A structure-motivated constitutive model of human cerebral arteries with age-dependent collagen fiber engagement

The mechanical properties of cerebral arteries are essential for maintaining normal brain function. Aging promotes arterial stiffening, which accelerates cerebral remodeling and contributes to cognitive impairment. As arterial mechanical behavior is closely related to microstructure, characterizing age-related structural alterations is crucial for elucidating the mechanisms driving neurodegenerative progression. In this study, we developed a structurally motivated constitutive model that incorporates age-dependent changes in adventitial collagen to investigate the mechanical behavior of human anterior cerebral arteries (ACAs). Multiphoton imaging of adventitial collagen was performed on human ACAs (n = 20, ages 28-92 years). Collagen fiber recruitment for each subject was characterized using a Gamma probability density function (PDF), under the assumption that collagen fibers contribute to load bearing only after full straightening. With aging, the recruitment distribution became narrower with its peak shifts towards lower stretch values, indicating earlier collagen fiber engagement. The age-dependent recruitment behavior was then incorporated into a two-fiber family constitutive model by expressing the Gamma PDF parameters as continues functions of age. The model was used to characterize the mechanical responses of human ACAs (n = 49) from our previous study and successfully captured age-related arterial stiffening, reflected by increased initial slopes in the stress-stretch response of older ACAs. Furthermore, the model revealed that collagen increasingly dominates load bearing with age, particularly at physiological pressures, as evidenced by a significant increase in circumferential stiffness (p < 0.05). These findings provide mechanistic insights into the microstructural origins of cerebral arterial stiffening and its potential role in age-related neurodegenerative progression. STATEMENT OF SIGNIFICANCE: Cerebral arterial stiffening with aging increases the risk of cognitive decline and neurodegenerative disease, yet the coupled structural-mechanical mechanisms driving this process remain poorly understood. This study introduces a structurally motivated, age-dependent constitutive model for human anterior cerebral arteries (ACAs) that explicitly incorporates collagen fiber recruitment behavior as a continuous function of age. Collagen fiber recruitment was directly quantified from multiphoton imaging and characterized using a Gamma probability density function. By embedding imaging-informed microstructural changes into a two-fiber family model, this framework provides mechanistic insights into cerebrovascular aging and offers a generalizable approach for modeling arterial mechanics informed by tissue-specific microstructure.