Diagnostic ultrasound imaging has gained wide acceptance for a broad range of clinical uses. In many cases, ultrasonography is the first-line imaging modality selected for its ease of access and absence of ionizing radiation. Over the last decades, ultrasonography has considerably evolved and is currently contributing to important improvements in patient diagnosis and treatment. Modern ultrasound imaging can provide soft tissue anatomical (shape, size…) and functional information (tissue movements, blood flow) in 3D and 4D, characterization and distinction among tissues (echostructure) and quantification of tissue properties (microstructure, tissue stiffness). Soft tissue quantitative ultrasound (QUS) refers to methods specifically developed to assess quantitative variables reflecting tissue physical properties, usually by analyzing the raw radiofrequency signals and/or its spectral characteristics.

Bone QUS methods were introduced in the 1970s to assess bone loss in the context of osteoporosis, a disease characterized by a decreased bone mass and a deteriorated bone microstructure, resulting in reduced bone strength, elevated bone fragility and increased fracture risk. At that time, the demand for measurement of skeletal status to identify subjects who could be exposed to an increased risk of fracture was rapidly increasing. Safe, easy-to-use, radiation-free, and portable QUS techniques were rapidly developed and were thought to be particularly indicated to assess bone status and to complement X-ray based densitometry techniques. Bone QUS has been a vivid research field. 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 were reported. A first book entitled Bone QUS (https://www.springer.com/fr/book/9789400700161) has been published in 2011. In almost ten years from 2011 to 2021, significant progress and growth in quantitative ultrasound techniques could be seen. From the development of new procedures and techniques to new devices and new applications, QUS is continuing to increase our knowledge about bone elastic properties and contribute a major impact to clinical diagnosis. We feel that it is timely to bring together in one book the most recent research.

This book Bone quantitative ultrasound: new horizons reflects the current status of the research and is intended to be a complement to the first book, rather than a second edition, in the sense that basic notions already presented in the first book will not be repeated here.

The physics of ultrasound propagation in bone (a hard tissue) substantially differs from the propagation in soft tissues. It involves shear waves coupled to longitudinal waves, guided waves, strong scattering effects, strong attenuation and velocity dispersion. This complex physics has hampered a fast development of bone QUS but the engineer can also take advantage of this rich physics to design specific methods to probe bone properties. For instance, guided waves carry important diagnostic information on cortical thickness, porosity and elastic properties; shear waves may provide complementary information to longitudinal waves on material properties; poroelasticity is a rich framework to interpret ultrasound propagation in trabecular bone and extract microstructural parameters; frequency-dependent backscattering is successfully used to probe microstructural features of trabecular and cortical bone. In this book, many examples of the use of this rich physics to measure bone properties are presented, together with pragmatic approaches relying on empirical correlations between osteoporosis biomarkers and ultrasound quantities.

Bone QUS has progressed taking advantage of improvements in transducer technology, electronics, availability of ultrasound open platforms and increase in computer power. B-mode cortical bone imaging, measurement of bone vascularization, bone tomography coupled to full waveform inversion open up new horizons for the bone QUS research field. Machine learning is increasingly being used to process raw radio-frequency signals for the quantification of bone properties and for classification of patients. Also, during the last decade, new devices appeared on the market and new approaches to quantify microstructure have been further developed. Finally, a large amount of data documenting the mechanical and acoustical properties of bone, a keystone to the development of bone QUS, have recently been made available.

The bone QUS research community brings together individuals from various backgrounds, i.e., acoustics, medical imaging, biomechanics, biomedical engineering, applied mathematics, bone biology and clinical sciences. This book is intended for the researchers, graduate or undergraduate students, engineers and clinicians from these backgrounds. It presents the most recent experimental results, theoretical concepts and technologies developed so far, together with recent clinical results. The book chapters are organized in three parts as detailed below.

