Advanced Bioimaging Technologies in Assessment of the Quality of Bone and Scaffold Materials Techniques and Applications
L. Qin · H.K. Genant J.F. Griffith · K.S. Leung (Editors)
Advanced Bioimaging Technologies in
Assessment of the Quality of Bone and Scaffold Materials
Techniques and Applications
With Figures and Tables
123
Ling Qin
Professor of Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China e-mail: lingqin@cuhk.edu.hk
Harry K. Genant
Professor Emeritus, University of California, San Francisco, Chairman Emeritus; Board of Directors, Synarc, Inc e-mail: harry.genant@radiology.ucsf.ucsf
James F. Griffith
Department of Radiology and Organ Imaging,
The Chinese University of Hong Kong, Hong Kong SAR, China e-mail: Griffith@ruby.med.cuhk.edu.hk
Kwok Sui Leung
Professor of Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China e-mail: ksleung@cuhk.edu.hk
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Foreword (I)
As the Emeritus Professor and Executive Director of the Osteoporosis and Arthritis Research Group of the University of California San Francisco, and as Chairman of the WHO Task Force on Osteoporosis, I am pleased to write this preface to Advanced Bio-imaging Technologies in Assessment of Quality of Bone and Scaffold Biomaterials edited by Ling Qin, Harry K. Genant, James F. Griffith, and Kwok-Sui Leung. This book results largely from the contributions provided by the scientists and physicians who participated in the International Symposium on Advanced Biotechnologies for Assessing Quality of Bone and Scaffold Biomaterials, which was organized by Ling Qin, Ph.D, in Hong Kong, – October, . This unique congress convened the world’s leading researchers and clinicians in the fields of osteoporosis, imaging sciences, and biomechanics.
With the collective knowledge of the participating faculty, it seemed timely and appropriate to assemble this volume, which addresses the advances in imaging and bio-engineering technologies and their applications, and enables researchers and clinicians to examine and understand the pathophysiology of osteoporosis, its natural evolution, and its response to both conventional and novel treatments. These nonin- vasive and/or nondestructive imaging techniques, and the various destructive biome- chanical methods, can provide important structural information about bone beyond standard bone mineral densitometry (BMD). Although BMD provides important in- formation about osteoporosis diagnosis and fracture risk assessment, considerable evidence indicates that BMD only partially explains bone strength and fracture resis- tance. The information obtained from quantitative assessment of macro- and micro- structural characteristics undoubtedly improves our understanding of bone diseases, and enhances our ability to estimate bone strength and predict fractures. The ra- tionale for imaging and biomechanically testing bone macro- and micro-structure, therefore, is to obtain information beyond BMD, improve fracture risk prediction, clarify the pathophysiology of skeletal disease, define the skeletal response to ther- apy, and assess important biomechanical relationships.
Specifically, this book introduces cutting-edge bio-imaging technologies for studying the musculoskeletal system at the molecular level to the organ level, and for examining related biomaterials, including nano- and micro-computed tomogra- phy (CT), peripheral and axial quantitative CT (pQCT and aQCT), magnetic res- onance imaging (MRI), quantitative ultrasound (QUS), transmission and scanning electron microscopy (TEM and SEM), confocal microscopy, polarized and flores- cence microscopy, near-field scanning optical microscopy, scanning acoustic mi- croscopy, cell traction force microscopy, nano-micro-indentation, high-fidelity D microscopy, microradiography, fiber-optic nano-biosensors, and other advanced and unique contact and non-contact bio-imaging modalities.
Finally, this book examines the use of the above advanced bio-engineering and imaging techniques in studying: the quality of intact, osteoporotic, osteonecrotic,
VI Foreword (I)
osteo-arthritic, and healing bone and cartilage, and examines the role of these tech- nologies in assessing the vascularity of relevant hard and soft tissues along with var- ious scaffolding materials developed for musculoskeletal applications.
Harry K. Genant, M.D, FACR, FRCR (Honorary)
Emeritus Professor and Director, Osteoporosis and Arthritis Research Group, UCSF Chairman, WHO Task Force on Osteoporosis
Emeritus Chairman and Member, Board of Directors, Synarc, Inc.
