Combining Coherent Hard X-Ray Tomographies with Phase Retrieval to Generate Three-Dimensional Models of Forming Bone

Holotomography, a phase sensitive synchrotron-based μCT modality, is a quantitative 3D imaging method. By exploiting partial spatial X-ray coherence, bones can be imaged volumetrically with high resolution coupled with impressive density sensitivity. This tomographic method reveals the main characteristics of the important tissue compartments in forming bones, including the rapidly-changing soft tissue and the partially or fully mineralized bone regions, while revealing subtle density differences in 3D. Here we show typical results observed within the growing femur bone midshafts of healthy mice that are 1, 3, 7, 10 and 14 days old (postpartum). Our results make use of partially-coherent synchrotron radiation employing inline Fresnel-propagation in multiple tomographic datasets obtained in the imaging beamline ID19 of the ESRF. The exquisite detail creates maps of the juxtaposed soft, partially mineralized and highly mineralized bone revealing the environment in which bone cells create and shape the matrix. This high resolution 3D data is a step towards creating realistic computational models that may be used to study the dynamic processes involved in bone tissue formation and adaptation. Such data will enhance our understanding of the important biomechanical interactions directing maturation and shaping of the bone micro- and macro-geometries.

[1]  F. Peyrin,et al.  3D X-ray ultra-microscopy of bone tissue , 2016, Osteoporosis International.

[2]  Georg N Duda,et al.  Long bone maturation is driven by pore closing: A quantitative tomography investigation of structural formation in young C57BL/6 mice. , 2015, Acta Biomaterialia.

[3]  Françoise Peyrin,et al.  Synchrotron X-ray phase nano-tomography-based analysis of the lacunar–canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis , 2014, Biomechanics and Modeling in Mechanobiology.

[4]  F. Pfeiffer,et al.  Ptychographic X-ray nanotomography quantifies mineral distributions in human dentine , 2015, Scientific Reports.

[5]  Georg N Duda,et al.  Skeletal maturity leads to a reduction in the strain magnitudes induced within the bone: a murine tibia study. , 2015, Acta biomaterialia.

[6]  P. Cloetens,et al.  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 , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  Kay Raum,et al.  The early phases of bone healing can be differentiated in a rat osteotomy model by focused transverse-transmission ultrasound. , 2013, Ultrasound in medicine & biology.

[8]  Françoise Peyrin,et al.  Investigation of the three-dimensional orientation of mineralized collagen fibrils in human lamellar bone using synchrotron X-ray phase nano-tomography. , 2013, Acta biomaterialia.

[9]  Georg N Duda,et al.  Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl/6 mice coincides with a reduction in deformation to load. , 2013, Bone.

[10]  H. Riesemeier,et al.  Unremodeled endochondral bone is a major architectural component of the cortical bone of the rat (Rattus norvegicus). , 2013, Journal of structural biology.

[11]  Emmanuel Brun,et al.  PyHST2: an hybrid distributed code for high speed tomographic reconstruction with iterative reconstruction and a priori knowledge capabilities , 2013, ArXiv.

[12]  F. Rustichelli,et al.  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 , 2013, Stem cells translational medicine.

[13]  Xianghui Xiao,et al.  A versatile indirect detector design for hard X-ray microimaging , 2012 .

[14]  P. Cloetens,et al.  X-Ray Phase Nanotomography Resolves the 3D Human Bone Ultrastructure , 2012, PloS one.

[15]  R. Cancedda,et al.  Extracellular matrix deposition and scaffold biodegradation in an in vitro three‐dimensional model of bone by X‐ray computed microtomography , 2012, Journal of tissue engineering and regenerative medicine.

[16]  Françoise Peyrin,et al.  X-ray in-line phase tomography of multimaterial objects. , 2012, Optics letters.

[17]  S. Mundlos,et al.  Fetal and postnatal mouse bone tissue contains more calcium than is present in hydroxyapatite. , 2011, Journal of structural biology.

[18]  A. Sharir,et al.  Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis , 2011, Development.

[19]  S. Weiner,et al.  Bone mineralization proceeds through intracellular calcium phosphate loaded vesicles: a cryo-electron microscopy study. , 2011, Journal of structural biology.

[20]  Kay Raum,et al.  Spatial-temporal mapping of bone structural and elastic properties in a sheep model following osteotomy. , 2011, Ultrasound in medicine & biology.

