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  • Articles  (300)
  • Annual Reviews  (300)
  • Springer Science + Business Media
  • 2005-2009  (89)
  • 2000-2004  (211)
  • 1980-1984
  • Technology  (300)
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  • 1
    Electronic Resource
    Electronic Resource
    BIOPHYSICAL INJURY MECHANISMS IN ELECTRICAL SHOCK TRAUMA (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 477-509 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.477
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  • 2
    Electronic Resource
    Electronic Resource
    NEUROENGINEERING MODELS OF BRAIN DISEASE (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 577-606 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The techniques of computational simulation have begun to be applied to modeling neurological disease and mental illness. Such neuroengineering models provide a conceptual bridge between molecular/cellular pathology and cognitive performance. We consider models of Alzheimer's disease, Parkinson's disease, and schizophrenia. Each of these diseases involves a disorder of neuromodulation coupled with underlying neuronal pathology. Parallels arising between these models suggests that a common set of computational mechanisms may account for functional loss across a spectrum of brain diseases. In particular, we focus on attractor-based network dynamics and how they arise from neural architectures, on mechanisms for linking sequences of attractor states and their role in cognition, and on the role of neuromodulation in controlling these processes. These studies suggest new approaches to understanding the forebrain circuits underlying cognition, and point toward a new tool for dissecting the pathophysiology of brain disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.577
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  • 3
    Electronic Resource
    Electronic Resource
    CARTILAGE TISSUE REMODELING IN RESPONSE TO MECHANICAL FORCES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 691-713 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Recent studies suggest that there are multiple regulatory pathways by which chondrocytes in articular cartilage sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation, post-translational modifications, and cell-mediated extracellular assembly and degradation of the tissue matrix. This review focuses on the effects of mechanical loading on cartilage and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair of this tissue. The effects of compression and tissue shear deformation are compared, and approaches to the study of mechanical regulation of gene expression are described. Of particular interest regarding dense connective tissues, recent experiments have shown that mechanotransduction is critically important in vivo in the cell-mediated feedback between physical stimuli, the molecular structure of newly synthesized matrix molecules, and the resulting macroscopic biomechanical properties of the tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.691
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  • 4
    Electronic Resource
    Electronic Resource
    BIOMECHANICS OF CARDIOVASCULAR DEVELOPMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 1-25 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract It long has been known that mechanical forces play a role in the development of the cardiovascular system, but only recently have biomechanical engineers begun to explore this field. This paper reviews some of this work. First, an overview of the relevant biology is discussed. Next, a mechanical theory is presented that can be used to model developmental processes. The theory includes the effects of finite volumetric growth and active contractile forces. Finally, applications of this and other theories to problems of cardiovascular development are discussed, and some future directions are suggested. The intent is to stimulate further interest among engineers in this important area of research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.1
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  • 5
    Electronic Resource
    Electronic Resource
    MICROENGINEERING OF CELLULAR INTERACTIONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 227-256 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation-and adaptation-of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.227
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  • 6
    Electronic Resource
    Electronic Resource
    THREE-DIMENSIONAL ULTRASOUND IMAGING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 457-475 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Two-dimensional viewing of three-dimensional anatomy by conventional ultrasound limits our ability to quantify and visualize a number of diseases and is partly responsible for the reported variability in diagnosis. Over the past two decades, many investigators have addressed this limitation by developing three-dimensional imaging techniques, including three-dimensional ultrasound imaging. In this paper we describe the development of a number of three-dimensional ultrasound imaging systems that make use of B mode, color Doppler, and power Doppler. In these systems, the conventional ultrasound transducer is scanned mechanically or by a freehand technique. The ultrasound images are digitized and then reconstructed into a three-dimensional volume, which can be viewed and manipulated interactively by the diagnostician with a variety of image-rendering techniques. These developments as well as future trends are discussed with regard to their applications and limitations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.457
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  • 7
    Electronic Resource
    Electronic Resource
    MICRODEVICES IN MEDICINE1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 551-576 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The application of microelectromechanical systems (MEMS) to medicine is described. Three types of biomedical devices are considered, including diagnostic microsystems, surgical microsystems, and therapeutic microsystems. The opportunities of MEMS miniaturization in these emerging disciplines are considered, with emphasis placed on the importance of the technology in providing a better outcome for the patient and a lower overall health care cost. Several case examples in each of these areas are described. Key aspects of MEMS technology as it is applied to these three areas are described, along with some of the fabrication challenges.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.551
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  • 8
    Electronic Resource
    Electronic Resource
    MAGNETIC RESONANCE STUDIES OF BRAIN FUNCTION AND NEUROCHEMISTRY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 633-660 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.633
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  • 9
    Electronic Resource
    Electronic Resource
    THOMAS MCMAHON: A Dedication in Memoriam (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. xv 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Thomas A. McMahon (1943-1999) was a pioneer in the field of biomechanics. He made primary contributions to our understanding of terrestrial locomotion, allometry and scaling, cardiac assist devices, orthopedic biomechanics, and a number of other areas. His work was frequently characterized by the use of simple mathematical models to explain seemingly complex phenomena. He also validated these models through creative experimentation. McMahon was a successful inventor and also published three well-received novels. He was raised in Lexington, Massachussetts, attended Cornell University as an undergraduate, and earned a PhD at MIT. From 1970 until his death, he was a member of the faculty of Harvard University, where he taught biomedical engineering. He is fondly remembered as a warm and gentle colleague and an exemplary mentor to his students.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.0
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  • 10
    Electronic Resource
    Electronic Resource
    CARDIAC ENERGY METABOLISM: Models of Cellular Respiration (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 57-81 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The heart requires a large amount of energy to sustain both ionic homeostasis and contraction. Under normal conditions, adenosine triphosphate (ATP) production meets this demand. Hence, there is a complex regulatory system that adjusts energy production to meet this demand. However, the mechanisms for this control are a topic of active debate. Energy metabolism can be divided into three main stages: substrate delivery to the tricarboxylic acid (TCA) cycle, the TCA cycle, and oxidative phosphorylation. Each of these processes has multiple control points and exerts control over the other stages. This review discusses the basic stages of energy metabolism, mechanisms of control, and the mathematical and computational models that have been used to study these mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.57
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  • 11
    Electronic Resource
    Electronic Resource
    NEW DNA SEQUENCING METHODS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 195-223 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The Human Genome Project and other major genomic sequencing projects have pushed the development of sequencing technology. In the past six years alone, instrument throughput has increased 15-fold. New technologies are now on the horizon that could yield massive increases in our capacity for de novo DNA sequencing. This review presents a summary of state-of-the-art technologies for genomic sequencing and describes technologies that may be candidates for the next generation of DNA sequencing instruments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.195
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  • 12
    Electronic Resource
    Electronic Resource
    COMPUTER MODELING AND SIMULATION OF HUMAN MOVEMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 245-273 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Recent interest in using modeling and simulation to study movement is driven by the belief that this approach can provide insight into how the nervous system and muscles interact to produce coordinated motion of the body parts. With the computational resources available today, large-scale models of the body can be used to produce realistic simulations of movement that are an order of magnitude more complex than those produced just 10 years ago. This chapter reviews how the structure of the neuromusculoskeletal system is commonly represented in a multijoint model of movement, how modeling may be combined with optimization theory to simulate the dynamics of a motor task, and how model output can be analyzed to describe and explain muscle function. Some results obtained from simulations of jumping, pedaling, and walking are also reviewed to illustrate the approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.245
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  • 13
    Electronic Resource
    Electronic Resource
    SOFT LITHOGRAPHY IN BIOLOGY AND BIOCHEMISTRY (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 335-373 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (〉=50 mum), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.335
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  • 14
    Electronic Resource
    Electronic Resource