Foreword (II) VII
Foreword (II)
Bone is a hard tissue and yet bone is constantly undergoing the most active dynamic processes of metabolism, which are the basic forces behind the rapidly changing in- ternal structure. Bone has a complex internal structure. On the gross anatomical level, it is comprised of a closely writhing, intermingled collection of hard columns, tra- beculations, tubes, fat and vascular components. On the histomorphometry level, it contains fine blood vessels, canals, minute pathways, different cells with widely di- vergent responsibilities. On the molecular level, it is even more complex: the differ- ent stages of growth and metabolism produce chemicals, metabolites, biochemical markers and binders, all of which take part in the colourful changes of bone.
The knowledge of bone as a complex structure was gathered over at least half a century: from gross anatomical histomorphometric studies to biochemical inves- tigations. In this long march to the understanding of the mysterious bone there occurred many breakthroughs, on which today’s knowledge is based. Radiologi- cal imaging was probably the first technique that allowed the external appearance and a summation of the internal structure to be revealed. With radiological im- ages surgeons could handle fractures logically and scientifically. Many decades of radio-imaging refinement and the application of computer interpretation advanced the simple technology to a detailed gross revelation. What followed were the spe- cial screening techniques with various radioisotopes and finally magnetic resonance technology, which illustrated on the images both soft tissues and bone activities. It is no surprise that the scientists who were responsible for the different stages of imaging earned the utmost honour of the Nobel Prize.
Bone imaging is still advancing. With the need to manage bone degradation as one ages, many generations of equipment to detect bone density have matured and are still undergoing refinement, since it is important to understand the gross values as well as the fine structures. The fine structures are gaining more and more signif- icance since bone metabolism is continuously being affected by mechanical forces.
The biomechanical influences directly and indirectly guide the degeneration and re- generation processes. Today the fine structures are revealed with imaging technology.
With this brief background, readers can appreciate this new volume, which covers current bioimaging techniques, focusing on the quality and fine structures of bone.
We all look forward to more contributions from this group of image experts, engi- neers, bioengineers and surgeons.
Prof. Ping-Chung Leung President
International Society of Orthopedic Research and Traumatology
VIII Foreword (III)
Foreword (III)
It was an honor for the International Chinese Hard Tissue Society to be a co-sponsor at the International Symposium on Advanced Bio-imaging Technologies in As- sessment of Quality of Bone and Scaffold Biomaterials, held at the Chinese Univer- sity of Hong Kong, Hong Kong, – October . The conference brought to- gether scientists worldwide to discuss cutting-edge technologies and the organizers were resourceful enough to convince speakers to contribute chapters to make this unique material available to the scientific community. The realization that one tech- nology cannot unravel the complexities that contribute to bone, cartilage, and frac- ture healing has led numerous investigators to employ various technologies; thus, the chapters in this book contain uses of micro-CT, nano-CT, digital radiography, ra- dioactive contrast medium, pQCT, backscattering electron microscopy, histochem- istry, immunochemistry, mineralization, collagen fiber orientation, polarized light microscopy, histology, finite element analysis, etc., mostly in combination, to eval- uate anti-osteoporotic drugs, bone and cartilage quality, fracture healing, and scaf- folding biomaterials. Many of these technologies are non-invasive, with high preci- sion or reproducibility, repeatability, and rapidity. They also reduce labor and do not require necropsy. Micro-CT was coupled with X-ray contrast agent to allow for the analyses of vasculature and articular cartilage. Nano-CT made it possible to quantify osteocytes, microcracks, and resorption lacunae. The development of the cutting- edge technologies and paragons was not for the sake of development or basic sci- ence alone, but were employed in translational research in the treatment of fracture healing, osteoporosis, osteoporotic fracture repair, regional bone adaptation, ovariec- tomy rat models, osteonecrosis, osteoarthritis, scoliosis, and evaluation of efficacy of various scaffold biomaterials. A few exciting examples include the in vivo micro-CT studies used to monitor change in trabecular structure in rats sequentially treated with bisphosphonate and parathyroid hormone, imaging the subtle erosive lesion in subchondral bone caused by inflammation processes in TNF-alpha transgenic mice and monitoring the progressive osteolytic response following administration and treatment of tumor cells in the tibial metaphyses of nude mice. In addition, se- ries with in vivo micro-CT studies of human early osteo-arthritis (OA) and guinea pig OA showed subchondral cancellous bone to be thicker and markedly plate-like, but weaker in mechanical properties, supporting the concept that the bone changes come before cartilage deterioration.
Each chapter contains new developments and findings; therefore, I strongly sug- gest this revolutionary book to all personnel and investigators working in the fields of musculoskeletal research and development.
