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X-ray CT in Phase Contrast Enhancement Geometry of Alginate Microbeads in a Whole-Animal Model

Abstract

Imaging soft biomaterials in vivo is a significant challenge, as most conventional techniques are limited by biomaterial contrast, penetration depth, or spatial resolution. Exogeneous contrast agents used to increase contrast may also alter material properties or exhibit local toxicity. The capability to observe biomaterial constructs in vivo without introducing exogenous contrast would improve preclinical testing and evaluation. Conventional X-ray Computed Tomography allows fast, high-resolution imaging at high penetration depth, but biomaterial contrast is low. Previous studies employing X-ray phase contrast (XPC) and utilizing a synchrotron source provided support for the significant potential of XPC in imaging biomaterials without contrast agents. In this study, XPC tomography was used to image alginate hydrogel microspheres within a small animal omental pouch model using a commercially available X-ray source. Multilayer microbeads could be identified in the XPC images with volumetric and structural information not possible in histological analysis. The number of microbeads present and microbead volume and diameter could be quantified from the images. The results of this study show that XPC tomography can be a useful tool for monitoring of implanted soft biomaterials in small animal models.

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References

  1. 1.

    Appel, A., M. A. Anastasio, and E. M. Brey. Potential for imaging engineered tissues with X-ray phase contrast. Tissue Eng. Part B 17:321–330, 2011.

  2. 2.

    Appel, A. A., M. A. Anastasio, J. C. Larson, and E. M. Brey. Imaging challenges in biomaterials and tissue engineering. Biomaterials 34:6615–6630, 2013.

  3. 3.

    Appel, A. A., V. Ibarra, S. I. Somo, J. C. Larson, A. B. Garson, 3rd, H. Guan, J. P. McQuilling, Z. Zhong, M. A. Anastasio, E. C. Opara, and E. M. Brey. Imaging of hydrogel microsphere structure and foreign body response based on endogenous X-ray phase contrast. Tissue Eng. Part C 22:1038–1048, 2016.

  4. 4.

    Appel, A. A., J. C. Larson, S. Somo, Z. Zhong, P. P. Spicer, F. K. Kasper, A. B. Garson, 3rd, A. M. Zysk, A. G. Mikos, M. A. Anastasio, and E. M. Brey. Imaging of poly(alpha-hydroxy-ester) scaffolds with X-ray phase-contrast microcomputed tomography. Tissue Eng. Part C 18:859–865, 2012.

  5. 5.

    Arifin, D. R., D. A. Kedziorek, Y. Fu, K. W. Chan, M. T. McMahon, C. R. Weiss, D. L. Kraitchman, and J. W. Bulte. Microencapsulated cell tracking. NMR Biomed. 26:850–859, 2013.

  6. 6.

    Arifin, D. R., C. M. Long, A. A. Gilad, C. Alric, S. Roux, O. Tillement, T. W. Link, A. Arepally, and J. W. Bulte. Trimodal gadolinium-gold microcapsules containing pancreatic islet cells restore normoglycemia in diabetic mice and can be tracked by using us, ct, and positive-contrast mr imaging. Radiology 260:790–798, 2011.

  7. 7.

    Chen, Y., and M. A. Anastasio. Properties of a joint reconstruction method for edge-illumination X-ray phase-contrast tomography. Sens. Imaging 19:7, 2018.

  8. 8.

    Cormode, D. P., W. J. Mulder, and Z. A. Fayad. Science to practice: versatile method to track transplanted encapsulated islet cells with multiple imaging modalities. Radiology 258:1–2, 2011.

  9. 9.

    Khanna, O., J. C. Larson, M. L. Moya, E. C. Opara, and E. M. Brey. Generation of alginate microspheres for biomedical applications. J. Vis. Exp. 66:e3388, 2012.

  10. 10.

    Khanna, O., M. L. Moya, E. C. Opara, and E. M. Brey. Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1. J. Biomed. Mater. Res. Part A 95:632–640, 2010.

  11. 11.

