Volumetric photoacoustic imaging of elastin and age-related remodeling using near-infrared probe ElaNIR

Elastin supports tissue elasticity and structural stability, but its regeneration is minimal in adulthood. Monitoring elastin remodeling is therefore important for understanding aging and related cardiovascular disease. However, fluorescence imaging lacks penetration for deep-tissue visualization, while histological methods are invasive, endpoint-based, and limited in volumetric assessment. Here, we demonstrate 3D multispectral photoacoustic computed tomography (PACT) for volumetric assessment of ElaNIR, a near-infrared elastin-targeted probe. Multispectral unmixing separates ElaNIR signals from endogenous hemoglobin, enabling depth-resolved visualization of probe distribution within anatomical context. Young mice showed strong, uniform ElaNIR signals in elastin-rich tissues, including skin and ear, whereas aged mice showed reduced and discontinuous signals. In contrast, aged mice exhibit increased ElaNIR signals in clearance-related organs, including kidneys, liver, and bladder, suggesting altered probe retention and biodistribution with aging. These results establish 3D multispectral PACT as a volumetric imaging framework that integrates elastin-associated probe retention with organ-level biodistribution for interpreting age-related changes.