Skull Shape Affects Susceptibility to Traumatic Brain Injury

Rapid deformation of brain matter caused by skull acceleration is one of the most significant causes of concussion and severe traumatic brain injury (TBI). Despite substantial research being conducted in this area of study, very little is understood regarding the mechanics of the brain when exposed to rapid acceleration. As a result, the biomechanics of TBI remain ambiguous. In the present study, we apply a new strain estimation algorithm that enables the tracking of strains on the periphery of an image onto data obtained from tagged gel phantom and human MR-images. We use this new method to quantify strain concentrations at the brain-skull interface, and observe the interactions between the brain and the connective tissue that anchors it inside the skull. Our results allow us to noninvasively observe and quantify the biomechanical response of the brain to rapid skull movement. We find that the sub-arachnoid space creates regions of high strain magnitudes due to its anatomical makeup, and that the falx cerebri creates regions of high strain due to its inhibition of brain motion. Additionally, we see that skull shape significantly affects the transmission of strains at the brain-skull interface, and that certain skull shapes create localized concentrations of high strains. Our results imply that skull shape plays an important role in affecting sensitivity to acceleration among individuals, and may increase the likelihood of TBI in the event of an accident

An advanced course on finite element analysis, with application to the stress distribution in teeth

The overall goal of my work is to gain insight into how tooth shape relates to its function. As a step towards this, I undertook an independent study project to further improve my skills on finite element analysis (FEA) this semester, and to combine this into my Master’s thesis project work. Continuing from the previous independent study course, the tooth model was improved to eliminate singularities and a contact surface model was included to simulate contact stress problems. I believe that these series of problems will be useful to my research. This report contains an overview of some literature that I studied, and a summary of several finite element output plots that I found to be particularly instructive

Tailoring of arteriovenous graft‑to‑vein anastomosis angle to attenuate pathological flow fields

Abstract Arteriovenous grafts are routinely placed to facilitate hemodialysis in patients with end stage renal disease. These grafts are conduits between higher pressure arteries and lower pressure veins. The connection on the vein end of the graft, known as the graft-to-vein anastomosis, fails frequently and chronically due to high rates of stenosis and thrombosis. These failures are widely believed to be associated with pathologically high and low flow shear strain rates at the graft-to-vein anastomosis. We hypothesized that consistent with pipe flow dynamics and prior work exploring vein-to-artery anastomosis angles in arteriovenous fistulas, altering the graft-to-vein anastomosis angle can reduce the incidence of pathological shear rate fields. We tested this via computational fluid dynamic simulations of idealized arteriovenous grafts, using the Bird-Carreau constitutive law for blood. We observed that low graft-to-vein anastomosis angles ( $$40^{\circ }$$ > 40 ∘ ) led to increased incidence of pathologically high shear rates. Optimizations predicted that an intermediate  ( $$\sim 30^\circ$$ ∼ 30 ∘ ) graft-to-anastomosis angle was optimal. Our study demonstrates that graft-to-vein anastomosis angles can significantly impact pathological flow fields, and can be optimized to substantially improve arteriovenous graft patency rates

Multimodal thrombectomy device for treatment of acute deep venous thrombosis

Deep vein thrombosis (DVT) is a potentially deadly medical condition that is costly to treat and impacts thousands of Americans every year. DVT is characterized by the formation of blood clots within the deep venous system of the body. If a DVT dislodges it can lead to venous thromboembolism (VTE) and pulmonary embolism (PE), both of which can lead to significant morbidity or death. Current treatment options for DVT are limited in both effectiveness and safety, in part because the treatment of the DVT cannot be confined to a defined sequestered treatment zone. We therefore developed and tested a novel thrombectomy device that enables the sequesteration of a DVT to a defined treatment zone during fragmentation and evacuation. We observed that, compared to a predicate thrombectomy device, the sequestered approach reduced distal DVT embolization during ex vivo thrombectomy. The sequestered approach also facilitated isovolumetric infusion and suction that enabled clearance of the sequestered treatment zone without significantly impacting vein wall diameter. Results suggest that our novel device using sequestered therapy holds promise for the treatment of high risk large-volume DVTs

An approach to quantifying 3D responses of cells to extreme strain

The tissues of hollow organs can routinely stretch up to 2.5 times their length. Although significant pathology can arise if relatively large stretches are sustained, the responses of cells are not known at these levels of sustained strain. A key challenge is presenting cells with a realistic and well-defined three-dimensional (3D) culture environment that can sustain such strains. Here, we describe an in vitro system called microscale, magnetically-actuated synthetic tissues (micro-MASTs) to quantify these responses for cells within a 3D hydrogel matrix. Cellular strain-threshold and saturation behaviors were observed in hydrogel matrix, including strain-dependent proliferation, spreading, polarization, and differentiation, and matrix adhesion retained at strains sufficient for apoptosis. More broadly, the system shows promise for defining and controlling the effects of mechanical environment upon a broad range of cells

Confidence Intervals for Concentration and Brightness from Fluorescence Fluctuation Measurements

AbstractThe theory of photon count histogram (PCH) analysis describes the distribution of fluorescence fluctuation amplitudes due to populations of fluorophores diffusing through a focused laser beam and provides a rigorous framework through which the brightnesses and concentrations of the fluorophores can be determined. In practice, however, the brightnesses and concentrations of only a few components can be identified. Brightnesses and concentrations are determined by a nonlinear least-squares fit of a theoretical model to the experimental PCH derived from a record of fluorescence intensity fluctuations. The χ2 hypersurface in the neighborhood of the optimum parameter set can have varying degrees of curvature, due to the intrinsic curvature of the model, the specific parameter values of the system under study, and the relative noise in the data. Because of this varying curvature, parameters estimated from the least-squares analysis have varying degrees of uncertainty associated with them. There are several methods for assigning confidence intervals to the parameters, but these methods have different efficacies for PCH data. Here, we evaluate several approaches to confidence interval estimation for PCH data, including asymptotic standard error, likelihood joint-confidence region, likelihood confidence intervals, skew-corrected and accelerated bootstrap (BCa), and Monte Carlo residual resampling methods. We study these with a model two-dimensional membrane system for simplicity, but the principles are applicable as well to fluorophores diffusing in three-dimensional solution. Using simulated fluorescence fluctuation data, we find the BCa method to be particularly well-suited for estimating confidence intervals in PCH analysis, and several other methods to be less so. Using the BCa method and additional simulated fluctuation data, we find that confidence intervals can be reduced dramatically for a specific non-Gaussian beam profile

BioPen: direct writing of functional materials at the point of care

Rapid and precise patterning of functional biomaterials is desirable for point-of-care (POC) tissue engineering and diagnostics. However, existing technologies such as dip-pen nanolithography and inkjet printing are currently unsuitable for POC applications due to issues of cost and portability. Here, we report the development of ‘BioPen', a portable tool for continuous, defined and scalable deposition of functional materials with micrometer spatial resolution and nanolitre volumetric resolution. BioPen is based upon the ballpoint pen but with multiple “ink sources” (functional material solutions) and with an apparatus that can be optimized for writing living cells, proteins, nucleic acids, etc. We demonstrate POC detection of human immunodeficiency virus type 1 (HIV-1) nucleic acid by writing on paper with BioPen using “ink” consisting of nucleic acid probes and nucleic acid-modified gold nanoparticles. We also demonstrate POC tissue engineering by writing a continuous pattern of living, functional, interconnected cells with a defined extracellular environment. Because it is simple, accurate, inexpensive and portable, BioPen has broad potential for POC detection of diagnostic biomarkers, and for POC engineering of tissues for a range of healing applications