A new paramagnetically shifted imaging probe for MRI

Purpose: To develop and characterize a new paramagnetic contrast agent for molecular imaging by MRI. Methods: A contrast agent was developed for direct MRI detection through the paramagnetically shifted proton magnetic resonances of two chemically equivalent tert-butyl reporter groups within a dysprosium(III) complex. The complex was characterized in phantoms and imaged in physiologically intact mice at 7 Tesla (T) using three-dimensional (3D) gradient echo and spectroscopic imaging (MRSI) sequences to measure spatial distribution and signal frequency. Results: The reporter protons reside ∼6.5 Å from the paramagnetic center, resulting in fast T₁ relaxation (T₁ = 8 ms) and a large paramagnetic frequency shift exceeding 60 ppm. Fast relaxation allowed short scan repetition times with high excitation flip angle, resulting in high sensitivity. The large dipolar shift allowed direct frequency selective excitation and acquisition of the dysprosium(III) complex, independent of the tissue water signal. The biokinetics of the complex were followed in vivo with a temporal resolution of 62 s following a single, low-dose intravenous injection. The lower concentration limit for detection was ∼23 μM. Through MRSI, the temperature dependence of the paramagnetic shift (0.28 ppm.K⁻¹) was exploited to examine tissue temperature variation. Conclusions: These data demonstrate a new MRI agent with the potential for physiological monitoring by MRI. Magn Reson Med 77:1307–1317, 2017.