Abstract In this work we present the first comprehensive survey of Brain Interface(BI) technology designs published prior to January 2006. Detailed results from this survey, whichwas based on the Brain Interface Design Framework proposed by Mason and Birch, are presented anddiscussed to address the following research questions: (1) which BI technologies are directlycomparable, (2) what technology designs exist, (3) which application areas (users, activities andenvironments) have been targeted in these designs, (4) which design approaches have received littleor no research and are possible opportunities for new technology, and (5) how well are designsreported. The results of this work demonstrate that meta-analysis of high-level BI design attributesis possible and informative. The survey also produced a valuable, historical cross-reference whereBI technology designers can identify what types of technology have been proposed and by whom.

Keywords Brain; Electroencephalography; Signal Processing, Computer-Assisted;Software

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-169

Abstract The pattern of lung injury induced by the inhalation of ozone (O(3)) dependson the dose delivered to different tissues in the airways. This study examined the distribution ofO(3) uptake in a single, symmetrically branched airway bifurcation. Reaction in the epitheliallining fluid was assumed to be so rapid that O(3) concentration was negligible along the entiresurface of the bifurcation wall. Three-dimensional numerical solutions of the continuity,Navier-Stokes and convection-diffusion equations were obtained for steady inspiratory and expiratoryflows at Reynolds numbers ranging from 100 to 500. The total rate of O(3) uptake was found toincrease with increasing flow rate during both inspiration and expiration. Hot spots of O(3) fluxappeared at the carina of the bifurcation for virtually all inspiratory and expiratory Reynoldsnumbers considered in the simulations. At the lowest expiratory Reynolds number, however, thelocation of the maximum flux was shifted to the outer wall of the daughter branch. For expiratoryflow, additional hot spots of flux were found on the parent branch wall just downstream of thebranching region. In all cases, O(3) uptake in the single bifurcation was larger than that in astraight tube of equal inlet radius and wall surface area. This study provides insight into theeffect of flow conditions on O(3) uptake and dose distribution in individual bifurcations.

Keywords Air Pollutants; Lung; Microfluidics; Models, Biological; Ozone; Pulmonary GasExchange

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-249

Abstract Deep pressure ulcers develop in tissues subjected to sustained mechanicalloading. Though it has been hypothesized that this damage mechanism results from local tissueischemia, it has recently been shown with a cell model that sustained compression can cause celldeformation, leading to tissue breakdown. The present study focuses on the assessment of cellviability during compression and ischemia in an in vitro muscle model to determine their relativecontributions to damage development. A model system was developed consisting of engineered skeletalmuscle produced from the culture of murine muscle cells in a collagen gel. The tissue was subjectedto 0, 20, or 40% compression under hypoxic or normoxic conditions. Experiments were performed on thestage of a microscope and cell viability was monitored using fluorescent markers for apoptotic andnecrotic cell death. Hypoxia did not lead to significant cell death over a 22 h period. By contrast,compression led to immediate cell death that increased withtime. No additional effect of hypoxia oncell death was observed. These data show that contrary to existing theories, compression can causedevelopment of muscle damage and that hypoxia does not contribute to cell death development within22 h in engineered muscle.

Keywords Ischemia; Muscle, Skeletal; Myoblasts; Oxygen; Pressure Ulcer

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-284

Abstract The outcome of both cryopreservation and cryosurgical freezing applicationsis influenced by the concentration and type of the cryoprotective agent (CPA) or the cryodestructiveagent (i.e., the chemical adjuvants referred to here as CDA) added prior to freezing. It alsodepends on the amount and type of crystalline, amorphous and/or eutectic phases formed duringfreezing which can differentially affect viability. This work describes the use of X-ray computertomography (CT) for non-invasive, indirect determination of the phase, solute concentration andtemperature within biomaterials (CPA, CDA loaded solutions and tissues) by X-ray attenuation beforeand after freezing. Specifically, this work focuses on establishing the feasibility of CT (100-420kV acceleration voltage) to accurately measure the concentration of glycerol or salt as model CPAand CDAs in unfrozen solutions and tissues at 20 degrees C, or the phase in frozen solutions andtissue systems at -78.5 and -196 degrees C. The solutions are composed of water with physiologicalconcentrations of NaCl (0.88% wt/wt) and DMEM (Dulbecco’’s Modified Eagle’’s Medium) with addedglycerol (0-8 M). The tissue system is chosen as 3 mm thick porcine liver slices as well as 2 cmdiameter cores which were either imaged fresh (3-4 h cold ischemia) or after loading with DMEM basedglycerol solutions (0-8 M) for times ranging from hours to 7 days at 4 degrees C. The X-rayattenuation is reported in Hounsfield units (HU), a clinical measurement which normalizes X-rayattenuation values by the difference between those of water and air. NaCl solutions from 0 to 23.3%wt/wt (i.e. water to eutectic concentration) were found to linearly correspond to HU in a range from0 to 155. At -196 degrees C the variation was from -80 to 95 HU while at -78.5 degrees C allreadings were roughly 10 HU lower. At 20 degrees C NaCl and DMEM solutions with 0-8 M glycerolloading show a linear variation from 0 to 145 HU. After freezing to -78.5 degrees C the variation ofthe NaCl and DMEMsolutions is more than twice as large between -90 and +190 HU and was distinctlynon-linear above 6 M. After freezing to -196 degrees C the variation of the NaCl and DMEM solutionsincreased even further to -80 to +225 HU and was distinctly non-linear above 4 M, which aftermodeling the phase change and crystallization process is shown to correlate with an amorphous phase.In all tissue systems the HU readings were similar to solutions but higher by roughly 30 HU, aswell as showing some deviations at 0 M after storage, probably due to tissue swelling. The standarddeviations in all measurements were roughly 5 HU or below in all samples. In addition, two practicalexamples for CT use were demonstrated including: (1) glycerol loading and freezing of tissue coresand, (2) a mock cryosurgical procedure. In the loading experiment CT was able to measure thepermeation of the glycerol into the sample at 20 degrees C, as well as the evolution of distinctamorphous vs. crystalline phases after freezing to -196 degrees C. In the mock cryosurgery example,the iceball edge was clearly visualized, and attempts to determine the temperature within theiceball are discussed. An added benefit of this work is that the density of these frozen samples, anessential property in measurement and modeling of thermal processes, was obtained in comparison toice.

