Showing papers in "Annals of Biomedical Engineering in 2012"
TL;DR: The mechanisms of action of LLLT at a cellular and at a tissular level are covered and the various light sources and principles of dosimetry that are employed in clinical practice are summarized.
Abstract: Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term “low level laser therapy” or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.
1,055 citations
TL;DR: Characterizing the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects provides critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention techniques.
Abstract: Recent research has suggested a possible link between sports-related concussions and neurodegenerative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been suggested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 sub-concussive and 57 concussive head impacts. The average sub-concussive impact had a rotational acceleration of 1230 rad/s2 and a rotational velocity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention techniques.
434 citations
TL;DR: A novel Laplace–Dirichlet Rule-Based (LDRB) algorithm is presented to perform this task with speed, precision, and high usability and convincingly show that the LDRB algorithm is a robust alternative to DTI for assigning fiber orientation to computational heart models.
Abstract: Electrical waves traveling throughout the myocardium elicit muscle contractions responsible for pumping blood throughout the body. The shape and direction of these waves depend on the spatial arrangement of ventricular myocytes, termed fiber orientation. In computational studies simulating electrical wave propagation or mechanical contraction in the heart, accurately representing fiber orientation is critical so that model predictions corroborate with experimental data. Typically, fiber orientation is assigned to heart models based on Diffusion Tensor Imaging (DTI) data, yet few alternative methodologies exist if DTI data is noisy or absent. Here we present a novel Laplace–Dirichlet Rule-Based (LDRB) algorithm to perform this task with speed, precision, and high usability. We demonstrate the application of the LDRB algorithm in an image-based computational model of the canine ventricles. Simulations of electrical activation in this model are compared to those in the same geometrical model but with DTI-derived fiber orientation. The results demonstrate that activation patterns from simulations with LDRB and DTI-derived fiber orientations are nearly indistinguishable, with relative differences ≤6%, absolute mean differences in activation times ≤3.15 ms, and positive correlations ≥0.99. These results convincingly show that the LDRB algorithm is a robust alternative to DTI for assigning fiber orientation to computational heart models.
427 citations
TL;DR: Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies.
Abstract: Photoacoustic imaging is a biomedical imaging modality that provides functional information, and, with the help of exogenous contrast agents, cellular and molecular signatures of tissue. In this article, we review the biomedical applications of photoacoustic imaging assisted with exogenous contrast agents. Dyes, noble metal nanoparticles, and other constructs are contrast agents which absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic response. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications ranging from detection of cancer cells, sentinel lymph nodes, and micrometastasis to angiogenesis to characterization of atherosclerotic plaques. Multi-functional agents have also been developed, which can carry drugs or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents were used to guide and monitor the therapeutic procedures. Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies.
356 citations
TL;DR: Although less frequent, youth football can produce high head accelerations in the range of concussion causing impacts measured in adults, and youth football practices should be modified to eliminate high impact drills that do not replicate the game situations.
Abstract: The head impact exposure for athletes involved in football at the college and high school levels has been well documented; however, the head impact exposure of the youth population involved with football has yet to be investigated, despite its dramatically larger population. The objective of this study was to investigate the head impact exposure in youth football. Impacts were monitored using a custom 12 accelerometer array equipped inside the helmets of seven players aged 7–8 years old during each game and practice for an entire season. A total of 748 impacts were collected from the 7 participating players during the season, with an average of 107 impacts per player. Linear accelerations ranged from 10 to 100 g, and the rotational accelerations ranged from 52 to 7694 rad/s2. The majority of the high level impacts occurred during practices, with 29 of the 38 impacts above 40 g occurring in practices. Although less frequent, youth football can produce high head accelerations in the range of concussion causing impacts measured in adults. In order to minimize these most severe head impacts, youth football practices should be modified to eliminate high impact drills that do not replicate the game situations.
236 citations
TL;DR: It is concluded that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange.
