ASA PRESSROOM


Acoustical Society of America
159th Meeting Lay Language Papers


[ Lay Language Paper Index | Press Room ]


Listen to Bone Quality: How Ultrasound Helps to Reveal Microstructure and Elastic Function in Bone

 

Kay Raum - kay.raum@charite.de

Julius Wolff Institute & Berlin-Brandenburg School for Regenerative Therapies

Charit - Universittsmedizin Berlin

Augustenburger Platz 1

13353 Berlin, Germany

 

Quentin Grimal - quentin.grimal@upmc.fr

Laboratoire dImagerie Paramtrique

CNRS, Universit Pierre et Marie Curie-Paris 6

F75006 Paris, France

 

Alf Gerisch - gerisch@mathematik.tu-darmstadt.de

Fachbereich Mathematik

Technische Universitt Darmstadt

Dolivostr. 15

64293 Darmstadt, Germany

 

Pascal Laugier - pascal.laugier@upmc.fr

Laboratoire dImagerie Paramtrique

CNRS, Universit Pierre et Marie Curie-Paris 6

F75006 Paris, France

 

Popular version of paper 5pBB9

Presented Friday afternoon, April 23, 2010

159th ASA Meeting, Baltimore, MD

 

 

Introduction

 

Sophisticated technical materials that are used in everyday life are often inspired by nature. Lightweight honeycomb constructions and carbon fiber reinforced sandwich composites, for example, are used to construct airplanes, cars or modern sports equipment and aim to optimize various properties, e.g. weight, toughness and strength that cannot be achieved by a single material. Examples of adopting structural concepts from nature for the design of technical materials and the construction of devices date back centuries, to the first concept of a flying machine by Leonardo da Vinci in 1488. However, our current knowledge about natural concepts to achieve a desired function is still limited and the investigation of functional consequences of specific design variations is the focus of the rather young and growing research discipline, called Biomimetics.

 

Hard biological tissues, e.g. mineralized tendons, bone and teeth are natural examples of achieving unique combinations and also great variability of stiffness and strength. All of these tissues have a common building block a collagen fibril that is reinforced by small mineral crystals. One of the striking features of these tissues is the ability to adapt to variable loading conditions by multiple but well organized structural arrangements of this building block at several levels of hierarchical organization (Fig. 1).

 

 

Figure 1. Hierarchical structure of compact bone: a) compact bone in long diaphysis; b) osteons formed by lamellae; c) bone lamellae, made of a sandwich compound of mineralized collagen fibril films with variable orientations; d) film of mineralized collagen fibrils with a single orientation e) basic building block: the mineralized collagen fibril; f) extra-fibrillar matrix. From Reisinger et al. [1].

 

For survival, the skeleton of animals and humans has to provide stability, support and protection of the internal organs against mechanical impacts in combination with the ability of fast and energy efficient locomotion that is needed to collect food, hunt or escape from other hunting animals. Moreover, this functionality has to be preserved throughout lifetime, which requires adaptation to variable conditions during maturation and ageing, but also repair mechanisms that allow both, an incremental repair of microdamage and restoration of macroscopic defects, i.e. fractures.

 

In order to achieve these goals, bone uses various design concepts, e.g. reinforcing a soft and flexible collagen matrix by stiff, but brittle mineral particles, sandwich compounding of anisotropic (directional) films, weight reduction by directional pores and spongy networks. Adaptation and repair is realized by an army of cells specialized either in sensing, mining or construction of bone tissue. Altogether this leads to a highly dynamic, lightweight stiff and tough compound material that is usually able to maintain its function throughout lifetime.

This principle of bone adaptation is widely accepted as Wolffs law of bone adaptation based on the classic work of Julius Wolff entitled Das Gesetz der Transformation der Knochen (The Law of Transformation of Bone), published in 1892 [2]. Since then mechanical properties of bone have been intensively investigated by macroscopic to nanoscopic mechanical testing, imaging and numerical approaches.

 

Although many details of the genetics, biology, pathology and mechanics of bone have been uncovered, we still lack of a detailed understanding of bone structure at the nano- and microscales. Existing theoretical bone models only allow us a limited description of macroscopic function (e.g. stability and resistance to failure) based on structural and compositional features at smaller hierarchical levels of organization. However, such models are crucial, e.g. to i) understand the mechanical and biological mechanisms of bone adaptation, ii) predict the outcome of anabolic (bone building) or antiresorptive treatment strategies, iii) define design concepts for technical materials with equally good combinations of properties like bone and iv) provide a better understanding of the origin of the mechanical resistance properties of bones. The latter is of particular importance, as it would help researchers to design a new class of non-invasive, non-ionizing, ultrasound based diagnostic systems that would allow for a safe and reliable prediction and monitoring of fracture risk and fracture healing.

