8 While CT is relatively forgiving due to the ability of the tomographic method to discriminate line-of-sight background, planar angiography is much more susceptible

and often necessitates tens of milliliters per injection, with 20 to 50 injections not uncommonly used in many procedures.9 A consequence of this large concentration of iodinated molecules in the contrast agent formulation Inhibitors,research,lifescience,medical is high osmolality, leading to local irritation, burning sensation, and, in extreme cases, membrane rupture and hemolysis at the injection site.10 11 Second, and most surprisingly, there has been very little attention paid to the pharmacokinetics of contrast agents. Indeed, the initial direction of scanners — towards rapid scanning to overcome the very rapid clearance of injected contrast Inhibitors,research,lifescience,medical agents —has had a “self-fulfilling” effect, whereby contrast agents have always been designed to have rapid clearance. This rapid clearance occurs invariably via the renal route, and the high osmolality (and viscosity)

of the agents leads to acute renal toxcity.12 Indeed, as much as 5% to 10% of the general population, and 25% to 40% of the renally susceptible population, suffers from contrast-induced nephropathy (CIN) after a contrast-CT study.13 14 Ironically, it is this susceptible population that most needs the CT study in the first place. Third, the rapid clearance kinetics (t1/2 Inhibitors,research,lifescience,medical ~ 5 minutes) necessitates a bolus injection and careful timing of the scan to correctly trace the bolus at the moment of entry into the anatomy of interest. This can be challenging, particularly for left-heart-based imaging, since the Inhibitors,research,lifescience,medical intravenous bolus undergoes significant dissipation and dispersion in the pulmonary vasculature prior to collection in, and ejection from, the left ventricle. Thus, at most imaging sites, a “bolus tracking” scan is implemented, which continuously scans a sentinel section immediately upstream of the anatomical region of interest, triggering the scan upon arrival of contrast Inhibitors,research,lifescience,medical in the sentinel.15 However, the bolus tracking scan results in continuous

exposure to X-rays and dramatically increases however the total X-ray dose in such procedures. Indeed, in the pediatric population, where sensitivity to X-ray dose is particularly high and scan doses have been progressively reduced, the bolus tracking contribution to the total dose can be as high as 30% to 40%.16 In spite of all these limitations, however, CT imaging has experienced nothing but continuous growth over the last decade and remains the most widespread imaging technique after ultrasound. The shortcomings of conventional contrast agent kinetics have also been turned into powerful strengths by the clever use of NVP-BKM120 chemical structure delayed-phase imaging. Taking advantage of the rapid renal clearance of contrast agents, arteriography has become the main forte of contrast-enhanced CT.