    PEPTIDE AGGREGATION IN NEURODEGENERATIVE DISEASE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 155-174 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In the not-so-distant past, insoluble aggregated protein was considered as uninteresting and bothersome as yesterday's trash. More recently, protein aggregates have enjoyed considerable scientific interest, as it has become clear that these aggregates play key roles in many diseases. In this review, we focus attention on three polypeptides: beta-amyloid, prion, and huntingtin, which are linked to three feared neurodegenerative diseases: Alzheimer's, "mad cow," and Huntington's disease, respectively. These proteins lack any significant primary sequence homology, yet their aggregates possess very similar features, specifically, high beta-sheet content, fibrillar morphology, relative insolubility, and protease resistance. Because the aggregates are noncrystalline, secrets of their structure at nanometer resolution are only slowly yielding to X-ray diffraction, solid-state NMR, and other techniques. Besides structure, the aggregates may possess similar pathways of assembly. Two alternative assembly pathways have been proposed: the nucleation-elongation and the template-assisted mode. These two modes may be complementary, not mutually exclusive. Strategies for interfering with aggregation, which may provide novel therapeutic approaches, are under development. The structural similarities between protein aggregates of dissimilar origin suggest that therapeutic strategies successful against one disease may have broad utility in others.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092801.094202
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  • 15
    Electronic Resource
    Electronic Resource
    BIOMECHANICAL DYNAMICS OF THE HEART WITH MRI (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 321-347 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Magnetic resonance imaging (MRI) provides a noninvasive way to evaluate the biomechanical dynamics of the heart. MRI can provide spatially registered tomographic images of the heart in different phases of the cardiac cycle, which can be used to assess global cardiac function and regional endocardial surface motion. In addition, MRI can provide detailed information on the patterns of motion within the heart wall, permitting calculation of the evolution of regional strain and related motion variables within the wall. These show consistent patterns of spatial and temporal variation in normal subjects, which are affected by alterations of function due to disease. Although still an evolving technique, MRI shows promise as a new method for research and clinical evaluation of cardiac dynamics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.020702.153434
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  • 16
    Electronic Resource
    Electronic Resource
    STRUCTURAL, FUNCTIONAL, AND MOLECULAR MR IMAGING OF THE MICROVASCULATURE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 29-56 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121606
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  • 17
    Electronic Resource
    Electronic Resource
    TEMPORAL DYNAMICS OF BRAIN ANATOMY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 119-145 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The brain changes profoundly in structure and function during development and as a result of diseases such as the dementias, schizophrenia, multiple sclerosis, and tumor growth. Strategies to measure, map, and visualize these brain changes are of immense value in basic and clinical neuroscience. Algorithms that map brain change with sufficient spatial and temporal sensitivity can also assess drugs that aim to decelerate or arrest these changes. In neuroscience studies, these tools can reveal subtle brain changes in adolescence and old age and link these changes with measurable differences in brain function and cognition. Early detection of brain change in patients at risk for dementia; tumor recurrence; or relapsing-remitting conditions, such as multiple sclerosis, is also vital for optimizing therapy. We review a variety of mathematical and computational approaches to detect structural brain change with unprecedented sensitivity, both spatially and temporally. The resulting four-dimensional (4-D) maps of brain anatomy are warehoused in population-based brain atlases. Here, statistical tools compare brain changes across subjects and across populations, adjusting for complex differences in brain structure. Brain changes in an individual can be compared with a normative database comprised of subjects matched for age, gender, and other demographic factors. These dynamic brain maps offer key biological markers for understanding disease progression and testing therapeutic response. The early detection of disease-related brain changes is also critical for possible pre-emptive intervention before the ravages of disease have set in.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121611
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  • 18
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    COCHLEAR IMPLANTS: Some Likely Next Steps* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 207-249 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The history of cochlear implants is marked by large improvements in performance, especially over the past two decades and especially due to the development of ever-better processing strategies. Although the progress to date has been substantial, present devices still do not restore normal speech reception, even for top performers and particularly for listening to speech in competition with noise or other talkers. In addition, a wide range of outcomes persists, with some patients receiving little benefit using the same devices that support high levels of speech reception for others. The purpose of this review is to describe some likely possibilities for further improvement, including (a) combined electric and acoustic stimulation of the auditory system for patients with significant residual hearing, (b) use of bilateral implants, (c) a closer replication with implants of the processing steps in the normal cochlea, and (d) applications of knowledge about factors that are correlated with outcomes to help patients presently at the low end of the performance scale.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121645
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  • 19
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    NEURAL TISSUE ENGINEERING: Strategies for Repair and Regeneration (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 293-347 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120731
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  • 20
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    ADVANCES IN QUANTITATIVE ELECTROENCEPHALOGRAM ANALYSIS METHODS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 453-495 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121601
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  • 21
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    FLUID MECHANICS OF HEART VALVES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 331-362 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140111
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  • 22
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    BIOENGINEERING MODELS OF CELL SIGNALING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 31-53 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.31
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  • 23
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    ELECTROPHYSIOLOGICAL MODELING OF CARDIAC VENTRICULAR FUNCTION: From Cell to Organ (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 119-155 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Three topics of importance to modeling the integrative function of the heart are reviewed. The first is modeling of the ventricular myocyte. Emphasis is placed on excitation-contraction coupling and intracellular Ca2+ handling, and the interpretation of experimental data regarding interval-force relationships. Second, data on use of diffusion tensor magnetic resonance (DTMR) imaging for measuring the anatomical structure of the cardiac ventricles are presented. A method for the semi-automated reconstruction of the ventricles using a combination of gradient recalled acquisition in the steady state (GRASS) and DTMR images is described. Third, we describe how these anatomically and biophysically based models of the cardiac ventricles can be implemented on parallel computers.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.119
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    MICROFABRICATED MICRONEEDLES FOR GENE AND DRUG DELIVERY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 289-313 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract By incorporating techniques adapted from the microelectronics industry, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve existing biological-laboratory and medical devices and to enable novel devices for gene and drug delivery. Dense arrays of microneedles have been used to deliver DNA into cells. Many cells are treated at once, which is much more efficient than current microinjection techniques. Microneedles have also been used to deliver drugs into local regions of tissue. Microfabricated neural probes have delivered drugs into neural tissue while simultaneously stimulating and recording neuronal activity, and microneedles have been inserted into arterial vessel walls to deliver antirestenosis drugs. Finally, microhypodermic needles and microneedles for transdermal drug delivery have been developed to reduce needle insertion pain and tissue trauma and to provide controlled delivery across the skin. These needles have been shown to be robust enough to penetrate skin and dramatically increase skin permeability to macromolecules.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.289
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    TWO-PHOTON EXCITATION FLUORESCENCE MICROSCOPY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 399-429 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Two-photon fluorescence microscopy is one of the most important recent inventions in biological imaging. This technology enables noninvasive study of biological specimens in three dimensions with submicrometer resolution. Two-photon excitation of fluorophores results from the simultaneous absorption of two photons. This excitation process has a number of unique advantages, such as reduced specimen photodamage and enhanced penetration depth. It also produces higher-contrast images and is a novel method to trigger localized photochemical reactions. Two-photon microscopy continues to find an increasing number of applications in biology and medicine.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.399
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    IMAGING THREE-DIMENSIONAL CARDIAC FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 431-456 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The three-dimensional (3-D) nature of myocardial deformations is dependent on ventricular geometry, muscle fiber architecture, wall stresses, and myocardial-material properties. The imaging modalities of X-ray angiography, echocardiography, computed tomography, and magnetic resonance (MR) imaging (MRI) are described in the context of visualizing and quantifying cardiac mechanical function. The quantification of ventricular anatomy and cavity volumes is then reviewed, and surface reconstructions in three dimensions are demonstrated. The imaging of myocardial wall motion is discussed, with an emphasis on current MRI and tissue Doppler imaging techniques and their potential clinical applications. Calculation of 3-D regional strains from motion maps is reviewed and illustrated with clinical MRI tagging results. We conclude by presenting a promising technique to assess myocardial-fiber architecture, and we outline its potential applications, in conjunction with quantification of anatomy and regional strains, for the determination of myocardial stress and work distributions. The quantification of multiple components of 3-D cardiac function has potential for both fundamental-science and clinical applications.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.431