    Kim, J., D. R. Arifin, N. Muja, T. Kim, A. A. Gilad, H. Kim, A. Arepally, T. Hyeon, and J. W. Bulte. Multifunctional capsule-in-capsules for immunoprotection and trimodal imaging. Angew. Chem. Int. Ed. Engl. 50:2317–2321, 2011.

  12. 12.

    Kollmer, M., A. A. Appel, S. I. Somo, and E. M. Brey. Long-term function of alginate-encapsulated islets. Tissue Eng. Part B 22:34–46, 2015.

  13. 13.

    Mollenhauer, J., M. E. Aurich, Z. Zhong, C. Muehleman, A. A. Cole, M. Hasnah, O. Oltulu, K. E. Kuettner, A. Margulis, and L. D. Chapman. Diffraction-enhanced X-ray imaging of articular cartilage. Osteoarthr. Cartil. 10:163–171, 2002.

  14. 14.

    Moya, M. L., S. Lucas, M. Francis-Sedlak, X. Liu, M. R. Garfinkel, J. J. Huang, M. H. Cheng, E. C. Opara, and E. M. Brey. Sustained delivery of fgf-1 increases vascular density in comparison to bolus administration. Microvasc. Res. 78:142–147, 2009.

  15. 15.

    Moya, M. L., M. Morley, O. Khanna, E. C. Opara, and E. M. Brey. Stability of alginate microbead properties in vitro. J. Mater. Sci. Mater. Med. 23:903–912, 2012.

  16. 16.

    Shokrollahi, H. Contrast agents for MRI. Mater. Sci. Eng. C 33:4485–4497, 2013.

  17. 17.

    Somo, S. Synthesis and Evaluation of Stablized Alginate Microbeads, in Biomedical Engineering. Chicago: Illinois Institute of Technology, 2017.

  18. 18.

    Somo, S. I., O. Khanna, and E. M. Brey. Alginate microbeads for cell and protein delivery. Methods Mol. Biol. 1479:217–224, 2017.

  19. 19.

    Somo, S. I., K. Langert, C. Y. Yang, M. K. Vaicik, V. Ibarra, A. A. Appel, B. Akar, M. H. Cheng, and E. M. Brey. Synthesis and evaluation of dual crosslinked alginate microbeads. Acta Biomater. 65:53–65, 2018.

  20. 20.

    Veriter, S., J. Mergen, R. M. Goebbels, N. Aouassar, C. Gregoire, B. Jordan, P. Leveque, B. Gallez, P. Gianello, and D. Dufrane. In vivo selection of biocompatible alginates for islet encapsulation and subcutaneous transplantation. Tissue Eng. Part A 16:1503–1513, 2010.

  21. 21.

    Zhu, N., D. Chapman, D. Cooper, D. J. Schreyer, and X. Chen. X-ray diffraction enhanced imaging as a novel method to visualize low-density scaffolds in soft tissue engineering. Tissue Eng. Part C 17:1071–1080, 2011.

  22. 22.

    Zysk, A. M., A. B. Garson, 3rd, Q. Xu, E. M. Brey, W. Zhou, J. G. Brankov, M. N. Wernick, J. R. Kuszak, and M. A. Anastasio. Nondestructive volumetric imaging of tissue microstructure with benchtop X-ray phase-contrast tomography and critical point drying. Biomed. Opt. Express 3:1924–1932, 2012.

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Acknowledgments

This was work supported, in part, by funding from the National Institutes of Health (Grants 5R01EB020604), the National Science Foundation (CBET-1263994, IIS-1125412) and the Department of Veterans Affairs (5 I01 BX000418-06).

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Correspondence to Jacob Brown.

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Brown, J., Somo, S., Brooks, F. et al. X-ray CT in Phase Contrast Enhancement Geometry of Alginate Microbeads in a Whole-Animal Model. Ann Biomed Eng 48, 1016–1024 (2020). https://doi.org/10.1007/s10439-019-02291-4

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Keywords

  • XPC
  • Tomography
  • Alginate
  • Microbeads