In Vivo MRI Tracking of Degradable Polyurethane Hydrogel Degradation In Situ Using a Manganese Porphyrin Contrast Agent.

Abstract

A noninvasive method to track implanted biomaterials is desirable for real-time monitoring of material interactions with host tissues and assessment of efficacy and safety. To explore quantitative in vivo tracking of polyurethane implants using a manganese porphyrin (MnP) contrast agent containing a covalent binding site for pairing to polymers. Prospective, longitudinal. Rodent model of dorsal subcutaneous implants (10 female Sprague Dawley rats). A 3-T; two-dimensional (2D) T1-weighted spin-echo (SE), T2-weighted turbo SE, three-dimensional (3D) spoiled gradient-echo T1 mapping with variable flip angles. A new MnP-vinyl contrast agent to covalently label polyurethane hydrogels was synthesized and chemically characterized. Stability of binding was assessed in vitro. MRI was performed in vitro on unlabeled hydrogels and hydrogels labeled at different concentrations, and in vivo on rats with unlabeled and labeled hydrogels implanted dorsally. In vivo MRI was performed at 1, 3, 5, and 7 weeks postimplantation. Implants were easily identified on T1-weighted SE, and fluid accumulation from inflammation was distinguished on T2-weighted turbo SE. Implants were segmented on contiguous T1-weighted SPGR slices using a threshold of 1.8 times the background muscle signal intensity; implant volume and mean T1 values were then calculated at each timepoint. Histopathology was performed on implants in the same plane as MRI and compared to imaging results. Unpaired t-tests and one-way analysis of variance (ANOVA) were used for comparisons. A P value <0.05 was considered to be statistically significant. Hydrogel labeling with MnP resulted in a significant T1 reduction in vitro (T1=517 ± 36 msec vs. 879 ± 147 msec unlabeled). Mean T1 values of labeled implants in rats increased significantly by 23% over time, from 1 to 7 weeks postimplantation (651 ± 49 msec to 801 ± 72 msec), indicating decreasing implant density. Polymer-binding MnP enables in vivo tracking of vinyl-group coupling polymers. 1. Stage 1.