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In-Line X-Ray Phase Tomography of Bone and Biomaterials for Regenerative Medicine

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Advanced High-Resolution Tomography in Regenerative Medicine

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Abstract

The aim of this chapter is to present recent developments in X-ray tomography using in-line phase contrast and their applications to mineralised tissue, whether bone or artificial biomaterials, at micro- and nanoscale. Recently, the main efforts in reconstruction algorithms for in-line X-ray phase contrast imaging have been to push resolution towards the nanoscale and extend the possibilities for quantitative imaging to more general objects. The first is made possible by the use of X-ray optics and the second by the introduction of more advanced priors in the reconstruction. We summarise here these developments and outline recent applications of these techniques, namely, nano-tomography of the ultrastructure of bone and micro-tomography of bone formation in artificial bone grafts as well as in healthy growing mice. While still relatively little used in the field of regenerative medicine, we hope that these examples will stimulate further studies in this field.

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References

  1. Bonse U (2002) Developments in X-ray tomography II. Proc. of SPIE 4503

    Google Scholar 

  2. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25(7):1468–1486

    Article  PubMed  Google Scholar 

  3. Engelke K, Karolczak M, Lutz A, Seibert U, Schaller S, Kalender W (1999) Micro-CT. Technology and application for assessing bone structure. Radiologe 39(3):203–212

    Article  CAS  PubMed  Google Scholar 

  4. Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P (1999) Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res 14(7):1167–1174

    Article  CAS  PubMed  Google Scholar 

  5. Salomé M et al (1999) A synchrotron radiation microtomography system for the analysis of trabecular bone samples. Med Phys 26(10):2194

    Article  PubMed  Google Scholar 

  6. Nuzzo S, Peyrin F, Cloetens P, Baruchel J, Boivin G (2002) Quantification of the degree of mineralization of bone in three dimensions using synchrotron radiation microtomography. Med Phys 29:2672–2681

    Article  PubMed  Google Scholar 

  7. Langer M, Prisby R, Peter Z, Guignandon A, Lafage-Proust M-H, Peyrin F (2011) Simultaneous 3D imaging of bone and vessel microstructure in a rat model. IEEE Trans Nucl Sci 58(1):139–145. PART 1

    Article  CAS  Google Scholar 

  8. Prisby R et al (2011) Intermittent PTH 1-84 is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone forming sites. J Bone Miner Res 26(11):2583–2596

    Article  CAS  PubMed  Google Scholar 

  9. Momose A, Takeda T, Itai Y, Hirano K (1996) Phase–contrast X–ray computed tomography for observing biological soft tissues. Nat Med 2(4):473–475

    Article  CAS  PubMed  Google Scholar 

  10. Zanette I et al (2013) Holotomography versus X-ray grating interferometry: a comparative study. Appl Phys Lett 103:244105

    Article  CAS  Google Scholar 

  11. Lang S et al (2014) Experimental comparison of grating- and propagation-based hard X-ray phase tomography of soft tissue. J Appl Phys 116(15):154903

    Article  CAS  Google Scholar 

  12. Varga P, Weber L, Hesse B, Langer M (2016) Synchrotron X-ray phase nanotomography for bone tissue characterization. In: X-ray and neutron techniques for nanomaterials characterization. Springer Berlin Heidelberg, Berlin\Heidelberg, pp 1–42

    Google Scholar 

  13. Langer M, Boistel R, Pagot E, Cloetens P, Peyrin F (2010) X-ray in-line phase microtomography for biomedical applications. In: Méndez-Vilas A, Díaz J (eds) Microscopy: science, technology, applications and education, vol 1., no. 4. Formatex Research Center, Badajoz, pp 391–402

    Google Scholar 

  14. Hagen CK et al (2015) High contrast microstructural visualization of natural acellular matrices by means of phase-based x-ray tomography. Sci Rep 5:18156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bravin A, Coan P, Suortti P (2013) X-ray phase-contrast imaging: from pre-clinical applications towards clinics. Phys Med Biol 58(1):R1–R35