Keywords Biocompatible Materials; Cryopreservation; Crystallography; Liver;Radiographic Image Interpretation, Computer-Assisted

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-304

Abstract Ventricular tachycardia (VT) provokes sudden cardiac death (SCD), which is amajor cause of mortality in developed countries. Implantable cardioverter-defibrillators (ICDs) arean efficient therapy for SCD prevention. In this study we analyze heart rate variability (HRV) indata stored by ICDs. In 29 patients exhibiting VT episodes, the last 1000 normal beat-to-beatintervals are analyzed and compared to an individually acquired control time series (CON). HRVanalysis is performed with standard parameters of time and frequency domain as suggested by the HRVTask Force. For scaling analyses of heart rate time series, the fractal dimension is analysed,applying Higuchi’’s algorithm (HFD). Furthermore, detrended fluctuation analysis (DFA) is performed.None of the standard HRV parameters shows significant differences between CON and VT. Before theonset of VT, the scaling characteristics by means of HFD and DFA are significantly changed.Inconclusion, scaling analysis reveals changes in autonomic heart rate modulation preceding VT.

Keywords Algorithms; Diagnosis, Computer-Assisted; Electrocardiography; Heart Failure,Congestive

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-207

Abstract Hemodynamic forces applied at the apical surface of vascular endothelialcells may be redistributed to and amplified at remote intracellular organelles and protein complexeswhere they are transduced to biochemical signals. In this study we sought to quantify the effectsof cellular material inhomogeneities and discrete attachment points on intracellular stressesresulting from physiological fluid flow. Steady-state shear- and magnetic bead-induced stress,strain, and displacement distributions were determined from finite-element stress analysis of acell-specific, multicomponent elastic continuum model developed from multimodal fluorescence imagesof confluent endothelial cell (EC) monolayers and their nuclei. Focal adhesion locations and areaswere determined from quantitative total internal reflection fluorescence microscopy and verifiedusing green fluorescence protein-focal adhesion kinase (GFP-FAK). The model predicts that shearstress induces small heterogeneous deformations of the endothelial cell cytoplasm on the order of<100 nm. However, strain and stress were amplified 10-100-fold over apical values in and around thehigh-modulus nucleus and near focal adhesions (FAs) and stress distributions depended on flowdirection. The presence of a 0.4 microm glycocalyx was predicted to increase intracellular stressesby approximately 2-fold. The model of magnetic bead twisting rheometry also predicted heterogeneousstress, strain, and displacement fields resulting from material heterogeneities and FAs. Thus, largedifferences in moduli between the nucleus and cytoplasm and the juxtaposition of constrainedregions (e.g. FAs) and unattached regions provide two mechanisms of stress amplification in shearedendothelial cells. Such phenomena may play a role in subcellular localization of earlymechanotransduction events.

Keywords Cell Adhesion; Endothelial Cells; Focal Adhesions; Mechanotransduction,Cellular

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-223

Abstract The tympanic membrane or eardrum of human ear transfers sound waves intomechanical vibration from the external ear canal into the middle ear and cochlea. Mechanicalproperties of the tympanic membrane (TM) play an important role in sound transmission through theear. Although limited resources about linear elastic properties of the TM are available inliterature, there is a lack of measurement or modeling of viscoelastic properties of the TM at lowstress levels. In this study, the uniaxial tensile, stress relaxation, and failure tests wereconducted on fresh human cadaver TM specimens to explore mechanical properties of the TM. Theexperimental results were analyzed using the hyperelastic Ogden model and digital image correlationmethod. The constitutive equation and non-linear elastic properties of the TM were presented byfunctions of the stress and strain at the stress range from 0 to 1 MPa. Viscoelastic properties ofthe TM were described by the stress relaxation function and hysteresis. The results show that theuniaxial tensile test with the aid of digital image correlation analysis is a reliable and usefulapproach for measuring mechanical properties of ear tissues. The data presented in this papercontribute to ear biomechanics in both experimental measurement and theoretical analysis of eartissues.