 

Towards this goal, both experimental data of heterogeneous elastic and structural parameters from all length scales (from the centimeter to the nanometer scale) and theoretical models that can simulate the deformation behavior based on these data are required.

 

 

Quantitative Ultrasound

 

If sound waves propagate through a material, their elastic interactions cause small reversible deformations (compression, expansion, or shearing). The velocities of these deformations are determined by the elastic properties and the mass density of the material. This principle has been used for decades for the non-invasive and nondestructive evaluation of technical materials and biological tissues [3-6]. Focused ultrasound transducers that emit short pulses and measure the reflection amplitude can be used like a virtual fingertip to probe the elastic response of the surface of a material. By scanning the transducer over the surface, elastic maps can be obtained. The size of this virtual fingertip depends upon the numerical aperture of the sound field and the acoustic frequency, and can be varied over several orders of magnitude (from 10 mm at 100 kHz down to 0.5 m at 2 GHz) [7-14].

 

 

Figure 2. Acoustic images (top) and numerical models (bottom) of human bone cross-sections. The gray-scale in the acoustic images corresponds to the local elastic response of the tissue to the incoming wave (bright = stiff; dark = soft). From left to right: Ultrasound in the GHz range reveals the apparent sandwich compound structure of fibril bundles. The large dark spot is a Haversian canal hosting blood vessels and the small spots are osteocyte lacunae, hosting bone cells. These data (in combination with other input data) are used to construct the fibril, lamellar, and osteon models. At 200 MHz parallel and elliptical tissue structures (osteons) as well as a porous microstructure can be observed. These data are the basis for the tissue model.

 

 

The Bottom-up Approach

 

A bottom-up approach requires experimentally assessed structural, compositional and elastic data at each hierarchical level of organization from the nanoscale to the macroscale (Fig. 2). These data can be obtained by ultrasound with the frequency tuned to the structural dimension at each hierarchy level and site-matched complementary data (e.g. mineralization from synchrotron radiation micro computed tomography (SR-CT) [7, 8, 10, 11]. Simplified volume elements that resemble the major structural design features, but also incorporate degrees of freedom for dynamic adaptation (e.g. a time-dependent change of mineralization) can then be constructed (Fig. 2). The effective elastic properties of such volume elements can be computed by numerical homogenization approaches [15, 16]. For example, the data can be translated into a so-called Finite Element (FE) mesh. By numerical deformation analyses, i.e. a virtual compression and calculation of the resulting deformation, the elastic parameters that describe a similarly behaving homogeneous material, i.e. a material without any structure or variation of material properties, can be derived.

 

Homogenization from the nano- to the macroscale is performed in a series of steps: the effective material properties obtained at one hierarchical level are used to build the volume element at the next scale. The advantage of this approach is a dramatic reduction of complexity without the loss of structure-functional relationships. Furthermore, experimental data at a given next length scale serve both for the validation of the homogenization model and as input for the next homogenization step.

 

 

Results

 

We have derived the elastic stiffness parameters, i.e. the elastic stiffness tensor and the degree of mineralization in human cortical bone at several length scales by site-matched Scanning Acoustic Microscopy (SAM) and SR-CT. From these data, hierarchical models have been developed that connect the nanoscale with the macroscale (Fig. 2) and describe the elastic behavior of the tissue at all length scales. Our results indicate that some of the previously proposed fibril arrangements at the nanoscale [17] do not result in the experimentally observed elastic properties at the next length scale (microscale). However, our data support the model of a twisted plywood structure [18, 19]. This model uses only a simple construction rule, but allows in principle the design of several previously reported fibril arrangements by a variation of the thickness of individual fibril layers. At the next length scale (mesoscale), the effects of material properties and the porous network have been evaluated numerically. Moreover, local variations of the mesoscale structural and elastic properties within the femoral shaft appear to be related to an inhomogeneous strain distribution resulting from external (macroscopic) stresses by weight and muscle forces.

 

 

Conclusion

 

Ultrasound provides a unique and to date almost unexplored way to listen to bone quality. In contrast to other mechanical or imaging techniques, this ultrasound-based elastic imaging approach combines the possibility to assess structural and material properties of the tissue across multiple length scales. In order to handle this complex information, established engineering tools, e.g. finite element analyses and homogenization techniques have been employed. By utilizing such a combination, the principal mechanisms leading to the exceptional combination of toughness and strength, as well as the change of these properties throughout the course of bone ageing or pathologies, can be investigated.

