Quantitative 19F MRI and CT tracking of the microencapsulated stem cells in a rabbit peripheral arterial disease model
Journal of Cardiovascular Magnetic Resonance volume 16, Article number: P61 (2014)
Nearly 12% of Americans suffer from peripheral arterial disease (PAD) and many are not eligible for conventional treatment. Transplanting stem cells (SC) in microcapsules impregnated with X-ray/MR-visible contrast agents (XMRCaps) offers a novel means for PAD therapy to avoid immunorejection and enable tracking using non-invasive imaging modalities. Here we explore quantitative serial cell tracking of XMRCaps using conventional c-arm CT and 19F-MRI containing either human or rabbit SCs (XenoSC or alloSC, respectively) in a non-immunosuppressed rabbit PAD model.
XMRCaps were produced using a modified alginate-poly-L-lysine-alginate microencapsulation method impregnating 12% v/v perfluorooctyl bromine (PFOB) and XenoSC or AlloSC. In vitro validations were performed in an agarose phantom consisting of four layers of 50, 100, and 200 XMRCaps. C-arm CT images (dynaCT, Siemens Artis Zee) were acquired and reconstructed at 0.46 mm isotropic voxel size. 19F 3T MRI was acquired with a 4-channel Tx/Rx 19F coil using a 3D TrueFISP sequence (Siemens Tim Trio, 4.1 ms TR; 2.0 ms TE; 70° FA; 1.3 mm isotropic voxel size; 32 averages). Reference 1H MRI was acquired with the system body or body matrix coil using a 3D gradient echo sequence. In vivo c-arm CT and MRI studies were performed at same day, one and two weeks after an intramuscular injection of 3 ml of XMRCaps in the hindlimb (n = 10) using identical imaging parameters as the in vitro studies (voxel size 1.5 × 1.5 × 2 mm). To test the repeatability of 19F MRI, the imaging sets were acquired twice on the same day in one rabbit with the coil repositioned in between. Reference markers with known PFOB concentrations were placed within the imaging field at the same depth of the injections relative to the coil to enable field inhomogeneity correction. Segmentation of the injection sites in the c-arm CTs and 19F MRIs was performed with the Otsu thresholding algorithm. Concentration was then determined by averaging the integrated 19F signal intensity over the segmented volume after normalization to standards.
CT and MRI XMRCap volumes were highly concordant in vitro (y = 0.8x+3.0, R2 = 0.95) (Figure 1a). 19F MRI repeatability studies showed that the volume and concentration measurement errors were <3% and <6%, respectively. For the AlloSC rabbits, in vivo XMRCap injection volume and concentration decreased 0.2 ± 24% and 7.4 ± 17% respectively each week, compared to the XenoSC rabbits volume increased 1.2 ± 11% and concentration decreased 6.6 ± 17% each week (Figure 1b and 1c).
MRI provides accurate assessment of XMRCap volumes, which were slightly larger than CT due to partial volume effects with the larger MRI voxel size. In vivo XMRCaps injection site volumes could be assessed on MRI and CT. However, only MRI was able to quantify the XMRCaps 19F concentration. Result shows that XMRCaps serial alternations with XenoSC and AlloSC are not significantly different, which demonstrates that XMRCaps prevent the immunorejection of the mismatched SCs.
Siemens AG, NIH R33-HL089029, and the Maryland Stem Cell Research Foundation (2008-MDSCRFII-0399/2011-MDSCRFII-0043).
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Wang, G., Fu, Y., Shea, S. et al. Quantitative 19F MRI and CT tracking of the microencapsulated stem cells in a rabbit peripheral arterial disease model. J Cardiovasc Magn Reson 16 (Suppl 1), P61 (2014). https://doi.org/10.1186/1532-429X-16-S1-P61