Abstract: Endothelial cells are covered with a polysaccharide rich layer more than 400 nm thick, mechanical properties of which limit access of circulating plasma components to endothelial cell membranes. The barrier properties of this endothelial surface layer are deduced from the rate of tracer penetration into the layer and the mechanics of red and white cell movement through capillary microvessels. This review compares the mechanosensor and permeability properties of an inner layer (100-150 nm, close to the endothelial membrane) characterized as a quasi-periodic structure which accounts for key aspects of transvascular exchange and vascular permeability with those of the whole endothelial surface layers. We conclude that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange. The differences between the properties of the whole layer and the inner glycocalyx structures likely reflect dynamic aspects of the endothelial surface layer including tracer binding to specific components, synthesis and degradation of key components, activation of signaling pathways in the endothelial cells when components of the surface layer are lost or degraded, and the spatial distribution of adhesion proteins in microdomains of the endothelial cell membrane.
232 citations
TL;DR: Recently a number of technical advances have been developed to improve the quantitative accuracy and temporal resolution of speckle imaging and this article reviews some of these recent advances and describes several applications of speckingle imaging.
Abstract: Laser speckle contrast imaging (LSCI) has emerged over the past decade as a powerful, yet simple, method for imaging of blood flow dynamics in real time. The rapid adoption of LSCI for physiological studies is due to the relative ease and low cost of building an instrument as well as the ability to quantify blood flow changes with excellent spatial and temporal resolution. Although measurements are limited to superficial tissues with no depth resolution, LSCI has been instrumental in pre-clinical studies of neurological disorders as well as clinical applications including dermatological, neurosurgical and endoscopic studies. Recently a number of technical advances have been developed to improve the quantitative accuracy and temporal resolution of speckle imaging. This article reviews some of these recent advances and describes several applications of speckle imaging.
226 citations
TL;DR: Preliminary results provide preliminary confirmation that model-predicted strain and strain rate in the CC correlate with changes in indices of white matter integrity.
Abstract: On-field monitoring of head impacts, combined with finite element (FE) biomechanical simulation, allow for predictions of regional strain associated with a diagnosed concussion. However, attempts to correlate these predictions with in vivo measures of brain injury have not been published. This article reports an approach to and preliminary results from the correlation of subject-specific FE model-predicted regions of high strain associated with diagnosed concussion and diffusion tensor imaging to assess changes in white matter integrity in the corpus callosum (CC). Ten football and ice hockey players who wore instrumented helmets to record head impacts sustained during play completed high field magnetic resonance imaging preseason and within 10 days of a diagnosed concussion. The Dartmouth Subject-Specific FE Head model was used to generate regional predictions of strain and strain rate following each impact associated with concussion. Maps of change in fractional anisotropy (FA) and median diffusivity (MD) were generated for the CC of each athlete to correlate strain with change in FA and MD. Mean and maximum strain rate correlated with change in FA (Spearman ρ = 0.77, p = 0.01; 0.70, p = 0.031), and there was a similar trend for mean and maximum strain (0.56, p = 0.10; 0.6, p = 0.07), as well as for maximum strain with change in MD (−0.63, p = 0.07). Change in MD correlated with injury-to-imaging interval (ρ = −0.80, p = 0.006) but change in FA did not (ρ = 0.18, p = 0.62). These results provide preliminary confirmation that model-predicted strain and strain rate in the CC correlate with changes in indices of white matter integrity.
223 citations
TL;DR: Results show that the absorption of a given solute into PDMS depends on the hydrophilic/hydrophobic balance defined by its log P value, and quantitatively investigate the relationship between the partition coefficient (log P) of a series of markers routinely used in in vitro cellular assays.