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    WAVELETS IN TEMPORAL AND SPATIAL PROCESSING OF BIOMEDICAL IMAGES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 511-550 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract We review some of the most recent advances in the area of wavelet applications in medical imaging. We first review key concepts in the processing of medical images with wavelet transforms and multiscale analysis, including time-frequency tiling, overcomplete representations, higher dimensional bases, symmetry, boundary effects, translational invariance, orientation selectivity, and best-basis selection. We next describe some applications in magnetic resonance imaging, including activation detection and denoising of functional magnetic resonance imaging and encoding schemes. We then present an overview in the area of ultrasound, including computational anatomy with three-dimensional cardiac ultrasound. Next, wavelets in tomography are reviewed, including their relationship to the radon transform and applications in position emission tomography imaging. Finally, wavelet applications in digital mammography are reviewed, including computer-assisted diagnostic systems that support the detection and classification of small masses and methods of contrast enhancement.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.511
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    EXTRACORPOREAL TISSUE ENGINEERED LIVER-ASSIST DEVICES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 607-632 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The treatment of acute liver failure has evolved to the current concept of hybrid bioartificial liver (BAL) support, because wholly artificial systems have not proved efficacious. BAL devices are still in their infancy. The properties that these devices must possess are unclear because of our lack of understanding of the pathophysiology of liver failure. The considerations that attend the development of BAL devices are herein reviewed. These considerations include choice of cellular component, choice of membrane component, and choice of BAL system configuration. Mass transfer efficiency plays a role in the design of BAL devices, but the complexity of the systems renders detailed mass transfer analysis difficult. BAL devices based on hollow-fiber bioreactors currently show the most promise, and available results are reviewed herein. BAL treatment is designed to support patients with acute liver failure until an organ becomes available for transplantation. The results obtained to date, in this relatively young field, point to a bright future. The risks of using xenogeneic treatments have yet to be defined. Finally, the experience gained from the past and current BAL systems can be used as a basis for improvement of future BAL technology.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.607
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    INTERVENTIONAL AND INTRAOPERATIVE MAGNETIC RESONANCE IMAGING1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 661-690 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The goal of the Image Guided Therapy Program, as the name implies, is to develop the use of imaging to guide minimally invasive therapy. The program combines interventional and intraoperative magnetic resonance imaging (MRI) with high-performance computing and novel therapeutic devices. In clinical practice the multidisciplinary program provides for the investigation of a wide range of interventional and surgical procedures. The Signa SP 0.5 T superconducting MRI system (GE Medical Systems, Milwaukee, WI) has a 56-cm-wide vertical gap, allowing access to the patient and permitting the execution of interactive MRI-guided procedures. This system is integrated with an optical tracking system and utilizes flexible surface coils and MRI-compatible displays to facilitate procedures. Images are obtained with routine pulse sequences. Nearly real-time imaging, with fast gradient-recalled echo sequences, may be acquired at a rate of one image every 1.5 s with interactive image plane selection. Since 1994, more than 800 of these procedures, including various percutaneous procedures and open surgeries, have been successfully performed at Brigham and Women's Hospital (Boston, MA).
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.661
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    IN VIVO NEAR-INFRARED SPECTROSCOPY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 715-754 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Interrogation of tissue with light offers the potential for noninvasive chemical measurement, and penetration with near-infrared wavelengths (750-1000 nm) is greater than with visible light. Specific absorption by clinically relevant compounds such as oxy- and deoxyhemoglobin and the intracellular respiratory enzyme cytochrome oxidase enable in vivo measurement of these to be performed safely and conveniently. This is the basis of in vivo near-infrared spectroscopy (ivNIRS). Multiple scattering of the interrogating beam by tissues leads to an optical path that is considerably longer than the simple physical pathlength and this complicates the analysis. Modeling of photon propagation through tissues with, for example, finite element and Monte Carlo methods, is assisting in improving the ivNIRS methodology. Instrumentation has advanced from simple continuous wave approaches, through time-resolved methods based on either time-domain or frequency-domain approaches, to spatially resolved measurement based on diffuse reflectance. Initial clinical applications were for monitoring the brain in the neonate and fetus and muscle in adults. Currently, use in adults and children for neurological assessments are of growing interest.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.715
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    THE PROCESS AND DEVELOPMENT OF IMAGE-GUIDED PROCEDURES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 83-108 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Medical imaging has been used primarily for diagnosis. In the past 15 years there has been an emergence of the use of images for the guidance of therapy. This process requires three-dimensional localization devices, the ability to register medical images to physical space, and the ability to display position and trajectory on those images. This paper examines the development and state of the art in those processes.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.83
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    CAN WE MODEL NITRIC OXIDE BIOTRANSPORT? A SURVEY OF MATHEMATICAL MODELS FOR A SIMPLE DIATOMIC MOLECULE WITH SURPRISINGLY COMPLEX BIOLOGICAL ACTIVITIES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 109-143 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Nitric oxide (NO) is a remarkable free radical gas whose presence in biological systems and whose astonishing breadth of physiological and pathophysiological activities have only recently been recognized. Mathematical models for NO biotransport, just beginning to emerge in the literature, are examined in this review. Some puzzling and paradoxical properties of NO may be understood by modeling proposed mechanisms with known parameters. For example, it is not obvious how NO can survive strong scavenging by hemoglobin and still be a potent vasodilator. Recent models do not completely explain how tissue NO can reach effective levels in the vascular wall, and they point toward mechanisms that need further investigation. Models help to make sense of extremely low partial pressures of NO exhaled from the lung and may provide diagnostic information. The role of NO as a gaseous neurotransmitter is also being understood through modeling. Studies on the effects of NO on O2 transport and metabolism, also reviewed, suggest that previous mathematical models of transport of O2 to tissue need to be revised, taking the biological activity of NO into account.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.109
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    VASCULAR TISSUE ENGINEERING (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 225-243 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The development of a tissue-engineered blood vessel substitute has motivated much of the research in the area of cardiovascular tissue engineering over the past 20 years. Several methodologies have emerged for constructing blood vessel replacements with biological functionality. These include cell-seeded collagen gels, cell-seeded biodegradable synthetic polymer scaffolds, cell self-assembly, and acellular techniques. This review details the most recent developments, with a focus on core technologies and construct development. Specific examples are discussed to illustrate both the benefits and shortcomings of each methodology, as well as to underline common themes. Finally, a brief perspective on challenges for the future is presented.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.225
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    BIOMECHANICS OF TRABECULAR BONE (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 307-333 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Trabecular bone is a complex material with substantial heterogeneity. Its elastic and strength properties vary widely across anatomic sites, and with aging and disease. Although these properties depend very much on density, the role of architecture and tissue material properties remain uncertain. It is interesting that the strains at which the bone fails are almost independent of density. Current work addresses the underlying structure-function relations for such behavior, as well as more complex mechanical behavior, such as multiaxial loading, time-dependent failure, and damage accumulation. A unique tool for studying such behavior is the microstructural class of finite element models, particularly the "high-resolution" models. It is expected that with continued progress in this field, substantial insight will be gained into such important problems as osteoporosis, bone fracture, bone remodeling, and design/analysis of bone-implant systems. This article reviews the state of the art in trabecular bone biomechanics, focusing on the mechanical aspects, and attempts to identify important areas of current and future research.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.307
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    HERMAN P. SCHWAN: A Scientist and Pioneer in Biomedical Engineering (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 1-27 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092001.093625
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    ROLES FOR LEARNING SCIENCES AND LEARNING TECHNOLOGIES IN BIOMEDICAL ENGINEERING EDUCATION: A Review of Recent Advances (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 29-48 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Education in biomedical engineering offers a number of challenges to all constituents of the educational process-faculty, students, and employers of graduates. Although biomedical engineering educational systems have been under development for 40 years, interest in and the pace of development of these programs has accelerated in recent years. New advances in the learning sciences have provided a framework for the reexamination of instructional paradigms in biomedical engineering. This work shows that learning environments should be learner centered, knowledge centered, assessment centered, and community centered. In addition, learning technologies offer the potential to achieve this environment with efficiency. Biomedical engineering educators are in a position to design and implement new learning systems that can take advantage of advances in learning science, learning technology, and reform in engineering education.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.091701.125502
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    BIOENGINEERING OF THERAPEUTIC AEROSOLS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 93-107 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The new field of therapeutic aerosol bioengineering (TAB), driven primarily by the medical need for inhaled insulin, is now expanding to address medical needs ranging from respiratory to systemic diseases, including asthma, growth deficiency, and pain. Bioengineering of therapeutic aerosols involves a level of aerosol particle design absent in traditional therapeutic aerosols, which are created by conventionally spraying a liquid solution or suspension of drug or milling and mixing a dry drug form into respirable particles. Bioengineered particles may be created in liquid form from devices specially designed to create an unusually fine size distribution, possibly with special purity properties, or solid particles that possess a mixture of drug and excipient, with designed shape, size, porosity, and drug release characteristics. Such aerosols have enabled several high-visibility clinical programs of inhaled insulin, as well as earlier-stage programs involving inhaled morphine, growth hormone, beta-interferon, alpha-1-antitrypsin, and several asthma drugs. The design of these aerosols, limited by partial knowledge of the lungs' physiological environment, and driven largely at this stage by market forces, relies on a mixture of new and old science, pharmaceutical science intuition, and a degree of biological-impact empiricism that speaks to the importance of an increased level of academic involvement.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.100101.132311
