Roughly 10% of the world’s population has chronic kidney disease (CKD). In its advanced stages, CKD greatly increases the risk of hospitalization and death. Although kidney transplantation has revolutionized the care of advanced CKD, clinicians have limited ways of assessing donor kidney quality. Thus, optimal donor kidney–recipient matching cannot be performed, meaning that some patients receive damaged kidneys that function poorly. Fibrosis is a form of chronic damage often present in donor kidneys, and it is an important predictor of future renal function. Currently, no safe, easy-to-perform technique exists that accurately quantifies renal fibrosis. We describe a potentially novel photoacoustic (PA) imaging technique that directly images collagen, the principal component of fibrotic tissue. PA imaging noninvasively quantifies whole kidney fibrotic burden in mice, and cortical fibrosis in pig and human kidneys, with outstanding accuracy and speed. Remarkably, 3-dimensional PA imaging exhibited sufficiently high resolution to capture intrarenal variations in collagen content. We further show that PA imaging can be performed in a setting that mimics human kidney transplantation, suggesting the potential for rapid clinical translation. Taken together, our data suggest that PA collagen imaging is a major advance in fibrosis quantification that could have widespread preclinical and clinical impact.

A class of cancer therapeutic drugs targeting blood vessels, known as vascular disrupting agents (VDAs), induces intertumoral hemorrhage.¹ The drugs are activated at the location of the tumor to disrupt endothelial and/or intravascular cells (e.g., red blood cells), which results in hemoglobin leakage into the surrounding tissues.^{1 – 3} The outcome is vessel disruption followed by tumor cell death and extensive hemorrhagic necrosis within hours of treatment delivery.^4,5

In this work we demonstrate the potential of using nanobubbles (NBs) as radiation therapy enhancers for maximizing tumoral cell death. Photoacoustic (PA) imaging can be used to probe the mechanism of action of this treatment due to its ability to examine the oxygenation of tumors. In vivo experiments were performed in mice bearing prostate cancer tumors and the NB therapies were compared with conventional microbubble (MB) treatments combined with radiation. Our preliminary results show that NB combined with a single dose of 8 Gy radiation induce 40% tumor cell death compared to 20% observed with MB treatments. PA imaging suggest that NBs have an extravascular effect.