Abstract: Microfluidic devices fabricated using poly(dimethylsiloxane) (PDMS) polymer are routinely used for in vitro cell culture for a wide range of cellular assays. These assays typically involve the incubation of cultured cells with a drug molecule or a fluorescent marker while monitoring a cellular response. The accuracy of these assays depends on achieving a consistent and reproducible concentration of solute molecules in solution. However, hydrophobic therapeutic and fluorescent molecules tend to diffuse into the PDMS walls of the microfluidic devices, which reduce their concentration in solution and consequently affect the accuracy and reliability of these assays. In this paper, we quantitatively investigate the relationship between the partition coefficient (log P) of a series of markers routinely used in in vitro cellular assays including [3H]-dexamethasone, [3H]-diazepam, [14C]-mannitol, [3H]-phenytoin, and rhodamine 6G and their absorption into PDMS microfluidic channels. Our results show that the absorption of a given solute into PDMS depends on the hydrophilic/hydrophobic balance defined by its log P value. Specifically, results demonstrate that molecules with log P less than 2.47 exhibit minimal absorption ( 90%) into PDMS channels. Further investigations showed that TiO2 and glass coatings of PDMS channels reduced the absorption of hydrophobic molecules (log P > 2.62) by 2- and 4.5-folds, respectively.
213 citations
TL;DR: Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.
Abstract: Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1–8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40–60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.
205 citations
TL;DR: Measurements from the two methods of study are correlated and provide a link that can be used to better interpret findings from future study using either technology.
Abstract: Over the last decade, advances in technology have enabled researchers to evaluate concussion biomechanics through measurement of head impacts sustained during play using two primary methods: (1) laboratory reconstruction of open-field head contact, and (2) instrumented helmets. The purpose of this study was to correlate measures of head kinematics recorded by the Head Impact Telemetry (HIT) System (Simbex, NH) with those obtained from a Hybrid III (HIII) anthropometric headform under conditions that mimicked impacts occurring in the NFL. Linear regression analysis was performed to correlate peak linear acceleration, peak rotational acceleration, Gadd Severity Index (GSI), and Head Injury Criterion (HIC(15)) obtained from the instrumented helmet and HIII. The average absolute location error between instrumented helmet impact location and the direction of HIII head linear acceleration were also calculated. The HIT System overestimated Hybrid III peak linear acceleration by 0.9% and underestimated peak rotational acceleration by 6.1% for impact sites and velocities previously identified by the NFL as occurring during play. Acceleration measures for all impacts were correlated; however, linear was higher (r(2) = 0.903) than rotational (r(2) = 0.528) primarily due to lower HIT System rotational acceleration estimates at the frontal facemask test site. Severity measures GSI and HIC were also found to be correlated, albeit less than peak linear acceleration, with the overall difference between the two systems being less than 6.1% for either measure. Mean absolute impact location difference between systems was 31.2 ± 46.3° (approximately 0.038 ± 0.050 m), which was less than the diameter of the impactor surface in the test. In instances of severe helmet deflection (2.54-7.62 cm off the head), the instrumented helmet accurately measured impact location but overpredicted all severity metrics recorded by the HIII. Results from this study indicate that measurements from the two methods of study are correlated and provide a link that can be used to better interpret findings from future study using either technology.
TL;DR: A computational framework for multiscale modeling and simulation of blood flow in coronary artery bypass graft (CABG) patients is presented and it is observed that PV loops do not change significantly after CABG but that both coronary perfusion and local hemodynamic parameters near the anastomosis region change substantially.
