TBME 60th Anniversary Special Issue

TBME 60th Anniversary Special Issue

IEEE Transactions on Biomedical Engineering (TBME) was one of the first journals devoted to biomedical engineering. To celebrate TBME’s 60th anniversary, we have published a special issue consisting of review articles from 20 leading groups in biomedical engineering research. These articles review state of the art and trends in biomedical imaging, neuroengineering, cardiovascular engineering, cellular and tissue engineering, biomedical sensors and instrumentation, biomedical signal processing, medical robotics, bioinformatics and computational biology. The special issue is witness to the development of the field of biomedical engineering, and also reflects the role that TBME has played in advancing the field of biomedical engineering over the past 60 years. TBME Volume 61, Issue 5

Biomedical Imaging

Magnetic Resonance Imaging at Ultrahigh Fields
Kamil Ugurbil, University of Minnesota
In the last two decades, ultrahigh magnetic fields (7 Tesla and above) have evolved to provide unprecedented gains for imaging human brain activity, anatomy and physiology, and have started to make inroads into the study of other organ systems. As extensive as they are, these gains still constitute a prelude to what is to come given the increasingly larger effort committed to this field of research and the continued rapid development of ever better instrumentation, as well as image acquisition, signal processing and analysis techniques. Read more

Small-Animal Whole-Body Photoacoustic Tomography: A Review
Jun Xia, Lihong Wang, Washington University in St. Louis2 Linhog Wang
With the wide use of small animals for biomedical studies, in vivo small-animal whole-body imaging plays an increasingly important role. Photoacoustic tomography (PAT) embodied for whole-body imaging has shown great potential for preclinical research. Capitalizing on the photoacoustic effect, which converts absorbed optical energy into acoustic energy, PAT provides high resolution images of optical absorption in both the optically ballistic and diffusive regimes. Anatomical, functional, and molecular PAT images are enabled by a rich variety of endogenous and exogenous optical contrasts. This paper reviews various photoacoustic whole-body imaging techniques and highlights selected studies done in the past decade. Read more

Electrical Tissue Property Imaging at Low Frequency Using MREIT
Jin KeunSeo, Eung Je Woo, Yonsei University, Kyung Hee University
The tomographic imaging of tissue’s electrical properties has been greatly improved by recent developments in magnetic resonance (MR) imaging techniques. In MREIT, we inject low-frequency currents into an imaging object and measure the induced magnetic flux density data using an MRI scanner. Solving a nonlinear inverse problem, we reconstruct cross-sectional images of the internal conductivity distribution. Read more

Breast Cancer Histopathology Image Analysis: A Review
Mitko Veta, Josien Pluim, Paul van Diest, Max Viergever, University Medical Center Utrecht, The Netherlands Pathology labs are currently undergoing a transformation towards a fully digital workflow, which includes digitization of histopathology slides. A relatively large percentage of the samples that are analyzed by pathologists are from breast cancer patients, since this disease is the most prevalent form of cancer among women. One of the main benefits of digital slides compared to conventional glass slides is that they enable the use of quantitative automatic image analysis methods. In this paper, we give an overview of image analysis methods that have been proposed for breast cancer histopathology images. Read more


Retinal Prosthesis
James D. Weiland & Mark S. Humayun, University of Southern California
Retinal prostheses have been translated from the laboratory to the clinic over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration that patients use in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This review summarizes the recent clinical trials and highlights technology breakthroughs that will contribute to next generation of retinal prostheses. Read more

Brain-Computer Interfaces Using Sensorimotor Rhythms: Current State and Future Perspectives
Han Yuan, Bin He, Laureate Institute for Brain Research & University of Minnesota binhe-th
Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer using brain-computer interfaces (BCIs). BCI systems extract specific features of brain activity and translate them into control signals that drive an output. Recently, a category of BCIs that are built on the rhythmic activity recorded over the sensorimotor cortex, i.e. the sensorimotor rhythm (SMR), has attracted considerable attention among the BCIs that use noninvasive neural recordings, e.g. electroencephalography (EEG), and have demonstrated the capability of multi-dimensional prosthesis control. This article reviews the current state and future perspectives of SMR-based BCI and its clinical applications, in particular focusing on the EEG SMR. Read more

Visual and Auditory Brain-Computer Interfaces
Shangkai Gao, Yijun Wang, Xiaorong Gao, Bo Hong, Tsinghua University & University of California San Diego
Over the past several decades, electroencephalogram(EEG)-based brain-computer interfaces (BCIs) have attracted attention from researchers in the field of neuroscience, neural engineering, and clinical rehabilitation. Recently, visual and auditory BCI systems have become popular because of their high communication speeds, little user training, and low user variation. In this paper, we review the current state and future challenges of visual and auditory BCI systems. A new taxonomy based on the multiple access methods used in telecommunication systems is described. Also, the challenges of translating current technology into real-life practices and outline potential avenues to address them are discussed. Read more