Webster S.S. Jee, Ph.D
Professor of Neurobiology and Anatomy Chairman of the Board
International Chinese Hard Tissue Society
Foreword (IV) IX
Foreword (IV)
It is without exception that osteoporosis and other disorders and injury of bone and cartilage, as well as its repairing and regeneration, are omnipresent to relate with the relevant changes in its metabolism, microstructure, vasculature, quantity, and mechanical properties.
The evaluation of the quality and quantity of bone, cartilage, vasculature, and scaffold materials provide the basic elements for the diagnosis, prevention, and treat- ment of such diseases, which serves as the main evidence to evaluate the curative ef- fect and prognosis. By understanding the biological and biomechanical status of the musculoskeletal tissues, the diagnosis and scientific evaluations can be made after analysis of imaging characteristics and the status of turnover. This is the foundation for the prevention, management, and control of musculoskeletal diseases.
In recent years, both methods and equipment for evaluating structure, function, and mechanical properties of bone, cartilage, vasculature, and scaffold materials de- veloped for musculoskeletal applications have evolved rapidly. There is no doubt that, to a great extent, how to use such equipment in a logical and scientific way, by exerting the strength of different facilities, avoiding its shortcomings and the possible errors, as well as integrating analyses from the exam results, will determine the correctness and validity of the evaluation results. In this context, the knowledge and experience of the researchers involved are essential as well. It is likely that the same facilities in dif- ferent users’ hands might result in different applications, results, and interpretations.
It is true that in animal experiments, some invasive examinations still have great value for research and applications, where we could get the direct results of bone and cartilage microstructure, bone histomorphometry, cell and molecular biological analysis, and tissue and biomaterial interactions or integrations. But in clinical prac- tice, the patients obviously are more willing to receive the non-invasive exams. The non-invasive nature of recent developments in musculoskeletal imaging presented in this book contributes definitively to our clinical applications.
This book provides detailed introductions from different aspects on the work- ing principles and operating techniques of micro-CT, pQCT/QCT, MRI, and other imaging-related modalities. It also presents the related knowledge and experiences concerning in vitro and in vivo assessments for bone and cartilage on its microarchi- tecture, vasculature, fracture healing, and scaffolds for tissue engineering.
The contributors of this book are renowned experts and avant-garde researchers in their respective professions. It will serve as a unique reference book with both high academic and applied values for medical doctors, scientists, technologists, postgrad- uate students, and related persons. It may be expected that this book will bring inspi- ration and technological insights for our readers to enhance quality of research and develop new applications.
Kerong Dai
Academician, Chinese Academy of Engineering
Life Tenured Professor and Dean Ninth Hospital Medical School Shanghai Jiaotong University
X Preface
Preface
The purpose of this book is to provide a perspective on the current status of bio- imaging technologies developed for assessment of quality of musculoskeletal tissues, with emphasis on bone and cartilage, and evaluations of scaffold biomaterials de- veloped for enhancement of repair of musculoskeletal tissues; these include QCT, pQCT, micro-CT for animals and humans, nano-CT, MRI, ultrasound and other ad- vanced imaging modalities. The contents of this book are from the contributions pro- vided by the leading scientists and physicians in the related professions, who partici- pated in the International Symposium on Advanced Biotechnologies for Assessing Quality of Bone and Scaffold Biomaterials at the Chinese University of Hong Kong, Hong Kong SAR, China. Some other leading groups who were not able to attend this symposium have also contributed to this book. Their participation makes this book more comprehensive, with an even wider spectrum in musculoskeletal imag- ing technologies and their applications, from molecular imaging to visualization and simulation of human body with applications extended from musculoskeletal to car- diovascular research.
This book provides a unique platform for multidisciplinary research and may help to facilitate collaborations in development of science and technology, basic and applied biomedical education, as well as research and service among various professions, including biomedical engineering, biomaterials, and basic and clinical medicine. How to make full use of the advanced technologies is essential for further improvement of these biotechnologies. As such, this book is categorized into Part I, with emphasis on technologies, and Part II, the specific applications of those tech- nologies. The subject index is also summarized in this way; therefore, the readership covers medical doctors, clinical and material scientists, bioengineers, technologists, postgraduate students and related personnel.
As we are now in the middle of the Bone-Joint Decade (BJD), the editors hope that this book will contribute to BJD in a specific way, especially in diagnosis, pre- vention and treatment of aging-related disorders of musculoskeletal, cardiovascular and other relevant living tissues, organs, and systems.