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    MECHANO-ELECTROCHEMICAL PROPERTIES OF ARTICULAR CARTILAGE: Their Inhomogeneities and Anisotropies (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 175-209 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In this chapter, the recent advances in cartilage biomechanics and electromechanics are reviewed and summarized. Our emphasis is on the new experimental techniques in cartilage mechanical testing, new experimental and theoretical findings in cartilage biomechanics and electromechanics, and emerging theories and computational modeling of articular cartilage. The charged nature and depth-dependent inhomogeneity in mechano-electrochemical properties of articular cartilage are examined, and their importance in the normal and/or pathological structure-function relationships with cartilage is discussed, along with their pathophysiological implications. Developments in theoretical and computational models of articular cartilage are summarized, and their application in cartilage biomechanics and biology is reviewed. Future directions in cartilage biomechanics and mechano-biology research are proposed.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.110701.120309
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    ADVANCES IN IN VIVO BIOLUMINESCENCE IMAGING OF GENE EXPRESSION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 235-260 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract To advance our understanding of biological processes as they occur in living animals, imaging strategies have been developed and refined that reveal cellular and molecular features of biology and disease in real time. One rapid and accessible technology for in vivo analysis employs internal biological sources of light emitted from luminescent enzymes, luciferases, to label genes and cells. Combining this reporter system with the new generation of charge coupled device (CCD) cameras that detect the light transmitted through the animal's tissues has opened the door to sensitive in vivo measurements of mammalian gene expression in living animals. Here, we review the development and application of this imaging strategy, in vivo bioluminescence imaging (BLI), together with in vivo fluorescence imaging methods, which has enabled the real-time study of immune cell trafficking, of various genetic regulatory elements in transgenic mice, and of in vivo gene transfer. BLI has been combined with fluorescence methods that together offer access to in vivo measurements that were not previously available. Such studies will greatly facilitate the functional analysis of a wide range of genes for their roles in health and disease.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.111901.093336
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    PHYSICS AND APPLICATIONS OF MICROFLUIDICS IN BIOLOGY (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 261-286 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.112601.125916
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    ADVANCES IN PROTEOMIC TECHNOLOGIES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 349-373 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Proteomics is a rapidly emerging set of key technologies that are being used to identify proteins and map their interactions in a cellular context. With the sequencing of the human genome, the scope of proteomics has shifted from protein identification and characterization to include protein structure, function and protein-protein interactions. Technologies used in proteomic research include two-dimensional gel electrophoresis, mass spectrometry, yeast two-hybrids screens, and computational prediction programs. While some of these technologies have been in use for a long time, they are currently being applied to study physiology and cellular processes in high-throughput formats. It is the high-throughput approach that defines and characterizes modern proteomics. In this review, we discuss the current status of these experimental and computational technologies relevant to the three major aspects of proteomics-characterization of proteomes, identification of proteins, and determination of protein function. We also briefly discuss the development of new proteomic technologies that are based on recent advances in analytical and biochemical techniques, engineering, microfabrication, and computational prowess. The integration of these advances with established technologies is invaluable for the drive toward a comprehensive understanding of protein structure and function in the cellular milieu.
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    MASS TRANSPORT IN ARTERIES AND THE LOCALIZATION OF ATHEROSCLEROSIS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 79-118 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Atherosclerosis is a disease of the large arteries that involves a characteristic accumulation of high-molecular-weight lipoprotein in the arterial wall. This review focuses on the mass transport processes that mediate the focal accumulation of lipid in arteries and places particular emphasis on the role of fluid mechanical forces in modulating mass transport phenomena. In the final analysis, four mass transport mechanisms emerge that may be important in the localization of atherosclerosis: blood phase controlled hypoxia, leaky endothelial junctions, transient intercellular junction remodeling, and convective clearance of the subendothelial intima and media. Further study of these mechanisms may contribute to the development of therapeutic strategies for atherosclerotic diseases.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121529
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    SELECTED METHODS FOR IMAGING ELASTIC PROPERTIES OF BIOLOGICAL TISSUES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 57-78 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract For millennia, physicians have used palpation as a part of the physical examination to detect pathology. The ubiquitous presence of "stiffer" tissue associated with pathology often represents an early warning sign for disease, as in the cases of breast or prostate cancer. Very often tumors are found at surgery that were occult even with modern imaging instruments. This implies that methods for estimating "hardness" of tissues would add a weapon to the medical armamentarium. To this end, this review discusses several methods of estimating tissue hardness using internal or external means of applying stress (force per unit area) and several associated methods of detecting the resulting strain (fractional length change) in an effort to image a tissue mechanical property, such as Young's modulus (ratio of stress to strain). Some investigators have developed methods of estimating stiffness or modulus, but most methods result in qualitative images of stiffness. Nevertheless, such estimates may add a great deal of information not currently available to the current field of medical imaging.
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    THE ENGINEERING OF GENE REGULATORY NETWORKS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 179-206 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121553
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    ENGINEERED NANOMATERIALS FOR BIOPHOTONICS APPLICATIONS: Improving Sensing, Imaging, and Therapeutics (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 285-292 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120723
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    BIOMONITORING WITH WIRELESS COMMUNICATIONS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 383-412 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Wireless biomonitoring, first used in human beings for fetal heart-rate monitoring more than 30 years ago, has now become a technology for remote sensing of patients' activity, blood pulse pressure, oxygen saturation, internal pressures, orthopedic device loading, and gastrointestinal endoscopy. Technical advances in miniaturization and wireless communications have enabled development of monitoring devices that can be made available for general use by individuals/patients and caregivers. New methods for short-range wireless communications not encumbered by radio spectrum restrictions (e.g., ultra-wideband) will enable applications of wireless monitoring without interference in ambulatory subjects, in home care, and in hospitals.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121653
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    STRUCTURAL, FUNCTIONAL, AND MOLECULAR MR IMAGING OF THE MICROVASCULATURE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 29-56 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121606
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    MODELING TOTAL HEART FUNCTION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 147-177 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.
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    MULTIAXIAL MECHANICAL BEHAVIOR OF BIOLOGICAL MATERIALS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 251-284 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: For native and engineered biological tissues, there exist many physiological, surgical, and medical device applications where multiaxial material characterization and modeling is required. Because biological tissues and many biocompatible elastomers are incompressible, planar biaxial testing allows for a two-dimensional (2-D) stress-state that can be used to fully characterize their three-dimensional (3-D) mechanical properties. Biological tissues exhibit complex mechanical behaviors not easily accounted for in classic elastomeric constitutive models. Accounting for these behaviors by careful experimental evaluation and formulation of constitutive models continues to be a challenging area in biomechanical modeling and simulation. The focus of this review is to describe the application of multiaxial testing techniques to soft tissues and their relation to modern biomechanical constitutive theories.
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    NEURAL TISSUE ENGINEERING: Strategies for Repair and Regeneration (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 293-347 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120731
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    BLOOD VESSEL CONSTITUTIVE MODELS-1995-2002 (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 413-439 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Knowledge of blood vessel mechanical properties is fundamental to the understanding of vascular function in health and disease. Analytic results can help physicians in the clinic, both in designing and in choosing appropriate therapies. Understanding the mechanical response of blood vessels to physiologic loads is necessary before ideal therapeutic solutions can be realized. For this reason, blood vessel constitutive models are needed. This article provides a critical review of recent blood vessel constitutive models, starting with a brief overview of the structure and function of arteries and veins, followed by a discussion of experimental techniques used in the characterization of material properties. Current models are classified by type, including pseudoelastic, randomly elastic, poroelastic, and viscoelastic. Comparisons are presented between the various models and existing experimental data. Applications of blood vessel constitutive models are also briefly presented, followed by the identification of future directions in research.
