmonary hypertension Creating new imaging and modeling tools to improve diagnosis and management

Image caption: Multi-scale modeling framework of the cardiopulmonary system. Credit: Figueroa et al.

by Kim Roth

Pulmonary hypertension (PH), a lung disorder that causes high blood pressure in the pulmonary arteries, affects an estimated 15 million to 50 million individuals worldwide. Its progressive nature, impact on quality of life, and life-threatening long-term consequences make it an important focus of basic scientific and translational research.

“Pulmonary hypertension is a relatively rare disease, but the incidence is likely underestimated, since definitive diagnosis currently requires an invasive heart catheterization” says C. Alberto Figueroa, the Edward B. Diethrich M.D. Associate Professor of Biomedical Engineering and Vascular Surgery.

In addition, non-invasive diagnostic tests, and those used to assess severity, can be highly subjective. Existing treatments mainly target symptoms rather than the underlying cause, which can also be hard to identify. Over time, PH can lead to heart failure; in many cases, patients require a heart or lung transplant.

Particularly in children, diagnosing and treating PH poses unique challenges. Their smaller size and faster heart rate make imaging more difficult than in adult patients.

With U-M colleague Adam Dorfman, MD, associate professor of pediatric cardiology, and colleagues at Michigan State University and Nationwide Children’s Hospital, Figueroa is developing a comprehensive multiscale model of the cardiopulmonary system in pediatric PH.

Using data from MRI and heart catheterization studies in 25 patients – 20 with PH and five cardiac transplant controls – computational models will integrate clinical information, including vessel stiffness and geometry and heart structure and function. The result will be high-resolution simulations of both blood flow dynamics and tissue mechanics of the entire cardiopulmonary system.

Over the four-year study, the team will investigate well-known mechanistic factors at work in PH.

“We know that PH is characterized by smooth muscle hypertrophy, endothelial dysfunction and deposition of collagen and elastin, which result in biomechanical alterations in the system, such as increased resistance and stiffness. While we know that these mechanistic parameters play a critical role, we don’t yet have a full understanding of how they interact and potentially lead to decompensated right ventricular failure,” says Figueroa. “One of our goals is to identify a series of mechanistic markers – rather than the existing subjective assessment tools – to use for patient stratification.”

The work builds upon Figueroa’s previous research. Prior to joining the U-M faculty in 2014, he developed new algorithms to perform simulations of fluid-structure interactions in cardiovascular models constructed from image data. Thanks to the algorithms, simulation of blood flow and artery dynamics in full-scale models became possible.

The exceptional computational resources within the College of Engineering and the world-class clinical expertise in PH management, in both adult and pediatric populations, make U-M the right place to carry out this latest study, Figueroa says.

Ultimately, the goal is to create new imaging and computational modeling tools to improve diagnosis and management of PH on a patient-specific basis.

“If our effort is successful, we might reduce or eliminate the need for risky and invasive catheterization procedures,” -Alberto Figueroa

“If our effort is successful, we might reduce or eliminate the need for risky and invasive catheterization procedures,” says Figueroa. The findings also will be applicable to systemic hypertension, which affects some 36 percent of Americans.

Longer term, Figueroa and Dorfman hope to create a patient-specific computational framework to test the efficacy of new drugs.

“Once we understand the mechanisms better,” says Dorfman, “we can work toward more effective ways of treating pediatric PH. Because, really, at the end of the day, we’re trying to help kids be kids.”

The effort is funded by a $2.4 million U01 grant from the National Institutes of Health, U01HL135842: Image-Based Multi-Scale Modeling Framework of the Cardiopulmonary System: Longitudinal Calibration and Assessment of Therapies in Pediatric Pulmonary Hypertension.

Taking the Guesswork out of Surgical Planning How BME professor Alberto Figueroa’s patient-specific blood flow simulations help clinicians find the ideal surgical path

 
by Aimee Balfe

Alberto Figueroa’s BME lab has achieved an important goal – using computer-generated blood flow simulations to plan complex cardiovascular procedures.

“We’re now using virtual surgical planning in the clinical realm, not as a retrospective theoretical exercise,” says Figueroa.

Using patients’ medical and imaging data, Figueroa can create a model of their unique vasculature and blood flow, then use it to guide surgeons and cardiologists through specific operations and procedures. One type of procedure involves placing grafts in the inferior vena cava to help alleviate complications from pulmonary arteriovenous malformations (PAVMs).

