Abstract:

Vasa vasorum, or "vessels of the vessels," are essential for supplementing the physiological transport of nutrients from the blood-filled lumen into the arterial wall in areas of the vasculature with high metabolic demands and/or thicker walls.   In cerebral arteries, it is believed the vasa vasorum only develop in pathological situations, such as in regions of atherosclerotic driven wall thickening.  In this context, they  are largely viewed as having a negative influence on cerebral vascular health.  Similarly, the presence of vasa vasorum in intracranial aneurysm (IA) walls has generally been viewed negatively, due to an association with inflammation.  Moreover,  vasa vasorum in IAs have been implicated in continued growth of large and giant aneurysms, after apparently successful endovascular treatment – ultimately necessitating surgical intervention.

Enlarging aneurysm  must thicken to maintain structural stability and avoid rupture.   In our  study of 82 human brain aneurysm specimens, harvested during open brain surgery, we found the average IA wall thickness to be 370 ± 220 microns, well above the estimated effective oxygen diffusion distance in arteries.   We therefore conjectured vasa vasorum are needed to avoid hypoxia in many IAs.    In this study, we took a multi-modal approach to analyze the vasa vasorum in a single brain aneurysm specimen.    Using scanning immunofluorescent multiphoton imaging (SI-MPM), we identified, for the first time, an extensive vasa vasorum plexus in the IA wall, in contrast to the morphology of vasa vasorum vessels in cerebral arteries. We found a strong correlation between vasa vasorum and increased wall thickness (R.=0.96, P<0.001), and associations with well-defined biaxially oriented collagen fibers, both consistent with a positive role for the vasa vasorum.   A possibly negative influence of the vasa vasorum was related to findings on calcification distribution. Calcification particles were found preferentially located around the  vasa vasorum in the IA wall and large calcifications were found filling  the lumen in sections of three out of four  vessels entering the vasa vasorum network. We then used computational methods to analyze oxygen transport in the same specimen, employing a micro-CT model of the specimen and  high-resolution multi-photon microscopy segmentations of the vasa vasorum network.  The results of this study support the crucial role of vasa vasorum in preventing  hypoxia  in the outer aneurysm wall. 

Contrary to the prevailing view of vasa vasorum as solely adverse, these collective findings highlight an additional protective remodeling role of the vasa vasorum in IA.    These micro-vessels warrant further investigation as there remain many unanswered questions regarding their influence on aneurysm wall pathophysiology and their potential as a biomarker for aneurysm wall stability.

Biography

I am an endowed professor of engineering at the University of Pittsburgh and Research Director of the Bio Tissue and Complex Fluid Laboratory where my team is immersed in investigations of pathologies and healing of soft tissues. We use a variety of tools that range across theoretical, computational and experimental frameworks to pioneer work on the biomechanics of soft tissues with a particular emphasis on cerebral aneurysms, arteries, bladder. Much of our work addresses the relationship between structure (e.g. architecture of the extracellular matrix) and mechanical function (e.g. elasticity, strength) in health and disease.   We explore the capacity for even diseased tissue to regenerate and how this capacity is tied to the patient lifestyle and medical health.

To accomplish these goals, my team has developed new mechanical testing and bioimaging methodologies as our needs have arisen during the process of scientific exploration.  These efforts have led to advances in our understanding of the role of collagen fibers, elastin, calcification and vascular cells in the biomechanical function of organs including arteries, cerebral aneurysms, bladder and tissue engineered blood vessels.   For example, using our custom uniaxial MPM system, we were able to study, for the first time, progressive changes to collagen and elastin architecture during loading in tissue samples without staining, fixation or destructive preparations. Using our approach, we proved a long standing conjecture about the role of collagen and elastin in the stress stretch curve of arteries. We built on this prior work to develp a similarly MPM compatible biaxial testing system. This approach has since been used to great advantage for other tissues.   

Students registered for the seminar are expected to attend in-person.

Teams ID and Passcode:

Meeting ID: 211 123 896 292 8

Passcode: Uh9qs2pf