Collagen organization and biomechanics of the arteries and aneurysms of the human brain

Vascular remodelling is an essential process for growth and development in early life, but later manifestations are often pathological with clinical consequences. Such is the case for saccular and fusiform aneurysms, examples in human biology of outward arterial remodelling with the possible consequence of vascular stroke (Stehbens (1972), Ferguson (1989), ISIUA (1998, 2003), Peters et al. (2001), ISAT (2002)). The common form, the saccular brain aneurysm, is a sphere-like expansion from the artery at the region of a major branch, initially appearing as an outward blister from the lumen. In total there are about 20 arterial branches of the human cerebral circulation (of the many millions of vascular branches, cerebral and non-cerebral) that account for all saccular aneurysms (distribution shown in Fig. 1). Specific branches stand out as the more likely sites, and the anterior cerebral circulation accounts for 87% of all lesions. The incidence of occurrence, including the smallest of 2mm size, is known from autopsy (in the range of 0.2 to 15%, depending on the study) (Hassler (1961), Stehbens (1972)). Only a small fraction are of clinical significance, those presenting with a minor bleed (which are operable) or fatal rupture, thus indicating the challenge for medical course of action for a discovered lesion - intracranial surgery and clipping the neck of the lesion, endovascular procedure, or nonintervention with followup medical imaging. Shown in Fig. 2, prior to treatment, is a large posterior circle aneurysm located at the vertebral-basilar junction, with a manifold of arteries at its neck that ruled out clipping. (An endovascular procedure was used with a good outcome.) There are biomechanical challenges for the remodelling collagen fabric of the extracellular matrix (ECM), fibres that provide the structural backbone of the wall, including the requirement of wall integrity, and strength needed to bear the biaxial loading from blood pressure (Canham and Ferguson (1985), Canham et al. (1996), Humphrey and Kyriacou (1996), David and Humphrey (2003)). A measure of the directional organization of the collagen of the aneurysm wall, layer by layer, provides an assessment of how well or poorly structured an aneurysm is to withstand arterial pressure. It also is a measure of how effective the remodelling process has been from the early stages through to a fragile vessel beyond 10mm in size. Regardless of the underlying biological process, influenced possibly by genetic predisposition (Leblanc et al. (1989)), or localized response to hemodynamic influences (Steinman et al. (2003), Oshima and Torii (2004), Oshima et al. (2005)), the biophysical balance of arterial pressure with wall stress drives the remodelling process and initiates the final event of a bleed into the subarachnoid space. The main thrust of our work has been on the saccular aneurysm and the arteries and their branches where lesions form. For comparison we are including structural results on a fusiform aneurysm, a differently formed lesion characterized by an asymmetrical expansion of brain artery; although far less common they are another example of pathological outward remodelling, and may be similar in fine structure (Drake and Peerless (1997)). Collagen fibres of the ECM have the optical property of birefringence, enabling the measurement of two qualities essential to their function, their orientation in three-dimensional space, which defines the direction they can bear load in a tissue, and the strength of birefringence, which correlates with the ultimate tensile strength of its tissue environment. Two attachments to the polarizing microscope enable the measurement of both qualities - the universal stage attachment that reveals the directional alignment in 3D, fibre by fibre, within a tissue section prepared for light microscopy, and the Sénarmont compensator, which enables the measurement of birefringence. We have exploited both instruments in the study of vascular tissue in order to assess strength and tissue anisotropy (Canham et al. (1999), MacDonald et al. (2000)).