MRI characterization of agarose gel micro-droplets at acute time-points within the rabbit lumbar muscle

Agarose gel micro-droplets supplemented with provisional matrix proteins have been shown to enhance encapsulated cell survival for cell therapy applications. This study evaluated micro-droplet T1 and T2 relaxation on a 1.5 T clinical MRI scanner to guide the optimization of encapsulated cell delivery to intermediate-sized animals. Preliminary in vitro experiments using encapsulated human blood-derived endothelial progenitor cells (EPCs) documented a negligible impact of EPC encapsulation on agarose micro-droplet T1 and T2 relaxation, even following transient immersion in 2.3 mm Gd-DTPA. Furthermore, Gd-DTPA immersion did not adversely impact encapsulated cell viability. These results allowed for efficient pre-clinical methodological development using direct injections into the rabbit lumbar region of agarose droplets without cells (n = 6). At time-points to 6 h, in vivo injection sites displayed elevated T2 and T1 (1.8%: ΔT2 = 53 ± 28%, ΔT1 = 50 ± 25%, n = 13; 2.5%: ΔT2 = 41 ± 10%, ΔT1 = 41 ± 26%, n = 11). Rapid imaging sequences displayed high conspicuity at sites of Gd-DTPA-immersed capsule injection, which persisted for less than 4 h. Therefore, basic differences of micro-droplet T1 and T2 when compared to tissue provide a platform for acute tracking of encapsulated cell fate. Transient Gd-DTPA encapsulation accentuates T1 differences.