Bone Quantitative Ultrasound: New Horizons (Advances in Experimental Medicine and Biology, 1364)

Many significant achievements in new ultrasound technologies to measure bone and models to elucidate the interaction and the propagation of ultrasonic waves in complex bone structures have been reported over the past ten years. Impaired bone remodeling affects not only the trabecular compartment but also the cortical one. Despite the crucial contribution of the cortical structure to the whole bone mechanical competence, cortical bone was understudied for a long time. A paradigm shift occurred around 2010, with a special focus placed on the importance of cortical bone. This has sparkled a great deal of interest in new ultrasound techniques to assess cortical bone. While our book ‘Bone Quantitative Ultrasound'published in 2011 emphasized techniques to measure trabecular bone, this new book is devoted for a large part to the technologies introduced recently to measure cortical bone. These include resonant ultrasound spectroscopy, guided waves, scattering, and pulse-echo and tomographyimaging techniques. Instrumentation, signal processing techniques and models used are detailed. Importantly, the data accumulated in recent years such as anisotropic stiffness, elastic engineering moduli, compression and shear wave speeds of cortical bones from various skeletal sites are presented comprehensively. A few chapters deal with the recent developments achieved in quantitative ultrasound of trabecular bone. These include (i) scattering-based approaches and their application to measure skeletal sites such as the spine and proximal femur and (ii) approaches exploiting the poro-elastic nature of bone. While bone fragility and osteoporosis are still the main motivation for developing bone QUS, this Book also includes chapters reporting ultrasound techniques developed for other applications of high interest such as 3-D imaging of the spine, assessment of implant stability and transcranial brain imaging. This book, together with the book ‘Bone Quantitative Ultrasound'published in 2011 will provide a comprehensive overview of the methods and principles used in bone quantitative ultrasound and will be a benchmark for all novice or experienced researchers in the field. The book will offer recent experimental results and theoretical concepts developed so far and would be intended for researchers, graduate or undergraduate students, engineers, and clinicians who are involved in the field. The book should be considered as a complement to the first book publisher in 2011, rather than a second edition, in the sense that basic notions already presented in the first book are not repeated. Foreword Lessons from the Past Prospects for the Future Contents 1 Introduction Part I Ultrasound Methods for Skeletal Status Clinical Assessment 2 Quantitative Ultrasound (QUS) in the Management of Osteoporosis and Assessment of Fracture Risk: AnUpdate 2.1 Osteoporosis: The Clinical Problem 2.1.1 The Skeleton and Bone Tissue 2.1.2 Defining Osteoporosis 2.1.3 The Hallmark of Osteoporosis: Fracture 2.1.4 Osteoporosis Diagnosis and Treatment 2.2 Quantitative Ultrasound: The Principles and the Method 2.2.1 The Basics 2.2.2 QUS Devices 2.2.2.1 Trabecular Transverse Transmission 2.2.2.2 Cortical Transverse Transmission 2.2.2.3 Cortical Axial Transmission 2.2.2.4 Pulse-Echo Measuring Devices 2.2.3 QUS Advantages over DXA 2.3 QUS Use in