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

Multiphoton imaging revealed that collagen fiber recruitment distribution in human ACAs becomes narrower with aging and its peak shifts towards lower stretch values, indicating earlier collagen fiber engagement with age.

• Multiphoton imaging of adventitial collagen was performed on human ACAs from n=20 subjects, ages 28-92 years.
• Collagen fiber recruitment for each subject was characterized using a Gamma probability density function (PDF).
• The assumption was that collagen fibers contribute to load bearing only after full straightening.
• The narrowing of the recruitment distribution and peak shift toward lower stretch values together indicate that collagen fibers are recruited earlier (at lower stretches) in older arteries.

Age-dependent collagen fiber recruitment parameters, expressed as continuous functions of age and incorporated into a two-fiber family constitutive model, successfully captured age-related arterial stiffening in human ACAs.

• The mechanical responses of human ACAs from n=49 subjects were characterized using the model.
• Age-related stiffening was reflected by increased initial slopes in the stress-stretch response of older ACAs.
• The Gamma PDF parameters were expressed as continuous functions of age and embedded into the two-fiber family constitutive model.
• The model was validated against data from a previous study of human ACAs spanning a wide age range.

Collagen increasingly dominates load bearing with age in human ACAs, particularly at physiological pressures, as evidenced by a significant increase in circumferential stiffness.

• The increase in circumferential stiffness with age was statistically significant (p < 0.05).
• The model revealed that collagen's contribution to load bearing grows with age, especially at physiological pressure levels.
• This finding provides mechanistic insight into the microstructural origins of cerebral arterial stiffening.
• The shift in load-bearing dominance from elastin to collagen is driven by earlier engagement of collagen fibers in older arteries.

Cerebral arterial stiffening with aging is mechanistically linked to microstructural changes in adventitial collagen fiber recruitment behavior.

• The study population spanned ages 28-92 years, providing a broad range of aging-related microstructural and mechanical data.
• Adventitial collagen was directly imaged using multiphoton microscopy, providing tissue-specific structural data.
• The constitutive modeling framework generalizes the relationship between collagen microstructure and macroscale arterial mechanics.
• The authors propose that these mechanisms may contribute to age-related neurodegenerative progression through cerebrovascular stiffening.

The study introduces a generalizable modeling approach in which imaging-informed microstructural changes are embedded into a constitutive framework as continuous functions of age.

• Gamma PDF parameters describing collagen fiber recruitment were expressed as continuous functions of age, allowing predictions at any age within the studied range.
• The framework couples multiphoton imaging data directly with mechanical constitutive modeling.
• This approach is described as 'generalizable for modeling arterial mechanics informed by tissue-specific microstructure.'
• The two-fiber family model structure accommodates separate fiber families with distinct orientation and recruitment characteristics.