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    THE NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 1-26 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.062403.131947
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    FRACTAL ANALYSIS OF THE VASCULAR TREE IN THE HUMAN RETINA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 427-452 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    TISSUE GROWTH AND REMODELING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 77-107 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.
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    OPTICAL PROJECTION TOMOGRAPHY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 209-228 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.
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    QUANTUM DOTS AS CELLULAR PROBES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 55-76 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Robust and bright light emitters, semiconductor nanocrystals [quantum dots (QDs)] have been adopted as a new class of fluorescent labels. Six years after the first experiments of their uses in biological applications, there have been dramatic improvements in understanding surface chemistry, biocompatibility, and targeting specificity. Many studies have shown the great potential of using quantum dots as new probes in vitro and in vivo. This review summarizes the recent advances of quantum dot usage at the cellular level, including immunolabeling, cell tracking, in situ hybridization, FRET, in vivo imaging, and other related technologies. Limitations and potential future uses of quantum dot probes are also discussed.
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    INSTRUMENTATION ASPECTS OF ANIMAL PET (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 255-285 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Biological research has been accelerated by the development of noninvasive imaging techniques and by use of genetically engineered mice to model human diseases and normal development. Because these mice can be expensive, noninvasive imaging techniques, such as high-resolution positron emission tomography (PET), that permit longitudinal studies of the same animals are very attractive. Such studies reduce the number of animals used, reduce intersubject variability, and improve the accuracy of biological models. PET provides quantitative measurements of the spatiotemporal distribution of radiotracers and is an extremely powerful tool in using molecular imaging to study biology, to monitor disease intervention, and to establish pharmacokinetics for new drugs. The design of animal PET scanners has improved significantly in the past decade and can provide adequate image resolution and sensitivity to study transgenic mice. This article reviews the fundamental and technical challenges of small-animal PET imaging, with a particular focus on the latest developments and future directions of detector technologies and system design.
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    DETERMINISTIC AND STOCHASTIC ELEMENTS OF AXONAL GUIDANCE (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 187-221 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: An enormous literature has been developed on investigations of the growth and guidance of axons during development and after injury. In this review, we provide a guide to this literature as a resource for biomedical investigators. We first review briefly the molecular biology that is known to regulate migration of the growth cone and branching of axonal arbors. We then outline some important fundamental considerations that are important to the modeling of the phenomenology of these guidance effects and of what is known of their underlying internal mechanisms. We conclude by providing some thoughts on the outlook for future biomedical modeling in the field.
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    BIOCHEMISTRY AND BIOMECHANICS OF CELL MOTILITY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 105-150 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Cell motility is an essential cellular process for a variety of biological events. The process of cell migration requires the integration and coordination of complex biochemical and biomechanical signals. The protrusion force at the leading edge of a cell is generated by the cytoskeleton, and this force generation is controlled by multiple signaling cascades. The formation of new adhesions at the front and the release of adhesions at the rear involve the outside-in and inside-out signaling mediated by integrins and other adhesion receptors. The traction force generated by the cell on the extracellular matrix (ECM) regulates cell-ECM adhesions, and the counter force exerted by ECM on the cell drives the migration. The polarity of cell migration can be amplified and maintained by the feedback loop between the cytoskeleton and cell-ECM adhesions. Cell migration in three-dimensional ECM has characteristics distinct from that on two-dimensional ECM. The migration of cells is initiated and modulated by external chemical and mechanical factors, such as chemoattractants and the mechanical forces acting on the cells and ECM, as well as the surface density, distribution, topography, and rigidity of the ECM.
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    FUNCTIONAL ELECTRICAL STIMULATION FOR NEUROMUSCULAR APPLICATIONS * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 327-360 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Paralyzed or paretic muscles can be made to contract by applying electrical currents to the intact peripheral motor nerves innervating them. When electrically elicited muscle contractions are coordinated in a manner that provides function, the technique is termed functional electrical stimulation (FES). In more than 40 years of FES research, principles for safe stimulation of neuromuscular tissue have been established, and methods for modulating the strength of electrically induced muscle contractions have been discovered. FES systems have been developed for restoring function in the upper extremity, lower extremity, bladder and bowel, and respiratory system. Some of these neuroprostheses have become commercialized products, and others are available in clinical research settings. Technological developments are expected to produce new systems that have no external components, are expandable to multiple applications, are upgradable to new advances, and are controlled by a combination of signals, including biopotential signals from nerve, muscle, and the brain.
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    PIERRE M. GALLETTI: A Personal Reflection (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 1-7 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Pierre Galletti, my friend and colleague, passed away on March 8, 1997, having left his mark on the emerging field of biomedical engineering. He was a pioneering researcher, making his impact in such fields as heart-lung bypass, artificial organs, and tissue engineering. He was a dedicated teacher and a mentor to many. He not only provided leadership in the establishment of the medical school at Brown University, but also helped start Morehouse School of Medicine in Atlanta. He was an entrepreneur and an individual who realized that ultimately basic science only impacts patient care when new technology is made available to the public. He served the bioengineering community in many ways, later in life becoming active in public policy, and as the second president of the American Institute for Medical and Biological Engineering, more than anyone focused this organization on its public policy role. He was the consummate biomedical engineer, a person of great vision, a man for all seasons.
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    PHYSICOCHEMICAL FOUNDATIONS AND STRUCTURAL DESIGN OF HYDROGELS IN MEDICINE AND BIOLOGY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 9-29 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.
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    INJURY AND REPAIR OF LIGAMENTS AND TENDONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 83-118 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In this chapter, biomechanical methods used to analyze healing and repair of ligaments and tendons are initially described such that the tensile properties of these soft tissues as well as their contribution to joint motion can be determined. The focus then turns to the important mechanical and biological factors that improve the healing process of ligaments. The biomechanics of surgical reconstruction of the anterior cruciate ligament and the key surgical parameters that affect the performance of the replacement grafts are subsequently reviewed. Finally, injury mechanisms and the biomechanical analysis of various treatment techniques for various types of tendon injuries are described.
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    CELL MECHANICS: Mechanical Response, Cell Adhesion, and Molecular Deformation (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 189-226 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract As the basic unit of life, the cell is a biologically complex system, the understanding of which requires a combination of various approaches including biomechanics. With recent progress in cell and molecular biology, the field of cell mechanics has grown rapidly over the last few years. This review synthesizes some of these recent developments to foster new concepts and approaches, and it emphasizes molecular-level understanding. The focuses are on the common themes and interconnections in three related areas: (a) the responses of cells to mechanical forces, (b) the mechanics and kinetics of cell adhesion, and (c) the deformation of biomolecules. Specific examples are also given to illustrate the quantitative modeling used in analyzing biological processes and physiological functions.
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    CONTROL MOTIFS FOR INTRACELLULAR REGULATORY NETWORKS1 (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 391-419 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract A number of technological innovations are yielding unprecedented data on the networks of biochemical, genetic, and biophysical reactions that underlie cellular behavior and failure. These networks are composed of hundreds to thousands of chemical species and structures, interacting via nonlinear and possibly stochastic physical processes. A central goal of modern biology is to optimally use the data on these networks to understand how their design leads to the observed cellular behaviors and failures. Ultimately, this knowledge should enable cellular engineers to redesign cellular processes to meet industrial needs (such as optimal natural product synthesis), aid in choosing the most effective targets for pharmaceuticals, and tailor treatment for individual genotypes. The size and complexity of these networks and the inevitable lack of complete data, however, makes reaching these goals extremely difficult. If it proves possible to modularize these networks into functional subnetworks, then these smaller networks may be amenable to direct analysis and might serve as regulatory motifs. These motifs, recurring elements of control, may help to deduce the structure and function of partially known networks and form the basis for fulfilling the goals described above. A number of approaches to identifying and analyzing control motifs in intracellular networks are reviewed.
