Understanding pediatric pulmonary hypertension
Creating new imaging and modeling tools to improve diagnosis and management
Multi-scale modeling framework of the cardiopulmonary system. Credit: Figueroa et al.
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.