Abstract: We present a computational framework for multiscale modeling and simulation of blood flow in coronary artery bypass graft (CABG) patients. Using this framework, only CT and non-invasive clinical measurements are required without the need to assume pressure and/or flow waveforms in the coronaries and we can capture global circulatory dynamics. We demonstrate this methodology in a case study of a patient with multiple CABGs. A patient-specific model of the blood vessels is constructed from CT image data to include the aorta, aortic branch vessels (brachiocephalic artery and carotids), the coronary arteries and multiple bypass grafts. The rest of the circulatory system is modeled using a lumped parameter network (LPN) 0 dimensional (0D) system comprised of resistances, capacitors (compliance), inductors (inertance), elastance and diodes (valves) that are tuned to match patient-specific clinical data. A finite element solver is used to compute blood flow and pressure in the 3D (3 dimensional) model, and this solver is implicitly coupled to the 0D LPN code at all inlets and outlets. By systematically parameterizing the graft geometry, we evaluate the influence of graft shape on the local hemodynamics, and global circulatory dynamics. Virtual manipulation of graft geometry is automated using Bezier splines and control points along the pathlines. Using this framework, we quantify wall shear stress, wall shear stress gradients and oscillatory shear index for different surgical geometries. We also compare pressures, flow rates and ventricular pressure–volume loops pre- and post-bypass graft surgery. We observe that PV loops do not change significantly after CABG but that both coronary perfusion and local hemodynamic parameters near the anastomosis region change substantially. Implications for future patient-specific optimization of CABG are discussed.
TL;DR: An overview of time-resolved (lifetime) fluorescence techniques used in biomedical diagnostics and evaluates whether intrinsic fluorescence signals provide useful contrast for the diagnosis of human diseases including cancer, skin and eye diseases, and atherosclerotic cardiovascular disease.
Abstract: This article presents an overview of time-resolved (lifetime) fluorescence techniques used in biomedical diagnostics In particular, we review the development of time-resolved fluorescence spectroscopy (TRFS) and fluorescence lifetime imaging (FLIM) instrumentation and associated methodologies which allow in vivo characterization and diagnosis of biological tissues Emphasis is placed on the translational research potential of these techniques and on evaluating whether intrinsic fluorescence signals provide useful contrast for the diagnosis of human diseases including cancer (gastrointestinal tract, lung, head and neck, and brain), skin and eye diseases, and atherosclerotic cardiovascular disease
TL;DR: Recent attempts to extend tissue-engineered platforms toward simulating organ structure and function are surveyed, and microtechnologies that exploit phenomena associated with compartmentalization to create model culture systems that better represent the in vivo organ microenvironment are discussed.
Abstract: Advances in microengineering technologies have enabled a variety of insights into biomedical sciences that would not have been possible with conventional techniques. Engineering microenvironments that simulate in vivo organ systems may provide critical insight into the cellular basis for pathophysiologies, development, and homeostasis in various organs, while curtailing the high experimental costs and complexities associated with in vivo studies. In this article, we aim to survey recent attempts to extend tissue-engineered platforms toward simulating organ structure and function, and discuss the various approaches and technologies utilized in these systems. We specifically focus on microtechnologies that exploit phenomena associated with compartmentalization to create model culture systems that better represent the in vivo organ microenvironment.
TL;DR: Correlation analyses were performed between the proposed criteria and FE-based brain injury predictors such as Cumulative Strain Damage Measure (CSDM), which is defined as the percent volume of the brain that exceeds a specified first principal strain threshold, proposed to predict Diffuse Axonal Injury (DAI).
Abstract: Although Head Injury Criterion (HIC) is an effective criterion for head injuries caused by linear acceleration such as skull fractures, no criteria for head injuries caused by rotational kinematics has been accepted as effective so far. This study proposed two criteria based on angular accelerations for Traumatic Brain Injury (TBI), which we call Rotational Injury Criterion (RIC) and Power Rotational Head Injury Criterion (PRHIC). Concussive and non-concussive head acceleration data obtained from football head impacts were utilized to develop new injury criteria. A well-validated human brain Finite Element (FE) model was employed to find out effective injury criteria for TBI. Correlation analyses were performed between the proposed criteria and FE-based brain injury predictors such as Cumulative Strain Damage Measure (CSDM), which is defined as the percent volume of the brain that exceeds a specified first principal strain threshold, proposed to predict Diffuse Axonal Injury (DAI) which is one of TBI. The RIC was significantly correlated with the CSDMs with the strain thresholds of less than 15% (R > 0.89), which might predict mild TBI. In addition, PRHIC was also strongly correlated with the CSDMs with the strain thresholds equal to or greater than 20% (R > 0.90), which might predict more severe TBI.
