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

Abstract

BackgroundA noninvasive method to track implanted biomaterials is desirable for real‐time monitoring of material interactions with host tissues and assessment of efficacy and safety.PurposeTo explore quantitative in vivo tracking of polyurethane implants using a manganese porphyrin (MnP) contrast agent containing a covalent binding site for pairing to polymers.Study TypeProspective, longitudinal.Animal ModelRodent model of dorsal subcutaneous implants (10 female Sprague Dawley rats).Field Strength/SequenceA 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.AssessmentA 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.Statistical TestsUnpaired t‐tests and one‐way analysis of variance (ANOVA) were used for comparisons. A P value <0.05 was considered to be statistically significant.ResultsHydrogel 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.Data ConclusionPolymer‐binding MnP enables in vivo tracking of vinyl‐group coupling polymers.Evidence Level1.Technical EfficacyStage 1.

Editorial for “In Vivo MRITracking of Polyurethane Hydrogel DegradationIn SituUsing a Manganese Porphyrin Contrast Agent”

“…resorption) over time, demonstrating the potential of the investigated technique for in vivo tracking of degradable polyurethane-based biomaterial with MnPenhanced MRI, with no histopathology-revealed toxicity and less than 2% Mn ion release over 28 days. 8 This work advances our understanding of the efficacy and safety of MnPs as labeling contrast agents for noninvasive tracking of implanted biomaterials in vivo.…”

“…The article by Tawagi et al specifically presented a class of MnPs containing a covalent binding site for pairing to polymers. In vitro and in vivo MRI‐based assessment of the MnP‐labeled hydrogels was performed and compared with unlabeled hydrogels 8 . Tawagi et al showed that covalently labeling hydrogels with MnPs led to a significant reduction in T1 relaxation times in vitro.…”

“…In this issue of JMRI, Tawagi et al have investigated MnPs as T1 contrast agents for quantitative in vivo tracking of degradable polyurethane hydrogels on 3.0 T MRI. 8 The article by Tawagi et al specifically presented a class of MnPs containing a covalent binding site for pairing to polymers. In vitro and in vivo MRI-based assessment of the MnPlabeled hydrogels was performed and compared with unlabeled hydrogels.…”

“…In vitro and in vivo MRI-based assessment of the MnPlabeled hydrogels was performed and compared with unlabeled hydrogels. 8 Tawagi et al showed that covalently labeling hydrogels with MnPs led to a significant reduction in T1 relaxation times in vitro. Moreover, this study showed that MnP-labeled implants were clearly distinguishable from surrounding tissues and fluids in vivo and that T1 values of the labeled implants significantly increased from 1 to 7 weeks following dorsal implantation in a rat model.…”