Osteoporosis Fracture Risk Prediction 2.3.1 QUS Heel Devices (Trabecular Transverse Transmission) 2.3.2 QUS Radius Devices (Cortical Axial Transmission) 2.3.3 QUS Other Devices 2.3.4 QUS Incorporation into the Clinical Routine of Osteoporosis Management 2.4 Conclusions Compliance with Ethical Standards References 3 Clinical Devices for Bone Assessment 3.1 Introduction 3.2 Trabecular Transverse Transmission (Tr.TT) 3.2.1 Broadband Ultrasound Attenuation (BUA) 3.2.2 Speed of Sound 3.2.3 Bone Stiffness and Quality Surrogates 3.3 Cortical Transverse Transmission 3.4 Cortical Axial Transmission 3.5 Cortical Pulse-Echo 3.6 Trabecular Pulse-Echo 3.7 What Has Been Achieved and What Is Still Missing in Bone QUS? References 4 Axial Transmission: Techniques, Devices and ClinicalResults 4.1 Introduction 4.2 Background 4.3 Methods 4.3.1 Ultrasonic Measuring Device 4.3.2 Dedicated Signal Processing: Features Extraction 4.3.3 Waveguide Modeling 4.3.3.1 Inverse Waveguide Model 4.3.3.2 Overview of Advanced Waveguide Models 4.3.4 Inverse Problem Based on Multimode Guided Waves 4.3.4.1 General Framework: A Genetic Algorithm-Based Identification 4.3.4.2 Specific Inverse Framework Towards Clinical Applications 4.4 Main Achievements 4.4.1 Inverse Characterization of Multiple Cortical Bone Properties 4.4.2 Impact of Soft Tissue on Cortical Bone Estimates 4.4.3 Ex Vivo Validation of Cortical Bone Quality Markers 4.4.4 Towards Clinical Applications 4.5 Summary and Outlook 4.6 Looking Ahead References 5 Signal Processing Techniques Applied to Axial Transmission Ultrasound 5.1 Introduction 5.2 Single Transmitter-Receiver Configuration 5.2.1 Dispersion Imaging 5.2.2 Modal Filtering 5.3 Multiple Transmitter-Receiver Configuration 5.3.1 Dispersion Imaging and Filtering 5.3.2 Dispersion Inversion 5.3.3 Artificial Intelligence Applications 5.4 The Road Ahead References 6 Ultrasonic Assessment of Cancellous Bone Based on the Two-Wave Phenomenon 6.1 Investigation of the Ultrasonic Two-Wave Phenomenon 6.1.1 Overview of the Cancellous Bone Ultrasonic Measurement 6.1.2 Biot's Theory and Two Longitudinal Waves 6.1.3 Fast and Slow Wave Acoustic Characteristics 6.2 Simulation of Ultrasound Propagation and the Numerical Techniques of Extracting Valuable Information from the Waveforms 6.2.1 Elastic FDTD Method 6.2.2 Simulation Using Real Bone Models Derived by Micro-CT 6.2.3 The Effect of Cortical Bone Layer and Physical Parameters 6.2.4 Mathematical Method to Derive Quantitative Information from the Measured Waveforms 6.2.5 Simulations Using Digitally Modified Models and Artificially Created Models 6.3 In Vivo Application of the Ultrasonic Two-Wave Phenomenon 6.3.1 Outline of LD-100 6.3.2 Clinical Study Results for LD-100 6.3.2.1 Comparison with X-Ray pQCT 6.3.2.2 Discrimination Ability for Fractures 6.3.2.3 Cohort Study 6.3.2.4 Relationship with Lifestyle-Related Disease 6.3.2.5 Athlete 6.3.2.6 Young People 6.3.2.7 Future Work 6.4 Conclusion References 7 Pulse-Echo Measurements of Bone Tissues. Techniques and Clinical Results at the Spine and Femur 7.1 Novel Approaches for Echographic Evaluation of Osteoporosis on Proximal Hip and Lumbar Spine 7.1.1 Introduction 7.1.2 Novel Radiofrequency Echographic Multi Spectrometry (REMS) Approach for Hip and Spine 7.2 Insights into REMS Technology 7.2.1 Overview 7.2.1.1 Osteoporosis Score 7.2.1.2 Fragility Score 7.2.2 Osteoporosis Score Calculation 7.2.2.1 Overview of the Methodology 