TL;DR: The preponderance of the evidence suggests that blast TBI from direct blast exposure occurs on the modern battlefield, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold.
Abstract: Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is appropriate between species, many reported rodent blast TBI experiments using air shock tubes have blast overpressure conditions that are similar to human long-duration nuclear blasts, not high explosive blasts.
TL;DR: This review focuses on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue.
Abstract: Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality.
TL;DR: Repetitive subconcussive head impacts over a single season do not appear to result in short-term neurologic impairment, but these relationships should be further investigated for a potential dose–response over a player’s career.
Abstract: Concussions sustained during college and professional football careers have been associated with both acute and chronic neurologic impairment. The contribution of subconcussive impacts to this impairment has not been adequately studied. Therefore, we investigated the relationship between subconcussive impacts and concussion history on clinical measures of neurologic function. Forty-six collegiate football players completed five clinical measures of neurologic function commonly employed in the evaluation of concussion before and after a single season. These tests included the Automated Neuropsychological Assessment Metrics, Sensory Organization Test, Standardized Assessment of Concussion, Balance Error Scoring System, and Graded Symptom Checklist. The Head Impact Telemetry (HIT) System recorded head impact data including the frequency, magnitude, and location of impacts. College football players sustain approximately 1,000 subconcussive impacts to the head over the course of a season, but for the most part, do not demonstrate any clinically meaningful changes from preseason to postseason on measures of neurologic function. Changes in performance were mostly independent of prior concussion history, and the total number, magnitude and location of sustained impacts over one season as observed R2 values ranged between 0.30 and 0.35. Repetitive subconcussive head impacts over a single season do not appear to result in short-term neurologic impairment, but these relationships should be further investigated for a potential dose–response over a player’s career.
TL;DR: An automated process is developed to identify the orientation of collagen fibres using inexpensive and relatively simple techniques and it is expected that the results of this study will assist those wishing to model skin, and that the algorithm described will be of benefit to those who wish to evaluate the collagen dispersion of other soft tissues.
Abstract: Collagen fibres play an important role in the mechanical behaviour of many soft tissues. Modelling of such tissues now often incorporates a collagen fibre distribution. However, the availability of accurate structural data has so far lagged behind the progress of anisotropic constitutive modelling. Here, an automated process is developed to identify the orientation of collagen fibres using inexpensive and relatively simple techniques. The method uses established histological techniques and an algorithm implemented in the MATLAB image processing toolbox. It takes an average of 15 s to evaluate one image, compared to several hours if assessed visually. The technique was applied to histological sections of human skin with different Langer line orientations and a definite correlation between the orientation of Langer lines and the preferred orientation of collagen fibres in the dermis \((p<0.001, R^{2}= 0.95)\) was observed. The structural parameters of the Gasser–Ogden–Holzapfel (GOH) model were all successfully evaluated. The mean dispersion factor for the dermis was \(\kappa = 0.1404 \pm 0.0028.\) The constitutive parameters μ, k1 and k2 were evaluated through physically-based, least squares curve-fitting of experimental test data. The values found for μ, k1 and k2 were 0.2014 MPa, 243.6 and 0.1327, respectively. Finally, the above model was implemented in ABAQUS/Standard and a finite element (FE) computation was performed of uniaxial extension tests on human skin. It is expected that the results of this study will assist those wishing to model skin, and that the algorithm described will be of benefit to those who wish to evaluate the collagen dispersion of other soft tissues.
TL;DR: Analysis of data from 37,128 head impacts collected at Virginia Tech during games from 2006 to 2010 demonstrates that simple biomechanical parameters that can be measured by the HIT System possess a high level of power for predicting concussion.