 

 

Acknowledgments

 

This work has been conducted within the European Associated Laboratory Ultrasound Based Assessment of Bone (ULAB) and was supported by the Deutsche Forschungsgemeinschaft within the priority program SPP1420 Biomimetic Materials Research: Functionality by Hierarchical Structuring of Materials (grant Ra1380/7).

 

 

References

 

[1] Reisinger,A.G., Pahr,D.H., Zysset,P.K., Sensitivity analysis and parametric study of elastic properties of an unidirectional mineralized bone fibril-array using mean field methods, Biomech. Model. Mechanobiol. 2010.

 

[2] Wolff,J., Das Gesetz der Transformation der Knochen. Berlin, Verlag von August Hirschwald. 1892.

 

[3] Ashman,R.B., Cowin,S.C., Rho,J.Y., Van Buskirk,W.C., Rice,J.C., A continous wave technique for the measurement of the elastic properties of cortical bone, J. Biomech. 17 (5), 1984, 349-361.

 

[4] Lees,S., Heeley,J.D., Cleary,P.F., A study of some properties of a sample of bovine cortical bone using ultrasound, Calcif. Tissue Int. 29 (2), 1979, 107-117.

 

[5] Rho,J.Y., An ultrasonic method for measuring the elastic properties of human tibial cortical and cancellous bone, Ultrasonics 34 (8), 1996, 777-783.

 

[6] Van Buskirk,W.C., Cowin,S.C., Ward,R.N., Ultrasonic measurement of orthotropic elastic constants of bovine femoral bone, J. Biomech. Eng. 103 (2), 1981, 67-72.

 

[7] Raum,K., Microelastic imaging of bone, IEEE Trans. Ultrason. , Ferroelect. , Freq. Contr. 55 (7), 2008, 1417-1431.

 

[8] Raum,K., Hofmann,T., Leguerney,I., Saied,A., Peyrin,F., Vico,L., Laugier,P., Variations of microstructure, mineral density and tissue elasticity in B6/C3H mice, Bone 41 (6), 2007, 1017-1024.

 

[9] Raum,K., Kempf,K., Hein,H.J., Schubert,J., Maurer,P., Preservation of microelastic properties of dentin and tooth enamel in vitro--a scanning acoustic microscopy study, Dent. Mater. 23 (10), 2007, 1221-1228.

 

[10] Raum,K., Leguerney,I., Chandelier,F., Talmant,M., Saied,A., Peyrin,F., Laugier,P., Site-matched assessment of structural and tissue properties of cortical bone using scanning acoustic microscopy and synchrotron radiation CT, Phys. Med. Biol. 51 (3), 2006, 733-746.

 

[11] Hofmann,T., Heyroth,F., Meinhard,H., Franzel,W., Raum,K., Assessment of composition and anisotropic elastic properties of secondary osteon lamellae, J Biomech. 39 (12), 2006, 2284-2294.

 

[12] Hube,R., Mayr,H., Hein,W., Raum,K., Prediction of biomechanical stability after callus distraction by high resolution scanning acoustic microscopy, Ultrasound Med. Biol. 32 (12), 2006, 1913-1921.

 

[13] Raum,K., Leguerney,I., Chandelier,F., Bossy,E., Talmant,M., Saied,A., Peyrin,F., Laugier,P., Bone microstructure and elastic tissue properties are reflected in QUS axial transmission measurements, Ultrasound Med. Biol. 31 (9), 2005, 1225-1235.

 

[14] Raum,K., Jenderka,K.V., Klemenz,A., Brandt,J., Multilayer analysis: Quantitative scanning acoustic microscopy for tissue characterization at a microscopic scale, IEEE Trans. Ultrason. , Ferroelect. , Freq. Contr. 50 (5), 2003, 507-516.

 

[15] Parnell,W.J., Grimal,Q., The influence of mesoscale porosity on cortical bone anisotropy. Investigations via asymptotic homogenization, J R. Soc. Interface 6 (30), 2009, 97-109.

 

[16] Grimal,Q., Raum,K., Gerisch,A., Laugier,P., Derivation of the mesoscopic elasticity tensor of cortical bone from quantitative impedance images at the micron scale, Comput. Methods Biomech. Biomed Engin. 11 (2), 2008, 147-157.

 

[17] Wagermaier,W., Gupta,H.S., Gourrier,A., Burghammer,M., Roschger,P., Fratzl,P., Spiral twisting of fiber orientation inside bone lamellae, Biointerphases 1 (1), 2006, 1-5.

 

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

 

[19] Giraud-Guille,M.M., Twisted plywood architecture of collagen fibrils in human compact bone osteons, Calcif. Tissue Int. 42 (3), 1988, 167-180.