Ascending thoracic aortic aneurysms characterization in pediatric patients and experimental murine models

The National Heart, Lung, and Blood Institute awarded Purdue University $100,228 under the Cardiovascular Diseases Research program (CFDA 93.837) on January 15, 2027, to characterize ascending thoracic aortic aneurysms in pediatric patients and experimental murine models.

The recipient will use volumetric gated (4D) ultrasound to visualize aneurysm enlargement over time in both adult and pediatric murine models, then apply histological staining and scanning electron microscopy to examine structural changes to the aortic wall. The project will compare human and mouse vessels by performing similar histology and scanning electron microscopy techniques on human samples from an aortic disease biospecimen bank. Physiological information gathered from imaging will be implemented into a computational model of ascending thoracic aortic aneurysms. The work addresses the need for murine models that specifically target the thoracic aorta as a proper comparison to human pediatric aortic disease, since previous murine models have primarily focused on the abdominal aorta and many used adult mice.

Performance period runs from January 15, 2027 through July 17, 2028, with work performed in West Lafayette, Indiana. This is a Project Grant, a form of assistance funding.

Abstract

An aortic aneurysm is a weakening and enlargement of the wall of the aorta that can lead to rupture. Due to the high mortality rates of ruptured aneurysms, screening is often performed on high-risk patients to identify aneurysms in need of surgical repair to prevent rupture. Understanding aneurysmal rupture risk in children is more challenging due to difficulty distinguishing between natural growth with age and pathological expansion. Preemptive surgical intervention to repair an aneurysm is associated with intra- and post-operative challenges. Surgical repair is further complicated in pediatric populations due to continued healthy growth after the procedure. Currently, there are no alternatives to surgery for repairing an expanding aortic aneurysm. The most common location for an aneurysm in pediatric populations is in the ascending thoracic portion of the aorta. However, previous murine models of aortic aneurysm have primarily focused on the abdominal aorta, and many of these murine models utilize adult mice. A need exists to develop and utilize murine models that specifically target the thoracic aorta and that can serve as a proper comparison to human pediatric aortic disease. To contribute to better understanding of aneurysm progression, we plan to use volumetric gated (4D) ultrasound to visualize the enlargement of aneurysms over time in both adult and pediatric murine models. We will then utilize histological staining and scanning electron microscopy (SEM) to understand structural changes to the aortic wall on a more detailed level than can be achieved with in vivo imaging. We will then compare human and mouse vessels by applying similar histology and SEM techniques to human samples from an aortic disease biospecimen bank. Physiological information gathered from imaging will be implemented into a computational model of ascending thoracic aortic aneurysm utilizing an inverse finite element approach to identify intrinsic properties of the vessel wall. Utilizing murine models, multiple imaging modalities, and computational modeling will allow US to develop a better understanding of the pathophysiological conditions surrounding aortic aneurysm progression. Increased understanding of aneurysm development in a pediatric mouse model can lead to more informed decision making about which patients require surgical repair, allowing for more effective intervention.