NIR-II photoacoustic/Raman multimodal imaging for early detection of arteriovenous fistula fibrosis

Autologous arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, excessive extracellular matrix (ECM) deposition leading to progressive fibrosis causes AVF dysfunction. Effective methods for accurate visualization and semi-quantitation evaluation of fibrosis progression, particularly at early stages, are still lacking. Herein, we developed a CREKA (Cys-Arg-Glu-Lys-Ala) peptide-functionalized near-infrared-II (NIR-II) photoacoustic (PA)/Raman multimodal probe, PBBT@CREKA nanoparticles (NPs), targeting fibrin–fibronectin complexes overexpressed in the AVF fibrotic microenvironment. By integrating the deep tissue penetration and minimal imaging artifacts of NIR-II PA imaging with the high spatial resolution and strong background resistance of Raman imaging, this platform enables complementary and precise assessment of AVF fibrosis. In the Sprague-Dawley rat AVF models, PBBT@CREKA NPs achieved non-invasive NIR-II PA imaging detection of early fibrosis at depths of 4–10 mm. Simultaneously, Raman imaging provided high-resolution delineation of fibrotic boundaries and detection of microfibrotic foci as small as 0.38 mm × 0.6 mm). Notably, PA/Raman multimodal imaging identified fibrotic lesions prior to morphological changes detected by conventional ultrasound and further revealed that chronic kidney disease aggravates AVF-associated vascular fibrosis, enabling dynamic monitoring of early disease progression. Therefore, this multimodal imaging strategy offers a potential approach for early diagnosis and progression evaluation of fibrosis-driven AVF dysfunction.