Monitoring vascular changes in renal fibrosis in mice using multimodal optical and ultrasonic imaging

Chronic kidney disease (CKD) has become one of the major diseases threatening global health, with its increasing incidence and mortality rates. Early identification of chronic kidney disease is crucial for accurate disease staging, timely intervention, and improved prognosis. However, the commonly used clinical diagnostic indicators, such as creatinine, albumin level and glomerular filtration rate, can only identify advanced CKD. Imaging examinations, such as computed tomography and magnetic resonance imaging, have limitations such as high costs and high risk of complications, and are not suitable for large-scale screening of high-risk populations. Renal biopsy is the gold standard for diagnosing renal fibrosis, but it is invasive. Previous studies have shown that capillary rarefaction is an early event of renal fibrosis, occurring earlier than tubular atrophy and interstitial collagen deposition. However, there is a lack of a minimally invasive, low-cost, high-resolution, dynamic and real-time monitoring method for renal microcirculation that is suitable for large-scale screening. There is an urgent need for reliable methods to screen early-stage CKD patients. In this study, we have for the first time combined real-time and wide-field laser speckle imaging (RFLSI), near-infrared II imaging (NIR-II), duplex ultrasound (DUS) and Contrast-Enhanced Ultrasound (CEUS) to monitor vascular changes and evaluate the progression of renal fibrosis. The combination of four imaging methods enabled the early monitoring of CKD progression by monitoring microcirculation. Among them, CEUS can detect changes in the renal microcirculation at the early stage of renal fibrosis, even earlier than the pathological damage of the kidneys. Through visualization and quantification of the progression of renal fibrosis and validation through histopathology, this study utilizes preclinical imaging to supplement clinical imaging of renal fibrosis, providing a more comprehensive method for monitoring microcirculation, which is helpful for guiding clinical decisions and providing insights into disease progression.