Application of MRI phase-difference mapping to assessment of vascular concentrations of BMS agent in mice.

Direct quantitation of contrast agent concentration can be performed using dynamic susceptibility contrast MRI. This method is based on phase imaging and administration of paramagnetic agents such as gadolinium-chelates. This technique has only been applied on humans or primates. However, numerous research models have been developed on small animals like mice. For this reason, the aim of this work was the application of this MRI technique, allowing the direct quantitation of the contrast agent concentrations in vivo, in the mouse vascular system at high field. For this purpose, Dy-DOTA has been preferred to Gd-DOTA due to a lower T(2)* effect. Dy-DOTA shifts in Larmor frequency were measured by phase difference mapping, using fast gradient-echo imaging at short echo times. Such an acquisition sequence allowed the limitation of susceptibility artifacts at high magnetic fields and phase wrapping. As demonstrated in a phantom oriented parallel to the static magnetic field, it is possible to measure contrast agent concentrations between 0 and 10 mm with an uncertainty of about 100 microm. Finally, the method was applied on living mice at 4.7 T. After the bolus injection, the evolution of contrast agent concentrations was assessed in brain blood vessels parallel to B(0). Long-term disappearance of contrast agent was monitored at high spatial resolution every 15 s. Alternatively, lower resolved images at 0.72 s time-resolution allowed preliminary assessment of arterial input functions. The feasibility of quantitative bolus-tracking in small rodents opens the way for comprehensive descriptions of flow and over time-dependent biological processes, especially in pathological murine models.