The Past, Present, and Future of Real-Time Control in Cellular Electrophysiology
Jennifer Bauer, Katherine Lambert, John White, University of Utah
For over 60 years, real-time control has been important for the study of excitable cells. Two such control-based technologies are reviewed here. Voltage-clamp methods revolutionized the study of excitable cells. In these techniques, membrane potential is controlled, allowing one to parameterize a powerful class of models that describe the voltage-current relationship of cell membranes. Dynamic-clamp methods allow the addition of new, ‘virtual’ membrane mechanisms to living cells. Dynamic clamp allows researchers unprecedented ways of testing computationally based hypotheses in biological preparations. Future improvements and uses of control-based technologies are also discussed. Read more

Cardiovascular Engineering

A Brief History of Tissue Models for Cardiac Electrophysiology
Craig Henriquez, Duke University9 Henriquez small
The first biophysically based cardiac tissue model, combining a description of the cell-to-cell connections with a realistic representation of the membrane current fluxes, was developed nearly 45 years ago. In the decades that followed, these models were refined and advanced with contributions from the fields of clinical cardiology, cell biology, physiology, computer science and biomedical engineering. Descriptions have evolved from a single fiber of a few cells to full three-dimensional representations of the whole heart. These models have been used to investigate the role of gap junctions, fiber orientation, ion-channel kinetics, non-uniform ion channel distribution, and geometry on the genesis and maintenance of arrhythmias like ventricular tachycardia and atrial fibrillation.  Read more

A Shocking Past: A Walk Through Generations of Defibrillation Development
Sarah Gutbrod, Igor Efimov, Washington University in Saint Louis
Defibrillation is one of the most successful applications and well-known triumphs of biomedical engineering. Yet the historical road to its clinical success and the innovative adaptation to an implantable device are marred with unexpected turns, political and personal setbacks, and public and scientific condemnation at each new idea. Driven by dedicated scientists and creative applications of new technologies, from electrocardiography to mapping and computational simulations, the field of defibrillation persevered and evolved to the life-saving tool it is today. The history of defibrillation is also marked by the plasticity of the theory and practice of electrotherapy, which are still evolving. Read more

Cellular and Tissue Engineering

Hydrogels as Carriers for Stem Cell Transplantation
Melissa Alvarado-Velez, Balakrishna Pai, Ravi Bellamkonda, Georgia Institute of Technology & Emory University
Stem cell transplantation is a promising therapy for several degenerative conditions. However, a number of limitations such as low cell survival, uncontrolled and/or low differentiation, induction of host immune response, and the risk of teratoma formation make this approach challenging. In this review, we explore the utility of hydrogels as carriers for stem cell delivery and their potential to overcome some of the current limitations in stem cell therapy. We focus on in situ gelling hydrogels, and also discuss other strategies to modulate the immune response to promote controlled stem cell differentiation. Immunomodulatory hydrogels and gels designed to promote cell survival and integration into the host site will likely have a significant impact on enhancing the efficacy of stem cell transplantation as a therapy for debilitating degenerative diseases. Read more

Strategies for Whole Lung Tissue Engineering
Elizabeth Calle, Mahboobe Ghaedi, Sumati Sundaram, Amogh Sivarapatna, Michelle Tseng, Laura Niklason
Yale UniversityStrategies for Whole Lung Tissue Engineering

Whole organ engineering has progressed rapidly in recent years. This is in large part due to the increased availability and use of decellularized whole lung organ scaffolds. This strategy is particularly advantageous for the lung, as it possesses a complex branching structure that is critical to its function of gas exchange. In addition to an appropriate scaffold that is sterile and hospitable to cell growth, epithelial, endothelial, and mesenchymal cells are required, as well as a bioreactor system in which to cultivate the organ. Here, we describe the successes and challenges in each of these areas of whole lung engineering.  Read more

Recent Advances in Thermal Treatment Techniques and Thermally Induced Immune Responses Against Cancer
Jingfeng Bai, Ping Liu, Lisa X Xu,Shanghai Jiao Tong University13 Lisa Xu small
Thermal ablation techniques present promising approaches to tumor treatment, and it has been recognized lately the possible of whole body immune response through thermally induced depletion of immune suppression cells and in situ release of tumor specific antigens. In this paper, recent developments of thermal ablation techniques are reviewed and compared with the emphasis on thermal energy delivery methods, thermally induced immunological responses in depth. It is suggested that the synergy of local thermal ablation and thermally induced whole body immune response could be a promising direction for effective cancer therapy in the near future, especially for highly metastatic tumor. Read more

Biomedical Sensors and Instrumentation

Toward Integrated Molecular Diagnostic System (iMDx): Principles and Applications
Seung-min Park, Andrew Sabour, Jun Ho Son, Sang Hun Lee, Luke Lee
Stanford University & University of California, Berkeley14 60th Luke Lee

Portable microfluidic devices (coined iMDx) encompassing entire lab equipment and experimental procedures on a self-automated micro-scale platform have emerged as a hot topic in the field of medical research. This review walks through each element critical in an integrated diagnostic platform, outlining their developmental history, various publications and their respective pros/cons, adaptations to fit the diagnostic function desired, and possible ways of integration in the future. A final discussion on integrated devices currently used in clinical fields presents both a foundation to experiment from and the possibility for greater growth in integrated diagnostics. Read more