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    THREE-DIMENSIONAL CONFOCAL MICROSCOPY OF THE LIVING HUMAN EYE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 69-91 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Three-dimensional confocal microscopy of the living eye is a major development in instrumentation for biomicroscopy of the eye. This noninvasive optical technology has its roots in the application of optics to reflected light imaging of the eye. These instrument developments began with Leeuwenhoek's use of his single lens microscope to investigate the structure of the eye. There followed a series of connected instruments: the ophthalmoscope, the slit lamp, the specular microscope, and the clinical confocal microscope. In vivo confocal microscopy produces high contrast, reflected light images or optical sections through the depth of living ocular tissue. Stacks of registered optical sections can be transformed by computer visualization techniques into three-dimensional volume images of ocular tissues: cornea, ocular lens, retina, and optic nerve. The clinical confocal microscope has resulted in new diagnostic techniques and new cellular descriptions of ocular disorders and pathology.
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    DENATURATION OF COLLAGEN VIA HEATING: An Irreversible Rate Process (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 109-128 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Heating therapies are increasingly used in cardiology, dermatology, gynecology, neurosurgery, oncology, ophthalmology, orthopedics, and urology, among other medical specialties. This widespread use of heating is driven primarily by the availability of new technology, not by a detailed understanding of the biothermomechanics. Without basic quantification of the underlying physical and chemical processes in terms of parameters that can be controlled clinically, identification of preferred interventions will continue to be based primarily on trial and error, thus necessitating large clinical studies and years of accumulative experience. Perusal of the literature reveals that much has been learned over the past century about the response of cells, proteins, and tissues to supra-physiologic temperatures; yet, the associated findings are reported in diverse journals and the underlying basic processes remain unidentified. In this review, we seek to contrast various findings on the kinetics of the thermal denaturation of collagen and to encourage investigators to consider the many open problems in part via a synthesis of results from the diverse literatures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.101001.131546
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    FUNDAMENTALS OF IMPACT BIOMECHANICS: Part I - Biomechanics of the Head, Neck, and Thorax (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 55-81 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract This is the first of two chapters dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in this first chapter are the head, neck, and thorax. The next chapter will discuss the abdomen, pelvis, and the lower extremities. Although the principal thrust of the research has been toward the mitigation of injuries sustained by automotive crash victims, the results of this research have applications in aircraft safety, contact sports, and protection of military personnel and civilians from intentional injury, such as in the use of nonlethal weapons. The reader should be keenly aware of the wide variation in human response and tolerance data in the cited results. This is due primarily to the large biological variation among humans and to the effects of aging. Average values are useful in design but cannot be applied to individuals.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.55
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    CRYOSURGERY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 157-187 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Cryosurgery is a surgical technique that employs freezing to destroy undesirable tissue. Developed first in the middle of the nineteenth century it has recently incorporated new imaging technologies and is a fast growing minimally invasive surgical technique. A historical review of the field of cryosurgery is presented, showing how technological advances have affected the development of the field. This is followed by a more in-depth survey of two important topics in cryosurgery: (a) the biochemical and biophysical mechanisms of tissue destruction during cryosurgery and (b) monitoring and imaging techniques for cryosurgery.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.157
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    QUANTITATIVE MEASUREMENT AND PREDICTION OF BIOPHYSICAL RESPONSE DURING FREEZING IN TISSUES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 257-288 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Cryopreservation and cryosurgery are important biomedical applications used to selectively preserve or destroy cellular systems through freezing. Studies using cryomicroscopy techniques, which allow the visualization of the freezing process in single cells, have shown that a drop in viability correlates with the extent of two biophysical events during the freezing process: (a) intracellular ice formation and (b) cellular dehydration. These same biophysical events operate in tissue systems; however, the inability to visualize and quantify the dynamics of the freezing process in tissues has hampered direct correlation of these events with freezing-induced changes in viability. This review highlights two new techniques that use freeze substitution and differential scanning calorimetry to provide dynamic freezing data in tissue. Characteristic dimensions and parameters extracted from these new data are then used in a predictive model of biophysical freezing response in several tissues, including liver and tumor. This approach promises to help guide improved design of both cryopreservation and cryosurgical applications of tissue freezing.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.257
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    ANTIBODY ENGINEERING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 339-376 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Antibodies are unique in their high affinity and specificity for a binding partner, a quality that has made them one of the most useful molecules for biotechnology and biomedical applications. The field of antibody engineering has changed rapidly in the past 10 years, fueled by novel technologies for the in vitro isolation of antibodies from combinatorial libraries and their functional expression in bacteria. This review presents an overview of the methods available for the de novo generation of human antibodies, for engineering antibodies with increased antigen affinity, and for the production of antibody fragments. Select applications of recombinant antibodies are also presented.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.339
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    NEW CURRENTS IN ELECTRICAL STIMULATION OF EXCITABLE TISSUES1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 377-397 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Electric fields can stimulate excitable tissue by a number of mechanisms. A uniform long, straight peripheral axon is activated by the gradient of the electric field that is oriented parallel to the fiber axis. Cortical neurons in the brain are excited when the electric field, which is applied along the axon-dendrite axis, reaches a particular threshold value. Cardiac tissue is thought to be depolarized in a uniform electric field by the curved trajectories of its fiber tracts. The bidomain model provides a coherent conceptual framework for analyzing and understanding these apparently disparate phenomena. Concepts such as the activating function and virtual anode and cathode, as well as anode and cathode break and make stimulation, are presented to help explain these excitation events in a unified manner. This modeling approach can also be used to describe the response of excitable tissues to electric fields that arise from charge redistribution (electrical stimulation) and from time-varying magnetic fields (magnetic stimulation) in a self-consistent manner. It has also proved useful to predict the behavior of excitable tissues, to test hypotheses about possible excitation mechanisms, to design novel electrophysiological experiments, and to interpret their findings.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.377
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    CURRENT METHODS IN MEDICAL IMAGE SEGMENTATION1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 315-337 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Image segmentation plays a crucial role in many medical-imaging applications, by automating or facilitating the delineation of anatomical structures and other regions of interest. We present a critical appraisal of the current status of semiautomated and automated methods for the segmentation of anatomical medical images. Terminology and important issues in image segmentation are first presented. Current segmentation approaches are then reviewed with an emphasis on the advantages and disadvantages of these methods for medical imaging applications. We conclude with a discussion on the future of image segmentation methods in biomedical research.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.315
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    BLOOD VESSEL CONSTITUTIVE MODELS-1995-2002 (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 413-439 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Knowledge of blood vessel mechanical properties is fundamental to the understanding of vascular function in health and disease. Analytic results can help physicians in the clinic, both in designing and in choosing appropriate therapies. Understanding the mechanical response of blood vessels to physiologic loads is necessary before ideal therapeutic solutions can be realized. For this reason, blood vessel constitutive models are needed. This article provides a critical review of recent blood vessel constitutive models, starting with a brief overview of the structure and function of arteries and veins, followed by a discussion of experimental techniques used in the characterization of material properties. Current models are classified by type, including pseudoelastic, randomly elastic, poroelastic, and viscoelastic. Comparisons are presented between the various models and existing experimental data. Applications of blood vessel constitutive models are also briefly presented, followed by the identification of future directions in research.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120719
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    THE NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 1-26 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.062403.131947
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    THE TISSUE ENGINEERING PUZZLE: A Molecular Perspective (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 441-463 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The inability of biomaterial scaffolds to functionally integrate into surrounding tissue is one of the major roadblocks to developing new biomaterials and tissue-engineering scaffolds. Despite considerable advances, current approaches to engineering cell-surface interactions fall short in mimicking the complexity of signals through which surrounding tissue regulates cell behavior. Cells adhere and interact with their extracellular environment via integrins, and their ability to activate associated downstream signaling pathways depends on the character of adhesion complexes formed between cells and their extracellular matrix. In particular, alpha5beta1 and alphavbeta3 integrins are central to regulating downstream events, including cell survival and cell-cycle progression. In contrast to previous findings that alphavbeta3 integrins promote angiogenesis, recent evidence argues that alphavbeta3 integrins may act as negative regulators of proangiogenic integrins such as alpha5beta1. This suggests that fibronectin is critical for scaffold vascularization because it is the only mammalian adhesion protein that binds and activates alpha5beta1 integrins. Cells are furthermore capable of stretching fibronectin matrices such that the protein partially unfolds, and recent computational simulations provide structural models of how mechanical stretching affects fibronectin function. We propose a model whereby excessive tension generated by cells in contact to biomaterials may in fact render fibronectin fibrils nonangiogenic and potentially inhibit vascularization. The model could explain why current biomaterials independent of their surface chemistries and textures fail to vascularize.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121615