“We’re now using VIRTUAL SURGICAL PLANNING in the clinical realm, NOT AS A RETROSPECTIVE THEORETICAL EXERCISE.” Alberto Figueroa

PAVMs – abnormal connections between a patient’s veins and arteries – are a common complication of a procedure performed early in the lives of children born with only a single functioning ventricle. Called the Fontan procedure, the operation rewires patients’ pulmonary circulation so that the venous return bypasses the heart and is connected directly to the pulmonary arteries for transport to the lungs.

While these surgeries can be lifesavers, the long-term consequences depend heavily on how evenly blood flow is distributed between a patient’s lungs. Patients with ideal hemodynamics do well; those with less-than-perfect flow patterns suffer a sting of life-threatening complications, such as low blood oxygen and elevated cardiac output.

Figueroa’s technique can help those with complications by better balancing flow to the lungs.

Simulation & Outcome: A Perfect Match

“What we bring to the table in operations like this is, instead of going in blind, we can simulate multiple different ways of doing the procedure to see if there is an optimal one.”

Figueroa makes use of detailed anatomical data such as CT scans, Doppler data on velocity in various vessels, invasive catheterization data that shows pressures at multiple locations, and perfusion data from nuclear medicine tests. His lab creates hemodynamic models of each patient that match these data points precisely. They then simulate multiple different ways of placing a stent graft using U-M's high performance Flux computing cluster, provided by Advanced Research Computing, to identify the best outcome.

“During these procedures, the surgeons use angiograms to illuminate the blood flow,” says Figueroa. “This has shown that the results match what our computer simulation predicted.” (See image.)

“The clinicians were amazed, but we told them we were just solving Newton’s law.”  Alberto Figueroa

 

Before (left) and after (right) images from an angiogram (top) and a surgical simulation (bottom). Note the tight correlation between the simulations and angiograms as well as the significantly more even distribution of hepatic venous flow between the two lungs after a simulation-guided procedure. Credit: Kevin Lau, Alberto Figueroa.

Better Primary Surgeries

In addition to corrective surgeries, these simulation techniques can also allow surgeons to optimize initial procedures like the Fontan so that complications may never happen at all.

Of the tens of thousands of patients undergoing Fontan operations each year, he says, roughly half experience major complications after 10 years. That’s because it’s almost impossible for surgeons to know exactly how to perform the procedure on patients with vessels of various sizes, shapes, and flows.

By accounting for these differences, Figueroa hopes his simulations will show surgeons where in the vasculature to make the surgical connections so that blood flow is ideally balanced between the lungs in each patient. He plans to work with U-M colleagues on patient-specific Fontan planning.

And because his simulations add a layer of insight to any procedure where cardiologists and surgeons find that doing things the same way works in some patients and not others, Figueroa hopes they’ll soon become a ubiquitous precision planning tool, much like imaging is today.

Additional Applications

As promising as it is, surgical planning is only the tip of the iceberg for Figueroa. His lab also works to further develop its simulation software and to use it to understand disease progression, always with an eye toward devising better treatments.

In the software arena, his lab is working on enhancements that will account for dynamic changes in blood flow caused by anything from a change in posture to anesthesia.

One of the lab’s clinical fellows is studying how blood vessels remodel in response to the grafts used in thoracic aneurysm repair. Another is modeling aortic dissection, aiming to discover precisely how the flap that shears from the vessel wall moves, deforms the aorta, and affects blood flow. This understanding is a first step toward designing a device specifically for this condition.

His lab also hosts BME students who are developing tools to better understand blood flow in the brain, clot-development in veins, and the progression of hypertension, including which types of vessels sustain various degrees of damage over time. Figueroa has recently submitted a collaborative grant to explore the progression of pulmonary hypertension, as well.

The breadth and clinical relevance of his work are in many ways why Figueroa came to U-M from King’s College, London, two years ago. Named the Edward B. Diethrich M.D. Research Professor of Biomedical Engineering and Vascular Surgery, Figueroa, a PhD, was drawn by his 50/50 appointment in BME and vascular surgery at an institution where medicine and engineering are deeply integrated.

It’s because of this connection that rapid-response surgical planning is made possible, he says. It’s also given him ready access to talented students from the medical and engineering schools – and to usually hard-to-reach study participants, like aortic dissection patients, to gain critical insight into this and other life-threatening conditions.