7.2.3 Fragility Score Calculation 7.2.3.1 Overview of the Adopted Method 7.2.3.2 Construction of the Reference Database 7.2.3.3 Calculation of the Fragility Score 7.3 Clinical Studies 7.3.1 Comparison Between REMS and DXA for Osteoporosis Diagnosis 7.3.2 REMS for Fracture Risk Prediction 7.3.3 Therapeutic Monitoring 7.3.4 Application to Arthrosis 7.3.5 Management of Bone Artifacts 7.3.6 Osteoporosis in Pregnancy 7.3.7 Fragility Score: Ability to Identify Frail Patients 7.4 Conclusion and Future Perspectives Compliance with Ethical Standards References 8 Scattering in Cancellous Bone 8.1 Fundamental Scattering Mechanisms in Cancellous Bone 8.2 Recent Advances in Understanding of Scattering from Cancellous Bone 8.2.1 Scattering Metrics 8.2.2 Single Scattering 8.2.3 Multiple Scattering 8.2.3.1 Multiple Scattering at Frequencies Below 1 MHz 8.2.3.2 Multiple Scattering at Frequencies Above 1 MHz 8.3 Recent Clinical Applications of Scattering from Cancellous Bone 8.4 Conclusion References 9 Ultrasound Scattering in Cortical Bone 9.1 Introduction 9.1.1 The Need for a Non-invasive Assessment of Microstructural Porosity 9.1.2 Leveraging Scattering by the Microstructure 9.2 Ultrasound Attenuation and Its Relationship to Scattering 9.2.1 Frequency-Dependent Attenuation in Cortical Bone Depends on the Microstructure of Cortical Porosity 9.2.2 Phenomenological Power Law Model 9.2.3 Physics-Based Model Accounting for Scattering 9.2.4 The Effect of Absorption 9.3 Backscatter Coefficient 9.3.1 Using Backscatter to Assess Porosity 9.3.2 Using Backscatter to Assess Microstructural Porosity Parameters 9.4 Diffusivity and Multiple Scattering 9.4.1 Context and Rationale 9.4.2 Evaluating the Diffusion Constant from Backscatter Measurements 9.4.3 Diffusivity and Cortical Microstructure 9.5 Challenges and Potential References 10 Single-Sided Ultrasound Imaging of the Bone Cortex: Anatomy, Tissue Characterization and Blood Flow 10.1 Introduction 10.2 Why Does Conventional Ultrasonography Fail to Image the Inside of a Bone? 10.3 Elastic Anisotropy of Cortical Bone and Wave-Speed Anisotropy 10.4 Transmission and Reflection of a Pulsed Wave in the Cortex of a Bone 10.5 Image Reconstruction with Unfocused Transmit Beams 10.6 Real-Time Imaging of the Bone Cortex 10.6.1 Choice of the Reconstruction Technique 10.6.2 Model of Weak Transverse Isotropy 10.7 The Autofocus Method for Measuring the Wave-Speed in a Layered Medium 10.7.1 Principle of the Autofocus Method 10.7.2 Point Scatterer or Interface? 10.7.3 Coherent or Incoherent Compounding? 10.7.4 Application to Cortical Bone: Measurement of P-Wave and SV-Wave Velocity Anisotropy 10.8 Measuring Intracortical Blood Flow with Ultrasound Imaging 10.9 Conclusion References 11 Ultrasound Computed Tomography 11.1 Introduction 11.2 Linear Qualitative USCT 11.2.1 Qualitative Imaging 11.2.2 Reconstruction from Radial Cross-Sections 11.2.3 Elliptical Kernel 11.2.4 Acoustic and Elastic Object Functions 11.2.5 Hard Biological Tissue Imaging 11.2.6 Adapted Signal Processing 11.2.7 Adapted Image Processing 11.2.8 Precision Analysis for 2D Inverse Scattering 11.3 Non-linear Quantitative USCT 11.3.1 Compound-Mode USCT 11.3.2 Intercepting Canonical Body Approximation (ICBA) 11.3.3 Full-Waveform Inversion (FWI) Algorithms 11.4 Conclusion References Part II Ex Vivo Measurement of Bone Material Properties: New Methods and Data 12 Measurement of Cortical Bone Elasticity Tensor with