Ling Qin, Ph.D
Professor and Director, Musculoskeletal Research Laboratory Department of Orthopaedics and Traumatology
The Chinese University of Hong Kong, Hong Kong SAR, China
List of Contents
Part I Perspectives of Advances in Musculoskeletal and Scaffold Biomaterial Imaging Technologies and Applications
I- Advances in Assessment of Quality of Bone and Orthopaedic Applications Perspectives on Advances in Bone Imaging for Osteoporosis
H. K. Genant, Ye-Bin Jiang . . . . Bone Structure and Biomechanical Analyses Using Imaging
and Simulation Technology
Edmund Y.S. Chao . . .
Imaging Technologies for Orthopaedic Visualization and Simulation
Pheng Ann Heng . . . .
In-Vivo Bone Mineral Density and Structures in Humans:
From Isotom Over Densiscan to Xtreme-CT
Maximilian A. Dambacher, Maurus Neff, Helmut R. Radspieler,
Peter Rüegsegger, Ling Qin . . .
Calibration of Micro-CT Data for Quantifying Bone Mineral and Biomaterial Density and Microarchitecture
Bruno Koller, Andres Laib . . .
Repositioning of the Region of Interest in the Radius of the Growing Child in Follow-up Measurements by pQCT
Thomas N. Hangartner, Dhruman Goradia, David F. Short . . .
Non-invasive Bone Quality Assessment Using Quantitative Ultrasound Imaging and Acoustic Parameters
Yi-Xian Qin, Wei Lin, Yi Xia, Erik Mittra, Clint Rubin, Ralph Müller . . .
XII List of Contents
I- Advances Microscopic Technologies and Applications
Cortical Bone Mineral Status Evaluated by pQCT, Quantitative Backscattered Electron Imaging and Polarized Light Microscopy
Yau-Ming Lai, Wing-Chi Chan . . .
High-Fidelity Histologic Three-Dimensional Analysis of Bone and Cartilage Russell Kerschmann . . .
Application of Laser Scanning Confocal Microscopy in Musculoskeletal Research
Kwong-Man Lee, Hiu-Yan Yeung . . .
Fiber-optic Nano-biosensors and Near-Field Scanning Optical Microscopy for Biological Imaging
Kin Fai Wu, Yuan Ting Zhang, Mary Miu Yee Waye . . .
Changes of Biological Function of Bone Cells and Effect of Anti-osteoporosis Agents on Bone Cells
Hong-Fu Wang, Weif-Ang Jin, Jian-Jun Gao, Hui Sheng . . .
Bone Histomorphometry in Various Metabolic Bone Diseases Studied by Bone Biopsy in China
Mei Zhu, Ming-cai Qiu . . .
Cell Traction Force Microscopy
James H.-C. Wang, Jeen-Shang Lin, Zhao-Chun Yang . . .
I- Advances in Vascular Research and Applications Contrast-Enhanced Micro-CT Imaging of Soft Tissues
Angela S.P. Lin, Ashley W. Palmer, Craig L. Duvall, Galen C. Robertson,
Megan E. Oest, Bina Rai, Marc E. Levenston, Robert E. Guldberg . . .
I- Advances in Scaffold Biomaterial Research and Applications Materials Selection and Scaffold Fabrication for Tissue Engineering in Orthopaedics
Min Wang . . .
Quantification of Porosity, Connectivity and Material Density of Calcium Phosphate Ceramic Implants Using Micro-Computed Tomography
Hiu-Yan Yeung, Ling Qin, Kwong-Man Lee, Kwok-Sui Leung,
Jack Chun-Yiu Cheng . . .
List of Contents XIII
Bone Densitometries in Assessing Bone Mineral and Structural Profiles in Patients with Adolescent Idiopathic Scoliosis
Jack Chun-Yiu Cheng, Vivian Wing-Yin Hung, Ling Qin, Xia Guo . . .
Application of Nano-CT and High-Resolution Micro-CT to Study Bone Quality and Ultrastructure, Scaffold Biomaterials and Vascular Networks
Phil L. Salmon, Alexander Y. Sasov . . .
Bio-imaging Technologies in Studying Bone-Biomaterial Interface:
Applications in Experimental Spinal Fusion Model
Chun Wai Chan, Jack Chun-Yiu Cheng, Hiu-Yan Yeung, Ling Qin . . .
Assessment of Bone, Cartilage, Tendon and Bone Cells by Confocal Laser Scanning Microscopy
Chris W. Jones, Kirk H.M. Yip, Jiake Xu, Ming-Hao Zheng . . .