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    ENGINEERING SYNTHETIC VECTORS FOR IMPROVED DNA DELIVERY: Insights from Intracellular Pathways (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 397-426 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Significant progress has been made in the area of nonviral gene delivery to date. Yet, synthetic vectors remain less efficient by orders of magnitude than their viral counterparts. Research continues toward unraveling and overcoming various barriers to the efficient delivery of DNA, whether in plasmid form encoding a gene or as an oligonucleotide for the selective inhibition of target gene expression. Novel components for overcoming these hurdles are continually being incorporated into the design of synthetic vectors, leading to increasingly more virus-like particles. Despite these advances, general principles defining the design of synthetic vectors are yet to be developed fully. A more quantitative analysis of the cellular uptake and intracellular processing of these vectors is required for the rational manipulation of vector design. Mathematical frameworks with a more conceptual basis will help obtain an integrated perspective on these complex systems. In this review, we critically examine the progress made toward the improved design of synthetic vectors by the strategic exploitation of intracellular mechanisms and explore newer possibilities to overcome obstacles in the practical realization of this field.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140203
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    TISSUE ENGINEERING APPLICATIONS OF THERAPEUTIC CLONING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 27-40 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.012204.115707
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    BREAST TISSUE ENGINEERING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 109-130 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Tissue engineering has the potential to redefine rehabilitation for the breast cancer patient by providing a translatable strategy that restores the postmastectomy breast mound while concomitantly obviating limitations realized with contemporary reconstructive surgery procedures. The engineering design goal is to provide a sufficient volume of viable fat tissue based on a patient's own cells such that deficits in breast volume can be abrogated. To be sure, adipose tissue engineering is in its infancy, but tremendous strides have been made. Numerous studies attest to the feasibility of adipose tissue engineering. The field is now poised to challenge barriers to clinical translation that are germane to most tissue engineering applications, namely scale-up, large animal model development, and vascularization. The innovative and rapid progress of adipose engineering to date, as well as opportunities for its future growth, is presented.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140032
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    FUNCTIONAL EFFICACY OF TENDON REPAIR PROCESSES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 303-329 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Despite various attempts to repair and replace injured tendon, an understanding of the repair processes and a systematic approach to achieving functional efficacy remain elusive. In this review the epidemiology of tendon injury and repair is first examined. Using a traditional paradigm for repair assessment, the biology and biomechanics of normal tendon, natural healing, and repair are then explored. New treatment strategies such as functional tissue engineering are discussed, including a functional approach to treatment that involves the development of in vivo functional design parameters to judge the acceptability of a repair outcome. The paper concludes with future directions.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140240
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    TISSUE ENGINEERING OF LIGAMENTS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 131-156 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Tissue engineering is emerging as a significant clinical option to address tissue and organ failure by implanting biological substitutes for the compromised tissues. As compared to the transplantation of cells alone, engineered tissues offer the potential advantage of immediate functionality. Engineered tissues can also serve as physiologically relevant models for controlled studies of cells and tissues designed to distinguish the effects of specific signals from the complex milieu of factors present in vivo. A high number of ligament failures and the lack of adequate options to fully restore joint functions have prompted the need to develop new tissue engineering strategies. We discuss the requirements for ligament reconstruction, the available treatment options and their limitations, and then focus on the tissue engineering of ligaments. One representative tissue engineering system involving the integrated use of adult human stem cells, custom-designed scaffolds, and advanced bioreactors with dynamic loading is described.
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    RETINAL PROSTHESIS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 361-401 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Retinal prostheses represent the best near-term hope for individuals with incurable, blinding diseases of the outer retina. On the basis of the electrical activation of nerves, prototype retinal prostheses have been tested in blind humans and have demonstrated the capability to elicit the sensation of light and to give test subjects the ability to detect motion. To improve the visual function in implant recipients, a more sophisticated device is required. Simulations suggest that 600Đ??1000 pixels will be required to provide visual function such as face recognition and reading. State-of-the-art implantable stimulator technology cannot produce such a device, which mandates the advancement of the state of the art in areas such as analog microelectronics, wireless power and data transfer, packaging, and stimulating electrodes.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100435
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    BLOOD-ON-A-CHIP (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 77-103 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.011205.135108
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    MICRO-COMPUTED TOMOGRAPHY-CURRENT STATUS AND DEVELOPMENTS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 185-208 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The recent rapid increase in interest in tomographic imaging of small animals and of human (and large animal) organ biopsies is driven largely by drug discovery, cancer detection/monitoring, phenotype identification and/or characterization, and development of disease detection methods and monitoring efficacies of drugs in disease treatment. In biomedical applications, micro-computed tomography (CT) scanners can function as scaled-down (i.e., mini) clinical CT scanners that provide a three-dimensional (3-D) image of most, if not the entire, torso of a mouse at image resolution (50-100 mum) scaled proportional to that of a human CT image. Micro-CT scanners, on the other hand, image specimens the size of intact rodent organs at spatial resolutions from cellular (20 mum) down to subcellular dimensions (e.g., 1 mum) and fill the resolution-hiatus between microscope imaging, which resolves individual cells in thin sections of tissue, and mini-CT imaging of intact volumes.
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    MOLECULAR MACHINES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 363-395 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Molecular machines are tiny energy conversion devices on the molecular-size scale. Whether naturally occurring or synthetic, these machines are generally more efficient than their macroscale counterparts. They have their own mechanochemistry, dynamics, workspace, and usability and are composed of nature's building blocks: namely proteins, DNA, and other compounds, built atom by atom. With modern scientific capabilities it has become possible to create synthetic molecular devices and interface them with each other. Countless such machines exist in nature, and it is possible to build artificial ones by mimicking nature. Here we review some of the known molecular machines, their structures, features, and characteristics. We also look at certain devices in their early development stages, as well as their future applications and challenges.
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    ROBOTICS, MOTOR LEARNING, AND NEUROLOGIC RECOVERY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 497-525 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140223
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    ADVANCES IN HIGH-FIELD MAGNETIC RESONANCE IMAGING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 157-184 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Among advances in magnetic resonance imaging (MRI), the increase of the magnetic field strength is perhaps one of the most significant. The use of high magnetic fields for in vivo magnetic resonance is motivated by a number of considerations. Advantages are increases in signal-to-noise ratio, blood-oxygenation level-dependent contrast, and spectral resolution, while disadvantages include potential reduction of contrast in anatomic imaging owing to lengthening of T1 and effects of susceptibility of high fields. To address these challenges, technical advances have been made in various aspects of MRI, allowing high-field MRI to provide exquisite morphological and functional details in clinical and research settings. This review provides an overview of technical issues and applications of high-field MRI.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140017
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    MECHANICAL BIOEFFECTS OF ULTRASOUND (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 229-248 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool. Through both thermal and nonthermal mechanisms, ultrasound can produce a variety of biological effects in tissues in vitro and in vivo. This chapter provides an overview of the fundamentals of key nonthermal mechanisms for the interaction of ultrasound with biological tissues. Several categories of mechanical bioeffects of ultrasound are then reviewed to provide insight on the range of ultrasound bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the potential application of mechanical bioeffects to the design of new therapeutic applications of ultrasound in medicine.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140126
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    OCULAR BIOMECHANICS AND BIOTRANSPORT (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 249-273 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The eye transduces light, and we usually do not think of it as a biomechanical structure. Yet it is actually a pressurized, thick-walled shell that has an internal and external musculature, a remarkably complex internal vascular system, dedicated fluid production and drainage tissues, and a variety of specialized fluid and solute transport systems. Biomechanics is particularly involved in accommodation (focusing near and far), as well as in common disorders such as glaucoma, macular degeneration, myopia, and presbyopia. In this review, we give a (necessarily brief) overview of many of the interesting biomechanical aspects of the eye, concluding with a list of open problems.