Abstract: For several years, Virginia Tech and other schools have measured the frequency and severity of head impacts sustained by collegiate American football players in real time using the Head Impact Telemetry (HIT) System of helmet-mounted accelerometers. In this study, data from 37,128 head impacts collected at Virginia Tech during games from 2006 to 2010 were analyzed. Peak head acceleration exceeded 100 g in 516 impacts, and the Head Injury Criterion (HIC) exceeded 200 in 468 impacts. Four instrumented players in the dataset sustained a concussion. These data were used to develop risk curves for concussion as a function of peak head acceleration and HIC. The validity of this biomechanical approach was assessed using epidemiological data on concussion incidence from other sources. Two specific aspects of concussion incidence were addressed: the variation by player position, and the frequency of repeat concussions. The HIT System data indicated that linemen sustained the highest overall number of head impacts, while skill positions sustained a higher number of more severe head impacts (peak acceleration > 100 g or HIC > 200). When weighted using injury risk curves, the HIT System data predicted a higher incidence of concussion in skill positions compared to linemen at rates that were in strong agreement with the epidemiological literature (Pearson’s r = 0.72–0.87). The predicted rates of repeat concussions (21–39% over one season and 33–50% over five seasons) were somewhat higher than the ranges reported in the epidemiological literature. These analyses demonstrate that simple biomechanical parameters that can be measured by the HIT System possess a high level of power for predicting concussion.
TL;DR: Gold nanorods, which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application and are also promising theranostic agents, combining both tumor diagnosis and treatment.
Abstract: Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application. These include photothermal therapy, molecular imaging, biosensing, and gene delivery, especially for the treatment of diseased tissues such as cancer. These biomedical applications of GNRs arise from their various useful properties; photothermal (nanoheater) properties, efficient large scale synthesis, easy functionalization, and colloidal stability. In addition, GNRs do not decompose and have an enhanced scattering signal and tunable longitudinal plasmon absorption which allow them to be used as a stable contrast agent. Therefore, GNRs are also promising theranostic agents, combining both tumor diagnosis and treatment. In this review, we discuss the recent progress of in
vitro and in
vivo explorations of the diagnostic and therapeutic applications of GNRs as a component of cancer therapy.
TL;DR: This review provides a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability and discusses how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function.
Abstract: Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.
TL;DR: This work provides a review of the historical developments of confocal imaging in vivo, the evolution of endomicroscope instrumentation, and the medical applications of confOCS, and concludes that technical advances will continue to enable application to less accessible organs and more complex systems in the body.
Abstract: Advances in fiber optic technology and miniaturized optics and mechanics have propelled confocal endomicroscopy into the clinical realm. This high resolution, non-invasive imaging technology provides the ability to microscopically evaluate cellular and sub-cellular features in tissue in vivo by optical sectioning. Because many cancers originate in epithelial tissues accessible by endoscopes, confocal endomicroscopy has been explored to detect regions of possible neoplasia at an earlier stage by imaging morphological features in vivo that are significant in histopathologic evaluation. This technique allows real-time assessment of tissue which may improve diagnostic yield by guiding biopsy. Research and development continues to reduce the overall size of the imaging probe, increase the image acquisition speed, and improve resolution and field of view of confocal endomicroscopes. Technical advances will continue to enable application to less accessible organs and more complex systems in the body. Lateral and axial resolutions down to 0.5 and 3 μm, respectively, field of view as large as 800 × 450 μm, and objective lens and total probe outer diameters down to 0.35 and 1.25 mm, respectively, have been achieved. We provide a review of the historical developments of confocal imaging in vivo, the evolution of endomicroscope instrumentation, and the medical applications of confocal endomicroscopy.
TL;DR: In subject-specific computational hemodynamics models of the human aorta the imposition of BC settings based on non-invasively measured flow rate waveforms influences indicators of abnormal flow to a large extent and a BCs set-up assuring realistic, subject- specific instantaneous flow rate distribution must be applied when BCs such as flow rates are prescribed.