[21]  F Witt,et al.  The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments. , 2011, Journal of biomechanics.

[22]  O. Bunk,et al.  Ptychographic X-ray computed tomography at the nanoscale , 2010, Nature.

[23]  Françoise Peyrin,et al.  Regularization of Phase Retrieval With Phase-Attenuation Duality Prior for 3-D Holotomography , 2010, IEEE Transactions on Image Processing.

[24]  P Cloetens,et al.  Regularized phase tomography enables study of mineralized and unmineralized tissue in porous bone scaffold , 2010, Journal of microscopy.

[25]  P. Prendergast,et al.  Developing bones are differentially affected by compromised skeletal muscle formation , 2010, Bone.

[26]  E. Golub Role of matrix vesicles in biomineralization. , 2009, Biochimica et biophysica acta.

[27]  P. Fratzl,et al.  Spatial and temporal variations of mechanical properties and mineral content of the external callus during bone healing. , 2009, Bone.

[28]  J. W. C. Dunlop,et al.  New Suggestions for the Mechanical Control of Bone Remodeling , 2009, Calcified Tissue International.

[29]  Francoise Peyrin,et al.  X-ray synchrotron radiation pseudo-holotomography as a new imaging technique to investigate angio- and microvasculogenesis with no usage of contrast agents. , 2009, Tissue engineering. Part C, Methods.

[30]  M. Ho Ba Tho,et al.  Relationships between density and Young's modulus with microporosity and physico-chemical properties of Wistar rat cortical bone from growth to senescence. , 2008, Medical engineering & physics.

[31]  F Peyrin,et al.  Kinetics of in vivo bone deposition by bone marrow stromal cells within a resorbable porous calcium phosphate scaffold: An X‐ray computed microtomography study , 2007, Biotechnology and bioengineering.

[32]  S. Judex,et al.  Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  F Peyrin,et al.  Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium phosphate bioceramic: evidence for a coupling between bone formation and scaffold resorption. , 2007, Biomaterials.

[34]  M. Mastrogiacomo,et al.  Tissue engineering of bone: search for a better scaffold. , 2005, Orthodontics & craniofacial research.

[35]  Thomas Lufkin,et al.  Genetic Variation in Bone Growth Patterns Defines Adult Mouse Bone Fragility , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  P. Cloetens,et al.  Optimization of phase contrast imaging using hard x rays , 2005 .

[37]  T. Bateman,et al.  Bone development and age-related bone loss in male C57BL/6J mice. , 2003, Bone.

[38]  Françoise Peyrin,et al.  Quantification of the degree of mineralization of bone in three dimensions using synchrotron radiation microtomography. , 2002, Medical physics.

[39]  S. Wilkins,et al.  Simultaneous phase and amplitude extraction from a single defocused image of a homogeneous object , 2002, Journal of microscopy.

[40]  L. Donahue,et al.  Postnatal and Pubertal Skeletal Changes Contribute Predominantly to the Differences in Peak Bone Density Between C3H/HeJ and C57BL/6J Mice , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[41]  P. Cloetens,et al.  Holotomography: Quantitative phase tomography with micrometer resolution using hard synchrotron radiation x rays , 1999 .

[42]  P Cloetens,et al.  A synchrotron radiation microtomography system for the analysis of trabecular bone samples. , 1999, Medical physics.

[43]  Gilles Peix,et al.  Hard x-ray phase imaging using simple propagation of a coherent synchrotron radiation beam , 1999 .

[44]  A. Snigirev,et al.  On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation , 1995 .

[45]  A. Momose,et al.  Phase-contrast radiographs of nonstained rat cerebellar specimen. , 1995, Medical physics.

[46]  Klaus Klaushofer,et al.  Nucleation and growth of mineral crystals in bone studied by small-angle X-ray scattering , 1991, Calcified Tissue International.

[47]  A. Sharir,et al.  A temporary decrease in mineral density in perinatal mouse long bones. , 2013, Bone.

[48]  H. Birkedal,et al.  Calcified Cartilage Islands in Rat Cortical Bone , 2012, Calcified Tissue International.

[49]  G. N. Duda,et al.  The spatio-temporal arrangement of different tissues during bone healing as a result of simple mechanobiological rules , 2012, Biomechanics and modeling in mechanobiology.

[50]  J. R. Scotti,et al.  Available From , 1973 .