Integrated Circuits and Electrode Interfaces for Non-Invasive Physiological Monitoring
Sohmyung Ha, Chul Kim, Mike Chi, Abraham Akinin, Christoph Maier, Akinori Ueno, Gert Cauwenberghs
University of California San Diego, Cognionics Inc., and Tokyo Denki University
Throughout the history of biomedical instrumentation, non-invasive techniques for physiological monitoring have been indispensable to health care practitioners for rapid, reliable, and minimally obtrusive diagnosis, whether during regular check-ups in the doctor’s office or during critical care delivery in the emergency room. Advances in microelectronic and optical integrated circuits and electrode interfaces offer technological foundations for transformative applications of continuous physiological sensing, improving efficiency and lowering cost of personalized care by pervasive and mobile monitoring of health and fitness anytime and anywhere. This review offers a survey of decades of progress in technological advances and an outlook on emerging directions of current research, with examples of practical dry-contact and non-contact cardiac, respiratory, muscle and brain monitoring systems and their clinical applications. Read more

Unobtrusive Sensing and Wearable Devices for Health Informatics
Yali Zheng, Xiaorong Ding, Carmen Poon, Benny Lo, Heye Zhang, Xiaolin Zhou, Guang-Zhong Yang, Ni Zhao, Yuanting Zhang, The Chinese University of Hong Kong, Chinese Academy of Sciences, Imperial College Londonezgif-save-6
The aging population, prevalence of chronic diseases, and outbreaks of infectious diseases are some of the major challenges of the present-day society. To address these unmet healthcare needs, especially for the early prediction and treatment of major diseases, health informatics which deals with the acquisition, transmission, processing, storage, retrieval, and use of health information has emerged as an active area of interdisciplinary research. In particular, acquisition of health-related information by unobtrusive sensing and wearable technologies is considered as a cornerstone in health informatics. Sensors can be weaved or integrated into clothing, accessories and the living environment. Read more

Biomedical Signal Processing

A Review of Multitaper Spectral Analysis
Behtash Babadi, Emery Brown, University of Maryland, College Park & Massachusetts Institute of TechnologyPrint
Spectral estimation is a widely used technique in many applications ranging from radar and seismic data analysis to electroencephalography (EEG) and speech processing. Among the techniques used for estimating the spectral representation of a system based on finite observations, multitaper spectral estimation is arguably the first non-parametric method to address simultaneously in an ‘optimal’ fashion the issues of bias and variance. But is not as widely used as it possibly could be. We give a brief overview of the standard non-parametric spectral estimation theory and the multitaper spectral estimation, and give two examples from EEG analyses of anesthesia and sleep to illustrate the ease with which the latter approach can be applied and the types of insights it brings. Read more

Medical Robotics

From Passive Tool Holders to Microsurgeons: Safer, Smaller, Smarter Surgical Robots
Christos Bergeles, Guang-Zhong Yang, Imperial College London18 G Yang
Within only a few decades, the field of surgical robotics has evolved into a dynamic and rapidly growing research area with increasing clinical uptake worldwide. Surgical robots are now involved in an increasing number of procedures, demonstrating their practical clinical potential whilst propelling further advances in surgical innovations. This paper provides an overview of the significant achievements in surgical robotics and identifies the current trends and future research directions of the field in making surgical robots safer, smaller, and smarter. Read more

Bioinformatics and Computational Biology

Advancing Our Understanding of the Glucose System via Modeling: A Perspective
Claudio Cobelli, Chiara Dalla Man, Morten Pedersen; Alessandra Bertoldo, Gianna Toffolo, University of Padova19 60th Cobelli resized_updated
The glucose story begins with Claude Bernard’s discovery of glycogen and milieu interieur, continued with Banting’s and Best’s discovery of insulin and with Rudolf Schoenheimer’s paradigm of dynamic body constituents. Tracers and compartmental models allowed moving to the first quantitative pictures of the system, first, using analog and, later, digital computers. The glucose regulation system has stimulated important developments in terms of modeling methodology. The historical development of three classes of multi-scale models, models to measure (minimal – coarse grained), models to simulate (maximal – fine grained) and models to control, and their role in advancing the understanding of the pathophysiology of diabetes are reviewed with an eye to the future. Read more

Dissecting Heart Failure Through the Multiscale Approach of Systems Medicine
Linda Pattini, Roberto Sassi, Sergio Cerutti, Politecnico di Milano and Università degli Studi di MilanoDissecting Heart Failure Through the Multiscale Approach of Systems Medicine
Heart Failure is a complex syndrome that can really benefit from the systems medicine approach where information at different scales is exploited to comprehend pathologic mechanisms from the cellular program to the phenotype assessed at the organ and system level. In this review, evidences concerning current understanding of Heart Failure, surveying different types of experimental data, are reported, to underline how functional genomics and systems biology perspective, fostered by the combination of biotechnologies and information engineering, may provide a more complete picture of pathophysiological mechanisms toward personalized medicine. Read more



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