Resonant Ultrasound Spectroscopy 12.1 Introduction 12.1.1 A Brief Historical Review of RUS 12.2 Computation of the Resonant Frequencies 12.2.1 The Rayleigh-Ritz Method 12.2.2 Application to a Rectangular Parallelepiped 12.2.3 An Alternative: The Finite Element Method 12.3 Specimen Preparation and Measurement Setup 12.3.1 Cutting the Specimens 12.3.2 Processing of the Specimens After Cutting 12.3.3 Measurement of the Frequency Response of the Sample 12.4 Signal Processing 12.4.1 Estimation of the Resonant Frequencies in Time Domain 12.4.2 Non-linear Fitting in Frequency Domain 12.4.3 Combining Data from Multiple Spectra 12.4.4 Other Methods: Bayesian Analysis and Empirical Mode Decomposition 12.5 Inverse Problem 12.5.1 Bayesian Formulation of the Inverse Problem: Posterior Probability Density Function 12.5.2 Sampling the Posterior Distribution 12.5.3 Building a priori on the Elastic Parameters 12.5.4 Posterior Distribution Analysis 12.6 Validation of RUS for Bone Stiffness Measurement 12.7 Viscoelasticity 12.7.1 Link Between Peak Width and Viscoelasticity 12.7.2 Analysis Based on the First Resonant Mode 12.7.3 Anisotropic Analysis of Some Selected Specimens 12.8 Conclusion Appendix: Anisotropic Elasticity References 13 Documenting the Anisotropic Stiffness of Hard Tissues with Resonant Ultrasound Spectroscopy 13.1 Introduction 13.2 A Historical Review of RUS Measurement of Hard Tissues 13.3 Comparative Study 13.3.1 Specimen Information and RUS Measurements 13.3.2 Data Analysis 13.4 Results 13.4.1 Comparison of Tissues' Stiffness and Mass Density 13.4.2 Anisotropy 13.4.3 Correlations with Mass Density 13.5 Discussion 13.6 Conclusion Appendix References 14 Assessing the Elasticity of Child Cortical Bone 14.1 Context and Objectives 14.2 Bone in Children and Adolescents 14.2.1 Bone Growth: A Complex Issue 14.2.1.1 Initial Bone Formation in the Embryo and Fetus 14.2.1.2 Bone Growth in Length and Thickness 14.2.1.3 Bone Remodelling 14.2.1.4 Fracture Repair and Bone Pathologies 14.2.2 Child Cortical Bone, an Elastic and Anisotropic Material 14.2.2.1 Theoretical Background 14.2.3 Challenges in Characterizing Child Cortical Bone with Ultrasound 14.2.3.1 In-vivo vs. in-vitro 14.2.3.2 Scarcity of the Samples 14.2.3.3 Size and Shapes of the Samples 14.3 Methods for Child Bone Elasticity Assessment 14.3.1 Propagation of Elastic Waves 14.3.2 Resonant Ultrasound Spectroscopy 14.4 Elasticity of Child Bone 14.4.1 Adult Bone vs Child Bone 14.4.2 Anisotropy of Child Bone 14.4.3 NPCCB Elasticity and Other Determinants of Bone Strength 14.4.3.1 Correlations with Age 14.4.3.2 Correlations with Microstructure 14.4.3.3 Correlations with Compression Elastic Modulus 14.4.3.4 Correlations with Biochemistry Properties 14.5 Conclusion and Perspectives References 15 Piezoelectric and Opto-Acoustic Material Propertiesof Bone 15.1 Introduction 15.2 Piezoelectric (Electromechanical) Effects in Low Frequency Range 15.2.1 Discovery of Piezoelectricity in Bone 15.2.2 Origin of Piezoelectricity in Bone 15.2.3 Piezoelectric (Electromechanical) Properties in Dry and Wet Bones 15.2.4 Miscellaneous Experiments Involving the Electromechanical Effects 15.2.5 Experimental Methods 15.3 Piezoelectric (Electromechanical) Effects in the High Frequency Range 15.3.1 Electromechanical Effects in Cortical Bone 15.3.2 Electromechanical Effects in Cancellous Bone 15.4 Opto-Acoustic Evaluation of Bone 15.4.1 Photoacoustic Evaluation of