Paired-site surface-referenced 3D photoacoustic–ultrasound microscopy for quantifying age- and photoexposure-associated skin remodeling

Skin aging reflects age- and photoexposure-associated remodeling, yet noninvasive methods rarely provide unified three-dimensional assessment of pigmentary, vascular, and acoustic changes. We developed a surface-referenced photoacoustic–ultrasound framework integrating adaptive functional stratification with multimodal 3D analysis. Seventy-six adults underwent paired imaging of relatively photoprotected volar and photoexposed dorsal forearms. Volar age trends characterized aging-related patterns at the relatively photoprotected site, whereas age-dependent dorsal–volar contrasts characterized additional remodeling associated with greater habitual photoexposure at the dorsal site. The paired analysis revealed increased and deeper melanin, reduced vascular occupancy and branching with greater patchiness, and lower superficial dermal echogenicity. This framework enables coordinated, layer-specific assessment of skin remodeling in vivo.