Part II Specific Applications of Advances in Musculoskeletal and Scaffold Biomaterial Imaging Technologies
II- In Assessment of Osteoporosis and Treatment TEM Study of Bone and Scaffold Materials
Shu-Xin Qu, Xiong Lu, Yang Leng . . .
Material and Structural Basis of Bone Fragility:
A Rational Approach to Therapy
Ego Seeman . . .
Application of Micro-CT and MRI in Clinical
and Preclinical Studies of Osteoporosis and Related Disorders
Ye-Bin Jiang, Jon Jacobson, Harry K. Genant, Jenny Zhao . . .
CT-Based Microstructure Analysis for Assessment of Bone Fragility
Masako Ito . . .
Discrimination of Contributing Factors to Bone Fragility Using vQCT In Vivo
Margarita Meta, Ying Lu, Joyce H. Keyak, Thomas F. Lang . . .
Osteoporosis Research with the vivaCT
Jürg A. Gasser, Peter Ingold . . .
Mechanical Properties of Vertebral Trabeculae with Ageing Evaluated with Micro-CT
He Gong, Ming Zhang, Ling Qin . . .
MRI Evaluation of Osteoporosis
James Francis Griffith . . .
XIV List of Contents
Multiple Bio-imaging Modalities in Evaluation of Epimedium-Derived Phytoestrogenic Fraction for Prevention of Postmenopausal Osteoporosis
Ge Zhang, Ling Qin, Yin-Yu Shi . . .
Areal and Volumetric Bone Densitometry in Evaluation of Tai Chi Chuan Exercise for Prevention of Postmenopausal Osteoporosis
Pauline Po-Yee Lui, Ling Qin, Wing-Yin Choi, Kai-Ming Chan . . .
Enhancement of Osteoporotic Bone Using Injectable Hydroxyapatite in OVX Goats Evaluated by Multi-imaging Modalities
Wing-Hoi Cheung, Ling Qin, Kam-Fai Tam, Wing-Sum Siu, Kwok-Sui Leung . . .
II- In Assessment of Fracture Repair
Quality of Healing Compared Between Osteoporotic Fracture and Normal Traumatic Fracture
Ke-Rong Dai, Yong-Qiang Hao . . .
Monitoring Fracture Healing Using Digital Radiographies
Gang Li, Mark Murnaghan . . .
Fracture Callus Under Anti-resorptive Agent Treatment Evaluated by pQCT Yong-Ping Cao, Satoshi Mori, Tasuku Mashiba, Michael S. Westmore, Linda Ma .
II- In Assessment of Osteonecrosis
Volumetric Measurement of Osteonecrotic Femoral Head Using Computerized MRI and Prediction For Its Mechanical Properties
Zi-Rong Li, Zhen-Cai Shi . . .
Biomedical Engineering in Surgical Repair of Osteonecrosis:
the Role of Imaging Technology
Shi-Bi Lu, Jiang Peng, Ai-Yuan Wang, Ming-Xue Sun, Jie-Mo Tian, Li-Min Dong
Contrast-Enhanced MRI and Micro-CT Adopted for Evaluation of a Lipid- Lowering and Anticoagulant Herbal Epimedium-Derived Phytoestrogenic Extract for Prevention of Steroid-Associated Osteonecrosis
Ling Qin, Ge Zhang, Hui Sheng, James F. Griffth, Ka Wai Yeung, Kwok-Sui Leung
Nanomechanics of Bone and Bioactive Bone-Cement Interfaces
Guo-Xin Ni, William Wei-Jia Lu, Alfonso Hing-Wan Ngan, Keith Dip-Kei Luk . . .
II- In Assessment of Osteoarthritis
Subchondral Bone Microarchitecture Changes in Animal Models of Arthritis Susanne X. Wang . . .
List of Contents XV
Microarchitectural Adaptations of Primary Osteoarthrotic Subchondral Bone Ming Ding . . .
Ultrasonic Characterization of Dynamic Depth-Dependent Biomechanical Properties of Articular Cartilage
Yong-Ping Zheng, Qing Wang . . .
Mechanical Property of Trabecular Bone of the Femoral Heads from Osteoarthritis and Osteoporosis Patients
Cheng-Kung Cheng, Yu-Su Lai, Shih-Sheng Sun, Hsin-Wen Shen,
Chan-Tsung Yang, Hung-Wen Wei . . .
Index . . .
