Emilia Sue Olson MD, PhD, Presenter: Nothing to Disclose

Christopher Devin Malone MD, Abstract Co-Author: Nothing to Disclose

Inanc Ortac, Abstract Co-Author: Founder, DevaCell Inc

Sadik Esener, Abstract Co-Author: Nothing to Disclose

Robert Frederick Mattrey MD, Abstract Co-Author: Nothing to Disclose

Purpose: Acute renal injury (ARI) is a leading cause of morbidity in ICUs worldwide. Hydrogen peroxide (H2O2), the most common reactive oxygen species is elevated in inflammatory and other conditions including ARI. CATalase loaded Synthetic Hollow Enzyme Loaded nanoSpheres (catSHELS) are nanoencapsulated molecules that catalyze H2O2 to water and oxygen, producing ultrasound detectable microbubbles. In this study we aimed to determine whether catSHELS can convert the H2O2 in acutely injured kidneys to allow their recognition on contrast specific ultrasound imaging.

ARI was produced in 4 pre-heparinized rats by completely occluding the left renal artery for 1 hour followed by 2 hours of reperfusion. After reperfusion, 10^12 particles of non-catalase containing SHELS were given IV. Thirty minutes later, animals were injected with 10^12 particles of catSHELs IV. Both the ARI and normal kidney were imaged immediately after injection and alternately for 10 minutes at 7MHz using the CPS mode of a Siemens Sequoia 512. In addition to subjective observation, video-intensity was measured of the entire kidney and background subtraction was performed. Urine samples were collected before renal artery occlusion and just prior to catSHELS injection.

Echogenic enhancement was only observed in ARI kidneys when catSHELS were injected IV. Intensity of the injured kidneys post IV injection of control SHELS was 0.1±1.3, and increased to 5.0±0.9 post injection of catSHELS (p=0.001). Intensity of the non injured kidney was similar post injection of either control SHELS (-0.49±1.1) or catSHELS (-0.7 ± 2.6,, p=0.86). The difference between the injured and non injured kidneys post catSHEL injection was significant (p=0.02). Urine H2O2 levels increased from 19±8 µM at baseline to 59±24 µM immediately prior to injection of catSHELs.

catSHELS allowed the recognition of acute renal injury by converting the H2O2 produced by the injury into ultrasound detectable microbubbles. Further efforts will involve dose optimization and ultimately translation to the clinic.

ARI is suspected when other conditions that cause decreased urine output are excluded. With the use of this novel ultrasound molecular imaging technique ARI can be diagnosed at the bedside.

Olson, E, Malone, C, Ortac, I, Esener, S, Mattrey, R, Molecular Imaging for the Diagnosis of Acute Ischemic Renal Injury in Rats by in situ Production of Ultrasound Detectable Microbubbles Using Nanoparticles.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14016393.html