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    DNA MECHANICS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 21-53 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: We review the history of DNA mechanics and its analysis. We evaluate several methods to analyze the structures of superhelical DNA molecules, each predicated on the assumption that DNA can be modeled with reasonable accuracy as an extended, linearly elastic polymer. Three main approaches are considered: mechanical equilibrium methods, which seek to compute minimum energy conformations of topologically constrained molecules; statistical mechanical methods, which seek to compute the Boltzmann distribution of equilibrium conformations that arise in a finite temperature environment; and dynamic methods, which seek to compute deterministic trajectories of the helix axis by solving equations of motion. When these methods include forces of self-contact, which prevent strand passage and preserve the topological constraint, each predicts plectonemically interwound structures. On the other hand, the extent to which these mechanical methods reliably predict energetic and thermodynamic properties of superhelical molecules is limited, in part because of their inability to account explicitly for interactions involving solvent. Monte Carlo methods predict the entropy associated with supercoiling to be negative, in conflict with a body of experimental evidence that finds it is large and positive, as would be the case if superhelical deformations significantly disrupt the ordering of ambient solvent molecules. This suggests that the large-scale conformational properties predicted by elastomechanical models are not the only ones determining the energetics and thermodynamics of supercoiling. Moreover, because all such models that preserve the topological constraint correctly predict plectonemic interwinding, despite these and other limitations, this constraint evidently dominates energetic and thermodynamic factors in determining supercoil geometry. Therefore, agreement between predicted structures and structures obtained experimentally, for example, by electron microscopy, does not in itself provide evidence for the correctness or completeness of any given model of DNA mechanics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.062403.132016
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    MOLECULAR MECHANICS AND DYNAMICS OF LEUKOCYTE RECRUITMENT DURING INFLAMMATION (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 151-185 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Discovery of new genes and proteins directly supporting leukocyte adhesion is waning, whereas there is heightened interest in the cell mechanics and receptor dynamics that lead from transient tethering via selectins to affinity shifts and adhesion strengthening through integrins. New optical tools enable real-time imaging of leukocyte rolling and arrest in parallel plate flow channels (PPFCs), and detection of single-molecule force spectroscopy provides an inner view of the intercellular adhesive contact region. Leukocyte recruitment during acute inflammation is triggered by ligation of G proteinĐ??coupled chemotactic receptors (GPCRs) and clustering of selectins. This, in turn, activates ?‚2-integrin (CD18), which facilitates cell capture and arrest in shear flow. This review provides a conceptual model for the molecular events supporting leukocyte recruitment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100423
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    IN VIVO MAGNETIC RESONANCE SPECTROSCOPY IN CANCER (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 287-326 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Magnetic resonance spectroscopy (MRS) has been used for more than two decades to interrogate metabolite distributions in living cells and tissues. Techniques have been developed that allow multiple spectra to be obtained simultaneously with individual volume elements as small as 1 uL of tissue (i.e., 1 ?? 1 ?? 1 mm3). The most common modern applications of in vivo MRS use endogenous signals from 1H, 31P, or 23Na. Important contributions have also been made using exogenous compounds containing 19F, 13C, or 17O. MRS has been used to investigate cardiac and skeletal muscle energetics, neurobiology, and cancer. This review focuses on the latter applications, with specific reference to the measurement of tissue choline, which has proven to be a tumor biomarker that is significantly affected by anticancer therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100411
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    WERNER GOLDSMITH: Life and Work (1924Đ??2003) (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 1-20 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Werner Goldsmith, one of the foremost authorities on the mechanics of impact and the biomechanics of head and neck injuries, died peacefully at home in Oakland, California, on August 23, 2003, at age 79 after a short, courageous battle with leukemia, ending a long and very distinguished career in mechanics, dynamics, and biomechanics, and an almost six-decades-long association with the University of California, Berkeley. He was one of the pioneering, eminent solid and fluid mechanicians who made an early transition to biomechanics, and in rising to equal distinction in their new fields, added great credibility to biomechanics as a discipline in its own right. He was also a distinguished and influential figure in bioengineering education at his own institution, and, more broadly, in the United States and abroad. An emeritus professor for over a decade, he continued to be active in research and teaching until the very last days of his life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100348
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    FUNDAMENTALS OF IMPACT BIOMECHANICS: Part 2-Biomechanics of the Abdomen, Pelvis, and Lower Extremities (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 27-55 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract This is the second of two chapters (the first chapter appeared in the Annual Review of Biomedical Engineering, 2000, 2:55-81) dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in the first chapter were the head, neck, and thorax. In this chapter, the abdomen, pelvis, and lower extremities are discussed. The thoracolumbar spine is not covered because of length limitations and the low frequency of injury to this area from automotive accidents. Again, in the cited results, the reader needs to be keenly aware of the wide variation in human response and tolerance. This is due primarily to the large biological variations among humans and to the effects of aging. Average values that are useful in design cannot be applied to individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.27
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    VISUAL PROSTHESES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 145-168 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The development of man-made systems to restore functional vision in the profoundly blind has recently undergone a renaissance that has been fueled by a combination of celebrity and government interest, advances in the field of bioengineering, and successes with existing neuroprosthetic systems. This chapter presents the underlying physiologic principles of artificial vision, discusses three contemporary approaches to restoring functional vision in the blind, and concludes by presenting several relevant questions to vision prostheses. While there has been significant progress in the individual components constituting an artificial vision system, the remaining challenge of integrating these components with each other and the nervous system does not lie strictly in the realm of neuroscience, medicine, or engineering but at the interface of all three. In spite of the apparent complexity of an artificial vision system, it is not unreasonable to be optimistic about its eventual success.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.145
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    MICRO- AND NANOMECHANICS OF THE COCHLEAR OUTER HAIR CELL (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 169-194 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Outer hair cell electromotility is crucial for the amplification, sharp frequency selectivity, and nonlinearities of the mammalian cochlea. Current modeling efforts based on morphological, physiological, and biophysical observations reveal transmembrane potential gradients and membrane tension as key independent variables controlling the passive and active mechanics of the cell. The cell's mechanics has been modeled on the microscale using a continuum approach formulated in terms of effective (cellular level) mechanical and electric properties. Another modeling approach is nanostructural and is based on the molecular organization of the cell's membranes and cytoskeleton. It considers interactions between the components of the composite cell wall and the molecular elements within each of its components. The methods and techniques utilized to increase our understanding of the central role outer hair cell mechanics plays in hearing are also relevant to broader research questions in cell mechanics, cell motility, and cell transduction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.169
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    STEM CELL BIOENGINEERING (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 275-305 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Tissue engineering and cellular therapies, either on their own or in combination with therapeutic gene delivery, have the potential to significantly impact medicine. Implementation of technologies based on these approaches requires a readily available source of cells for the generation of cells and tissues outside a living body. Because of their unique capacity to regenerate functional tissue for the lifetime of an organism, stem cells are an attractive "raw material" for multiple biotechnological applications. By definition they are self-renewing because on cell division they can generate daughter stem cells. They are also multipotent because they can differentiate into numerous specialized, functional cells. Recent findings have shown that stem cells exist in most, if not all, tissues, and that stem cell tissue specificity may be more flexible than originally thought. Although the potential for producing novel cell-based products from stem cells is large, currently there are no effective technologically relevant methodologies for culturing stem cells outside the body, or for reproducibly stimulating them to differentiate into functional cells. A mechanistic understanding of the parameters important in the control of stem cell self-renewal and lineage commitment is thus necessary to guide the development of bioprocesses for the ex vivo culture of stem cells and their derivates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.275
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    IMAGE-GUIDED ACOUSTIC THERAPY (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 375-390 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The potential role of therapeutic ultrasound in medicine is promising. Currently, medical devices are being developed that utilize high-intensity focused ultrasound as a noninvasive method to treat tumors and to stop bleeding (hemostasis). The primary advantage of ultrasound that lends the technique so readily to use in noninvasive therapy is its ability to penetrate deep into the body and deliver to a specific site thermal or mechanical energy with submillimeter accuracy. Realizing the full potential of acoustic therapy, however, requires precise targeting and monitoring. Fortunately, several imaging modalities can be utilized for this purpose, thus leading to the concept of image-guided acoustic therapy. This article presents a review of high-intensity focused ultrasound therapy, including its mechanisms of action, the imaging modalities used for guidance and monitoring, some current applications, and the requirements and technology associated with this exciting and promising field.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.375
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