Keywords Models, Biological; Tympanic Membrane

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-314

Abstract Blunt carotid artery injuries occur in 0.3% of blunt injured patients and maylead to devastating neurological consequences. However, arterial mechanics leading to internallayer subfailure have not been quantified. Twenty-two human carotid artery segments and 18 porcinethoracic aorta segments were opened to expose the intimal side and longitudinally distracted tofailure. Porcine aortas were a geometrically accurate model of human carotid arteries. Internallayer subfailures were identified using videography and correlated with mechanical data.Ninety-three percent (93%) of vessels demonstrated subfailure prior to catastrophic failure. Allsubfailures occurred on the intimal surface. Initial subfailure occurred at 79% of the stress and85% of the strain to catastrophic failure in younger porcine specimens, compared to 44% and 60%,respectively, in older human specimens. In most cases, multiple subfailures occurred prior tocatastrophic failure. Due to limitations in human specimen quality (age, priorstorage), young andfresh porcine aorta specimens are likely a more accurate model of clinical blunt carotid arteryinjuries. Present results indicate that vessels are acutely capable of maintaining physiologicfunction following initial subfailure. Delayed symptomatology commonly associated with bluntarterial injuries is explained by this mechanics-based and experimentally quantified onset ofsubcatastrophic failure.

Keywords Carotid Artery Injuries; Endothelium, Vascular; Models, Cardiovascular;Thoracic Arteries

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-291

Abstract Airway smooth muscle cells exhibit stiffening during contractile activation.This stiffening may be interpreted as a result of the stabilizing influence of the mechanicalprestress stored within the cytoskeleton (CSK). However, in vivo, airway smooth muscle cellscontract while simultaneously experiencing breathing-induced stretching. Excessive stretching ofcells could cause actin-myosin crosslinks, and possibly other cytoskeletal filaments, to break,thereby leading to dissipation of the prestress and inhibition of further cell stiffening. The aimof this study is to investigate the stiffening behavior of individual human airway smooth muscle(HASM) cells exposed to a combination of substrate stretching, contractile activation andrelaxation. We treated cultured HASM cells with either contractile (histamine) or relaxing (DBcAMP)pharmacological agonists and used magnetic cytometry technique to investigate the stiffeningbehavior of these cells during uniform substrate stretching (0-30%). Cells that were not treated, aswell as those treated with histamine, exhibited increasing stiffening during stretching up to 20%of substrate strain, with additional stiffening becoming inhibited for substrate strains of 20-30%.In contrast, in cells treated with DBcAMP, stretching produced moderate but continuous stiffeningwith increasing substrate strain. These results indicate that both active and passive components ofthe prestress contribute to cell stiffening. We also observed that cells permeabilized with saponinexhibited stiffening at low levels (<10%) of substrate stretching, similar to non-permeabilizedcells, but not at high levels (10-30%) of stretching, where stiffening was inhibited. These datasuggest that at low levels of substrate strains the relative contributions of ion channel activationas well as actin and focal adhesion remodeling are less important for stiffening than passivedistension of the CSK. Taken together, our results suggest that both the active and passivecomponents of the cytoskeletal prestress contribute to the stiffening behavior of HASM cells underphysiological conditions, but that at high levels of cellular distensions there is a possibletradeoff between these two components with the contribution from the passive component becomingincreasingly more important.

Keywords Cytoskeleton; Larynx; Mechanotransduction, Cellular; Models, Biological

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-234

Abstract Mechanical conditioning represents a potential means to enhance thebiochemical and biomechanical properties of tissue engineered vascular grafts (TEVGs). A pulsatileflow bioreactor was developed to allow shear and pulsatile stimulation of TEVGs. Physiological 120mmHg/80 mmHg peak-to-trough pressure waveforms can be produced at both fetal and adult heart rates.Flow rates of 2 mL/sec, representative of flow through small diameter blood vessels, can begenerated, resulting in a mean wall shear stress of approximately 6 dynes/cm(2) within the 3 mm IDconstructs. When combined with non-thrombogenic poly(ethylene glycol) (PEG)-based hydrogels, whichhave tunable mechanical properties and tailorable biofunctionality, the bioreactor represents aflexible platform for exploring the impact of controlled biochemical and biomechanical stimuli onvascular graft cells. In the present study, the utility of this combined approach for improving TEVGoutcome was investigated by encapsulating 10T-1/2 mouse smooth muscle progenitor cells withinPEG-based hydrogels containing an adhesive ligand (RGDS) and a collagenase degradable sequence(LGPA). Constructs subjected to 7 weeks of biomechanical conditioning had significantly highercollagen levels and improved moduli relative to those grown under static conditions.

Keywords Bioreactors; Blood Vessel Prosthesis; Blood Vessels; Myocytes, Smooth Muscle

Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-200