Delta relaxation enhanced MR: improving activation-specificity of molecular probes through R1 dispersion imaging

MR molecular imaging enables high-resolution, in vivo study of molecular processes frequently utilizing gadolinium-based probes that specifically bind to a particular biological molecule or tissue. While some MR probes are inactive when unbound and produce enhancement only after binding, the majority are less specific and cause enhancement in either state. Accumulation processes are then required to increase probe concentration in regions of the target molecule/tissue. Herein, a method is described for creating specificity for traditionally nonspecific probes. This method utilizes MR field-cycling methods to produce MRI contrast related to the dependence of R(1) upon magnetic field. It is shown that the partial derivative of R(1) with respect to magnetic field strength, R(1)', can be used as an unambiguous measure of probe binding. T(1)-weighted images and R(1)' images were produced for samples of albumin and buffer both enhanced with the albumin-binding agent Vasovist. For T(1) images, samples with low concentrations of Vasovist in an albumin solution could not be differentiated from samples with higher concentrations of Vasovist in buffer. Conversely, the R(1)' images showed high specificity to albumin. Albumin samples with a 10-microM concentration of Vasovist were enhanced over buffer samples containing up to 16 times more Vasovist.