    Article  PubMed  Google Scholar 

  16. Snigirev A, Snigireva I, Kohn V, Kuznetsov S, Schelokov I (1995) On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation. Rev Sci Instrum 66(12):5486

    Article  CAS  Google Scholar 

  17. Cloetens P et al (1999) Holotomography: quantitative phase tomography with micrometer resolution using hard synchrotron radiation x rays. Appl Phys Lett 75(19):2912

    Article  CAS  Google Scholar 

  18. Langer M, Pacureanu A, Suhonen H, Grimal Q, Cloetens P, Peyrin F (2012) X-ray phase nanotomography resolves the 3D human bone ultrastructure. PLoS One 7(8):e35691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Varga P et al (2013) Investigation of the 3D orientation of mineralized collagen fibrils in human lamellar bone using synchrotron X-ray phase nano-tomography. Acta Biomater 9:8118–8127

    Article  CAS  PubMed  Google Scholar 

  20. Hesse B et al (2014) Canalicular network morphology is the major determinant of the spatial distribution of mass density in human bone tissue – evidence by means of synchrotron radiation phase-contrast nano-CT. J Bone Miner Res 30(2):346–356

    Article  CAS  Google Scholar 

  21. Peyrin F, Dong P, Pacureanu A, Langer M (2014) Micro- and Nano-CT for the study of bone ultrastructure. Curr Rev Osteoporos 12:346–356

    Google Scholar 

  22. Hesse B et al (2014) Accessing osteocyte lacunar geometrical properties in human jaw bone on the submicron length scale using synchrotron radiation μCT. J Microsc 255(3):158–168

    Article  PubMed  Google Scholar 

  23. Langer M, Peyrin F (2016) 3D X-ray ultra-microscopy of bone tissue. Osteoporos Int 27(2):441–455

    Article  CAS  PubMed  Google Scholar 

  24. Giuliani A et al (2013) Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: biological and clinical implications. Stem Cells Transl. Med. 2(4):316–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bortel EL et al (2017) Combining coherent hard X-ray tomographies with phase retrieval to generate three-dimensional models of forming bone. Front Mater 4:39

    Article  Google Scholar 

  26. Weber L, Langer M, Tavella S, Ruggiu A, Peyrin F (2016) Quantitative evaluation of regularized phase retrieval algorithms on bone scaffolds seeded with bone cells. Phys Med Biol 61(9):215–231

    Article  CAS  Google Scholar 

  27. Cloetens P et al (1997) Observation of microstructure and damage in materials by phase sensitive radiography and tomography. J Appl Phys 81(9):5878

    Article  CAS  Google Scholar 

  28. Mokso R, Cloetens P, Maire E, Ludwig W, Buffière J-Y (2007) Nanoscale zoom tomography with hard x rays using Kirkpatrick-Baez optics. Appl Phys Lett 90(14):144104

    Article  CAS  Google Scholar 

  29. Cloetens P, Barrett R, Baruchel J, Guigay J-P, Schlenker M (1996) Phase objects in synchrotron radiation hard x-ray imaging. J Phys D Appl Phys 29(1):133–146

    Article  CAS  Google Scholar 

  30. Langer M et al (2014) Priors for X-ray in-line phase tomography of heterogeneous objects. Philos Trans A Math Phys Eng Sci 372(2010):20130129

    Article  PubMed  CAS  Google Scholar 

  31. Davidoiu V, Sixou B, Langer M, Peyrin F (2013) In-line phase tomography using nonlinear phase retrieval. Ann Univ Bucharest Math Ser 4(LXII):115–122

    Google Scholar 

  32. Sixou B, Davidoiu V, Langer M, Peyrin F (2013) Absorption and phase retrieval with Tikhonov and joint sparsity regularizations. Inverse Probl Imaging 7(1):267–282

    Article  Google Scholar 

  33. Davidoiu V, Sixou B, Langer M, Peyrin F (2014) Non-linear phase tomography based on Fréchet derivative. Adv Comput Tomogr 3(4):39–50