Abstract: The purpose of this study is to investigate how the imposition of personalized, non-invasively measured blood flow rates as boundary conditions (BCs) influences image-based computational hemodynamic studies in the human aorta. We extracted from 4D phase-contrast MRI acquisitions of a healthy human (1) the geometry of the thoracic aorta with supra-aortic arteries and (2) flow rate waveforms at all boundaries. Flow simulations were carried out, and the implications that the imposition of different BC schemes based on the measured flow rates have on wall shear stress (WSS)-based indicators of abnormal flow were analyzed. Our results show that both the flow rate repartition among the multiple outlets of the aorta and the distribution and magnitude of the WSS-based indicators are strongly influenced by the adopted BC strategy. Keeping as reference hemodynamic model the one where the applied BC scheme allowed to obtain a satisfactory agreement between the computed and the measured flow rate waveforms, differences in WSS-based indicators up to 49% were observed when the other BC strategies were applied. In conclusion, we demonstrate that in subject-specific computational hemodynamics models of the human aorta the imposition of BC settings based on non-invasively measured flow rate waveforms influences indicators of abnormal flow to a large extent. Hence, a BCs set-up assuring realistic, subject-specific instantaneous flow rate distribution must be applied when BCs such as flow rates are prescribed.
TL;DR: Lagrangian Coherent Structures and 4D PC-MR enables measurement of vortex ring volume during rapid filling of the LV, and shows additional complexity and asymmetry, related to endocardial trabeculation and papillary muscles.
Abstract: Recent studies suggest that vortex ring formation during left ventricular (LV) rapid filling is an optimized mechanism for blood transport, and that the volume of the vortex ring is an important measure. However, due to lack of quantitative methods, the volume of the vortex ring has not previously been studied. Lagrangian Coherent Structures (LCS) is a new flow analysis method, which enables in vivo quantification of vortex ring volume. Therefore, we aimed to investigate if vortex ring volume in the human LV can be reliably quantified using LCS and magnetic resonance velocity mapping (4D PC-MR). Flow velocities were measured using 4D PC-MR in 9 healthy volunteers and 4 patients with dilated ischemic cardiomyopathy. LV LCS were computed from flow velocities and manually delineated in all subjects. Vortex volume in the healthy volunteers was 51 ± 6% of the LV volume, and 21 ± 5% in the patients. Interobserver variability was −1 ± 13% and interstudy variability was −2 ± 12%. Compared to idealized flow experiments, the vortex rings showed additional complexity and asymmetry, related to endocardial trabeculation and papillary muscles. In conclusion, LCS and 4D PC-MR enables measurement of vortex ring volume during rapid filling of the LV.
TL;DR: It is suggested that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC–EC adhesion, and future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit.
Abstract: The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer has been shown to affect hemodynamics in small blood vessels of the microcirculation, the resistance to flow, and leukocyte (WBC) to EC adhesion. Parallel studies of WBC–EC adhesion in response to chemoattractants and cytokines, and shedding of constituents of the glycocalyx, have suggested a role for activation of extracellular proteases in mediating the dynamics of WBC adhesion in response to inflammatory and ischemic stimuli. Likely candidates among the many proteases present are the matrix metalloproteases (MMPs). Inhibition of MMP activation with sub-antimicrobial doses of doxycycline, or zinc chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant fMLP. Taken together, these studies suggest that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC–EC adhesion. Future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit by further exploration of the mechanics of the glycocalyx in light of protease activation and shear-dependent effects.
TL;DR: This review provides a theoretical discussion of concussion mechanics and examines the current literature on the effects of the number of impacts, impact magnitude, impact distribution, and concussion threshold in high school and collegiate football athletes recorded by the HIT System.
Abstract: Researchers are striving to understand the biomechanics of concussive injury that occur in the context of sport by using a number of methodologies. Animal models, video reconstruction, and helmet-based accelerometers have all been used, but have their limitations. The Head Impact Telemetry (HIT) System permits the real-time in vivo tracking of all impacts that occur on the football field and has been used in both the high school and collegiate setting. This review provides a theoretical discussion of concussion mechanics and examines the current literature on the effects of the number of impacts, impact magnitude, impact distribution, and concussion threshold in high school and collegiate football athletes recorded by the HIT System.