Bone 15.4.2 Application of Brillouin Scattering Technique to Bone Evaluation 15.5 Conclusion References Part III Emerging Applications of Bone Quantitative Ultrasound 16 3D Ultrasound Imaging of the Spine 16.1 Introduction 16.2 Related Studies Towards the Production Version of Scolioscan in the Development Stage 16.2.1 Exploration of 3D Ultrasound Using Human Spine Phantom with Conventional Ultrasound System 16.2.2 Pilot Study on AIS Subjects Using Prototype Version of Scolioscan 16.2.3 Design and Procedures Adopted for the Production Version of Scolioscan 16.3 Related Studies Based on the Production Version of Scolioscan 16.3.1 Evaluation of Coronal Curvature of Spine on AIS Subjects 16.3.2 Evaluation of Sagittal Curvature of Spine on AIS Subjects 16.3.3 Assessment on Spinal Flexibility 16.3.4 Changes in Spinal Curvature during Forward Bending 16.3.5 Generation of Coronal Images Using Fast Projection Imaging 16.3.6 Conducting Semi-automatic Measurement on Ultrasound Images 16.3.7 Conducting Automatic Measurement on Ultrasound Images 16.3.8 Performing Automatic Selection for Optimal Ultrasound Images for Evaluation 16.4 Extensive Studies Related to Other Ultrasound System on Human Subjects 16.5 Conclusion References 17 Ultrasonic Evaluation of the Bone-Implant Interface 17.1 Introduction 17.2 QUS Evaluation of a Planar Bone-Implant Interface 17.2.1 Evolution of Bone Peri-Implant Properties During Healing 17.2.2 Influence of Healing Time on the Ultrasonic Response of the BII 17.2.3 Influence of Loading Conditions on the Ultrasonic Response of the BII 17.3 Modeling the Acoustical Behavior of the BII 17.3.1 Macroscopic Roughness 17.3.1.1 Description of the Model 17.3.1.2 Influence of the Implant Roughness and of the Presence of Soft Tissues 17.3.1.3 Influence of Bone Properties 17.3.1.4 Influence of the Central Frequency of the Ultrasonic Wave 17.3.2 Microscopic Roughness 17.3.2.1 Profilometry-Measured Profiles 17.3.2.2 Equivalence with the Sinusoidal Model 17.3.2.3 Analytical Modeling of the BII 17.3.3 Limitations of the Model 17.4 Development of a QUS Device to Assess Dental Implant Stability 17.4.1 Presentation of the QUS Device 17.4.2 Preliminary Studies with Titanium Cylinders 17.4.2.1 In Vitro Study 17.4.2.2 Numerical Simulation 17.4.3 In Vitro Validation on Dental Implants 17.4.3.1 Implants Inserted in Biomaterials 17.4.3.2 Implants Inserted in Bone 17.4.4 Simulation of the Ultrasonic Propagation in Dental Implants 17.4.4.1 Guided Wave Propagation in Dental Implants 17.4.4.2 Influence of Peri-Implant Tissues Properties 17.4.5 In Vivo Validation 17.4.6 Comparison of the Performances of QUS and RFA 17.4.6.1 In Vitro Studies 17.4.6.2 In Vivo Studies 17.5 Conclusion References 18 Adaptive Ultrasound Focusing Through the CranialBone for Non-invasive Treatment of Brain Disorders 18.1 Acoustical Properties of the Skull 18.2 Focusing Ultrasound to the Brain 18.2.1 Concept of Aberration Correction 18.2.2 Non-invasive Correction 18.2.3 Treatment of Brain Disorders Using Focused Ultrasound 18.3 Conclusion References 19 Guided Waves in the Skull 19.1 Introduction 19.2 Generation and Detection 19.2.1 Laser-Triggered Wave Propagation, Near-Field Hydrophone Scan 19.2.2 Wedge-Triggered Wave Propagation 19.2.3 Transmission Immersion Measurements 19.3 Data Processing 19.4 Modeling 19.5 Guided Waves in the Mouse Skull 19.6 Guided Waves in the Human Skull 19.7 Challenges and Outlook References Index