    Article  Google Scholar 

  34. Ruhlandt A, Krenkel M, Bartels M, Salditt T (2014) Three-dimensional phase retrieval in propagation-based phase-contrast imaging. Phys Rev A 89(3):33847

    Article  CAS  Google Scholar 

  35. Kostenko A, Batenburg KJ, Suhonen H, Offerman SE, van Vliet LJ (2013) Phase retrieval in in-line x-ray phase contrast imaging based on total variation minimization. Opt Express 21(1):710–723

    Article  PubMed  Google Scholar 

  36. Langer M, Cloetens P, Peyrin F (2009) Fourier-wavelet regularization of phase retrieval in x-ray in-line phase tomography. J Opt Soc Am A Opt Image Sci Vis 26(8):1876–1881

    Article  CAS  PubMed  Google Scholar 

  37. Hehn L et al (2018) Nonlinear statistical iterative reconstruction for propagation-based phase-contrast tomography. APL Bioeng 2(1):16105

    Article  Google Scholar 

  38. Rositi H et al (2014) Computer vision tools to optimize reconstruction parameters in x-ray in-line phase tomography. Phys Med Biol 59(24):7767–7775

    Article  CAS  PubMed  Google Scholar 

  39. Langer M, Cloetens P, Pacureanu A, Peyrin F (2012) X-ray in-line phase tomography of multimaterial objects. Opt Lett 37(11):2151

    Article  PubMed  Google Scholar 

  40. Langer M, Cloetens P, Guigay J-P, Peyrin F (2008) Quantitative comparison of direct phase retrieval algorithms in in-line phase tomography. Med Phys 35(10):4556–4566

    Article  PubMed  Google Scholar 

  41. Paganin D, Mayo SC, Gureyev TE, Miller PR, Wilkins SW (2002) Simultaneous phase and amplitude extraction from a single defocused image of a homogeneous object. J Microsc 206(1):33–40

    Article  CAS  PubMed  Google Scholar 

  42. Langer M, Cloetens P, Peyrin F (2010) Regularization of phase retrieval with phase-attenuation duality prior for 3-D holotomography. IEEE Trans Image Process 19(9):2428–2436

    Article  PubMed  Google Scholar 

  43. Marinescu M et al (2013) Synchrotron radiation X-ray phase micro-computed tomography as a new method to detect Iron oxide nanoparticles in the brain. Mol Imaging Biol 15(5):552–559

    Article  CAS  PubMed  Google Scholar 

  44. Frachon T et al (2015) Dose fractionation in synchrotron radiation x-ray phase micro-tomography. Phys Med Biol 60(19):7543–7566

    Article  CAS  PubMed  Google Scholar 

  45. Weber L et al (2018) Registration of phase-contrast images in propagation-based X-ray phase tomography. J Microsc 269(1):36–47

    Article  CAS  PubMed  Google Scholar 

  46. Moosmann J, Hofmann R, Bronnikov A, Baumbach T (2010) Nonlinear phase retrieval from single-distance radiograph. Opt Express 18:25771–25785

    Article  PubMed  Google Scholar 

  47. Davidoiu V, Sixou B, Langer M, Peyrin F (2013) Nonlinear approaches for the single-distance phase retrieval problem involving regularizations with sparsity constraints. Appl Opt 52(17):3977–3986

    Article  PubMed  Google Scholar 

  48. Pacureanu A, Langer M, Boller E, Tafforeau P, Peyrin F (2012) Nanoscale imaging of the bone cell network with synchrotron X-ray tomography: optimization of acquisition setup. Med Phys 39(4):2229

    Article  PubMed  Google Scholar 

  49. Kingsmill VJ, Boyde A (1998) Mineralisation density of human mandibular bone: quantitative backscattered electron image analysis. J Anat 192(Pt 2):245–256

    Article  PubMed  PubMed Central  Google Scholar 

  50. Giraud-Guille M-M, Besseau L, Martin R (2003) Liquid crystalline assemblies of collagen in bone and in vitro systems. J Biomech 36(10):1571–1579