Part I is devoted to ultrasound methods developed for the diagnosis of osteoporosis. It collects chapters describing methods to assess cortical and trabecular bone status and their clinical applications. Chapters 2 and 3 present the generic measurement methods implemented in currently available bone clinical ultrasound devices. They describe the state-of-the art devices, their practical use and clinical performance, and the current clinical consensus. Chapters 4 and 5 deal with ultrasound guided waves in cortical bone. This topic represents a significantly growing area in the past decade and it has sparkled intense research in both instrumentation and signal processing. Instrumentation and signal processing techniques are presented in detail altogether with the most recent clinical results as example. These chapters also describe in details the models that are used to solve the direct problem and strategies that are currently developed to solve the inverse problem. Chapter 6 presents the most recent results together with the most recent clinical findings exploiting the two-wave phenomenon predicted by Biot theory of poroelastic media. Chapters 7, 8, and 9 present general principles for measuring ultrasound scattering and cover recent progress in understanding and measuring scattering from cancellous and cortical bone. The goal of these chapters is to give the reader an extensive view of the scattering interaction mechanisms as an aid to understand the QUS potential and the types of variables that can be determined by QUS scattering in order to characterize bone microstructure. Metrics can be calculated from the radio frequency signals measured in pulse echo mode, which demonstrate empirical correlation with bone mineral density. These metrics serve as a basis for the in vivo evaluation of osteoporosis at the hip and spine (Chap. 7) or at the calcaneus (Chap. 8). A new approach to characterize cortical bone microstructure (porosity, pore size) based on ultrasound scattering is presented in Chap. 9. To conclude Part I, Chaps. 10 and 11 cover cutting-edge researches still at an early development stage but presenting an exciting potential for clinical applications. Chapter 10 unveils recent advances in real-time quantitative imaging of cortical bone and measurement of cortical blood vascularization. Chapter 11 describes quantitative ultrasound tomography of cortical bone. These imaging techniques exploit experimental and signal processing approaches inspired from the methods well-known from seismologists to image Earth.

Chapters 12, 13, 14, and 15 of Part II focus on bone material properties, such as elasticity and piezoelasticity. Resonant ultrasound spectroscopy (RUS), a method recently introduced in the bone field to measure the anisotropic stiffness tensor of cortical bone with the aim to become a standard measurement device in the lab, is presented in details in Chap. 12. Chapters 13 and 14 summarize the most recent results of elasticity measured with RUS or the time of flight technique from hundreds of bone specimens harvested from several skeletal sites of adults and children. These data provide and unprecedented collection of anisotropic elasticity and speed of sound values of hard tissues that are of fundamental interest for bone biomechanics and bone QUS. Interesting piezoelectric and opto-acoustic properties of bone are discussed in Chap. 15 together with details of the measurement techniques.

Although the issue of osteoporosis and biomechanics are still the main motivation for developing bone QUS and occupies a central place in the book, thus reflecting the status of the research in the past 10 years, we wanted to broaden the horizon with Chaps. 16, 17, 18, and 19 of Part III by including new exciting topics which receive some attention as clinical tools. Chapter 16 presents three-dimensional ultrasound imaging of the spine allowing large-scale screening to diagnose scoliosis. Chapter 17 describes recent developments of quantitative ultrasound methods to investigate implant anchorage with a focus on dental implants. Acoustic properties of the skull are increasingly being investigated in the context of brain imaging and therapy. One methodology to efficiently focus ultrasound in the brain accounting for skull properties is presented in Chap. 18. The physics of ultrasound guided waves in the skull and the opportunities of using these for imaging and therapy are discussed in Chap. 19. Hopefully, the light shed on these techniques which are still unfamiliar in the bone field will be enriching and, together with the knowledge accumulated in bone QUS in the past 25 years, may help to produce constructive and ongoing interactions among all fields. We believe that the book (together with the previous one) will provide a comprehensive overview of the methods and principles used in bone quantitative ultrasound and will be an invaluable resource for all novice or experienced researchers in the field.