TL;DR: Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth.
Abstract: Site-specific delivery of nanoparticles poses a significant challenge, especially in the brain where the blood-brain barrier prevents the entry of most therapeutic compounds including nanoparticle-based anti-cancer agents. In this context, the use of macrophages as vectors for the delivery of gold-silica nanoshells to infiltrating gliomas will be reviewed in this article. Gold-silica nanoshells are readily phagocytosed by macrophages without any apparent toxic effects, and the results of in vitro studies have demonstrated the migratory potential of nanoshell-loaded macrophages in human glioma spheroids. Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth. Collectively, these findings demonstrate the potential of macrophages as nanoshell delivery vectors for photothermal therapy of gliomas, and they certainly provide the basis for future animal studies.
TL;DR: The developed foot and ankle model was used to investigate the injury tolerance of the ankle joint under brake pedal loading for internally and externally rotated feet and indicated improved biofidelity relative to previous FE models.
Abstract: A finite element (FE) model of the foot and leg was developed to improve understanding of injury mechanisms of the ankle and subtalar joints during vehicle collisions and to aid in the design of injury countermeasures. The FE model was developed based on the reconstructed geometry of a male volunteer close to the anthropometry of a 50th percentile male and a commercial anatomical database. While the forefoot bones were defined as rigid bodies connected by ligament models, the surrounding bones of the ankle and subtalar joints and the leg bones were modeled as deformable structures. The material and structural properties were selected based on a synthesis of current knowledge of the constitutive models for each tissue. The whole foot and leg model was validated in different loading conditions including forefoot impact, axial rotation, dorsiflexion, and combined loadings. Overall results obtained in the model validation indicated improved biofidelity relative to previous FE models. The developed model was used to investigate the injury tolerance of the ankle joint under brake pedal loading for internally and externally rotated feet. Ligament failures were predicted as the main source of injury in this loading condition. A 12% variation of failure moment was observed in the range of axial foot rotations (±15°). The most vulnerable position was the internally rotated (15°) posture among three different foot positions. Furthermore, the present foot and ankle model will be coupled together with other body region FE models into the state-of-art human FE model to be used in the field of automotive safety.
TL;DR: Several theranostic agents and their impact on the development of more effective photothermal therapies for the treatment of cancer are discussed, including hollow gold nanoshells, gold gold-sulfide nanoparticles, gold nanocages, carbon and titanium nanotubes, photothermal-based nanobubbles, polymeric nanoparticles and copper-based nanoparticles.
Abstract: The theranostic potential of several nanostructures has been discussed in the context of photothermal therapies and imaging In the last several decades, the burden of cancer has grown rapidly, making the need for new theranostic approaches vital Lasers have emerged as promising tools in cancer treatment, especially with the advent of photothermal therapies wherein light absorbing dyes or plasmonic gold nanoparticles are used to generate heat and achieve tumor damage Recently, photoabsorbing nanostructures have materialized that can be employed in conjunction with lasers in the near-infrared region in order to enhance both imaging and photothermal effects The incorporation of tunable nanostructures has resulted in improved specificity in cancer treatment Silica-cored gold nanoshells and gold nanorods currently serve as the chief plasmonic structures for photothermal therapy Although gold nanorods and silica-cored gold nanoshells have shown promise as therapeutic agents, over the past few years new nanostructures have emerged that offer comparable and even superior theranostic properties In the present review, several theranostic agents and their impact on the development of more effective photothermal therapies for the treatment of cancer are discussed These agents include hollow gold nanoshells, gold gold-sulfide nanoparticles, gold nanocages, carbon and titanium nanotubes, photothermal-based nanobubbles, polymeric nanoparticles and copper-based nanocrystals