    Article  PubMed  Google Scholar 

  51. Fratzl P, Weinkamer R (2007) Nature’s hierarchical materials. Prog Mater Sci 52(8):1263–1334

    Article  CAS  Google Scholar 

  52. Schneider P, Meier M, Wepf R, Müller R (2010) Towards quantitative 3D imaging of the osteocyte lacuno-canalicular network. Bone 47(5):848–858

    Article  PubMed  Google Scholar 

  53. Currey JD, Shahar R (2013) Cavities in the compact bone in tetrapods and fish and their effect on mechanical properties. J Struct Biol 183(2):107–122

    Article  PubMed  Google Scholar 

  54. Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 26(2):229–238

    Article  CAS  PubMed  Google Scholar 

  55. Qing H et al (2012) Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res 27(5):1018–1029

    Article  CAS  PubMed  Google Scholar 

  56. Group M, Hero S, Burr DB (1996) In vivo measurement of human tibial strains during vigorous activity. Bone 18(5):405–410

    Article  Google Scholar 

  57. You L, Cowin SC, Schaffler MB, Weinbaum S (2001) A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J Biomech 34(11):1375–1386

    Article  CAS  PubMed  Google Scholar 

  58. Varga P et al (2015) Strains experienced by osteocytes in situ as predicted by case specific finite element analysis. Biomech Model Mechanobiol 14(2):267–282

    Article  PubMed  Google Scholar 

  59. Anderson EJ, Knothe Tate ML (2008) Idealization of pericellular fluid space geometry and dimension results in a profound underprediction of nano-microscale stresses imparted by fluid drag on osteocytes. J Biomech 41(8):1736–1746

    Article  PubMed  Google Scholar 

  60. McNamara LM, Majeska RJ, Weinbaum S, Friedrich V, Schaffler MB (2009) Attachment of osteocyte cell processes to the bone matrix. Anat Rec (Hoboken) 292(3):355–363

    Article  CAS  Google Scholar 

  61. Verbruggen SW, Vaughan TJ, McNamara LM (2012) Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes. J R Soc Interface 9(75):2735–2744

    Article  PubMed  PubMed Central  Google Scholar 

  62. McCreadie BR, Hollister SJ, Schaffler MB, Goldstein SA (2004) Osteocyte lacuna size and shape in women with and without osteoporotic fracture. J Biomech 37(4):563–572

    Article  PubMed  Google Scholar 

  63. Bonivtch AR, Bonewald LF, Nicolella DP (2007) Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis. J Biomech 40(10):2199–2206

    Article  PubMed  PubMed Central  Google Scholar 

  64. Deligianni DD, Apostolopoulos CA (2008) Multilevel finite element modeling for the prediction of local cellular deformation in bone. Biomech Model Mechanobiol 7(2):151–159

    Article  CAS  PubMed  Google Scholar 

  65. Schneider P, Ruffoni D, Larsson D, Chiapparini I, Müller R (2012) Image-based finite element models for the investigation of osteocyte mechanotransduction. J Biomech 45(1):S436

    Article  Google Scholar 

  66. Dorozhkin SV (2010) Calcium orthophosphates as bioceramics: state of the art. J Funct Biomater 1(1):22–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Eliaz N, Metoki N (2017) Calcium phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Materials (Basel) 10(4):334

    Article  PubMed Central  CAS  Google Scholar 

  68. Glazer PA, Spencer UM, Alkalay RN, Schwardt J (2001) In vivo evaluation of calcium sulfate as a bone graft substitute for lumbar spinal fusion. Spine J 1(6):395–401

    Article  CAS  PubMed  Google Scholar 

  69. Komlev VS et al (2006) Kinetics of in vivo bone deposition by bone marrow stromal cells into porous calcium phosphate scaffolds: an X-ray computed microtomography study. Tissue Eng 12(12):3449–3458

    Article  CAS  PubMed  Google Scholar 

  70. Cancedda R et al (2007) Bulk and interface investigations of scaffolds and tissue-engineered bones by X-ray microtomography and X-ray microdiffraction. Biomaterials 28(15):2505–2524

    Article  CAS  PubMed  Google Scholar 

  71. Langer M, Liu Y, Tortelli F, Cloetens P, Cancedda R, Peyrin F (2010) Regularized phase tomography enables study of mineralized and unmineralized tissue in porous bone scaffold. J Microsc 238(3):230–239

    Article  CAS  PubMed  Google Scholar 

  72. Sayer M et al (2003) Structure and composition of silicon-stabilized tricalcium phosphate. Biomaterials 24(3):369–382

    Article  CAS  PubMed  Google Scholar 

  73. Reid JW, Pietak A, Sayer M, Dunfield D, Smith TJN (2005) Phase formation and evolution in the silicon substituted tricalcium phosphate/apatite system. Biomaterials 26(16):2887–2897

    Article  CAS  PubMed  Google Scholar 

  74. Miller LM, Little W, Schirmer A, Sheik F, Busa B, Judex S (2007) Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res 22(7):1037–1045

    Article  PubMed  Google Scholar 

  75. Manjubala I et al (2009) Spatial and temporal variations of mechanical properties and mineral content of the external callus during bone healing. Bone 45(2):185–192

    Article  CAS  PubMed  Google Scholar 

  76. Lange C et al (2011) Fetal and postnatal mouse bone tissue contains more calcium than is present in hydroxyapatite. J Struct Biol 176(2):159–167

    Article  CAS  PubMed  Google Scholar 

  77. Preininger B, Checa S, Molnar FL, Fratzl P, Duda GN, Raum K (2011) Spatial-temporal mapping of bone structural and elastic properties in a sheep model following osteotomy. Ultrasound Med Biol 37(3):474–483

    Article  PubMed  Google Scholar 

  78. Sharir A, Stern T, Rot C, Shahar R, Zelzer E (2011) Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development 138(15):3247–3259

    Article  CAS  PubMed  Google Scholar 

  79. Vetter A et al (2011) The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments. J Biomech 44(3):517–523

    Article  CAS  PubMed  Google Scholar 

  80. Rohrbach D, Preininger B, Hesse B, Gerigk H, Perka C, Raum K (2013) The early phases of bone healing can be differentiated in a rat osteotomy model by focused transverse-transmission ultrasound. Ultrasound Med Biol 39(9):1642–1653

    Article  PubMed  Google Scholar 

  81. Bortel EL, Duda GN, Mundlos S, Willie BM, Fratzl P, Zaslansky P (2015) Long bone maturation is driven by pore closing: a quantitative tomography investigation of structural formation in young C57BL/6 mice. Acta Biomater 22:92–102

    Article  PubMed  Google Scholar 

  82. Douissard P-A et al (2012) A versatile indirect detector design for hard X-ray microimaging. J Instrum 7(9):P09016–P09016

    Article  CAS  Google Scholar 

  83. Golub EE (2009) Role of matrix vesicles in biomineralization. Biochim Biophys Acta, Gen Subj 1790(12):1592–1598

    Article  CAS  Google Scholar 

  84. Vanleene M, Rey C, Ho Ba Tho MC (2008) Relationships between density and Young’s modulus with microporosity and physico-chemical properties of Wistar rat cortical bone from growth to senescence. Med Eng Phys 30(8):1049–1056

    Article  CAS  PubMed  Google Scholar 

  85. Bach-Gansmo FL, Irvine SC, Brüel A, Thomsen JS, Birkedal H (2013) Calcified cartilage islands in rat cortical bone. Calcif Tissue Int 92(4):330–338

    Article  CAS  PubMed  Google Scholar 

  86. Shipov A, Zaslansky P, Riesemeier H, Segev G, Atkins A, Shahar R (2013) Unremodeled endochondral bone is a major architectural component of the cortical bone of the rat (Rattus norvegicus). J Struct Biol 183(2):132–140

    Article  CAS  PubMed  Google Scholar 

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Langer, M. (2018). In-Line X-Ray Phase Tomography of Bone and Biomaterials for Regenerative Medicine. In: Giuliani, A., Cedola, A. (eds) Advanced High-Resolution Tomography in Regenerative Medicine. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-030-00368-5_6

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