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The ligamentous human lumbar spine is considered as a long and slender column, which can be buckled when subjected to the axial compressive load even less than 100N. However, previous in vivo study showed that the compressive force acting on the spine predicted by intradiscal pressure was exceed 2600N. Meanwhile, recent experiments suggested that, when the compressive force is subjected to the lumbar spine along the spinal curvature (follower load), the lumbar spine may support up to a compressive force of 1200N without buckling while maintaining its flexibility. Since such a follower load is directed tangential to the curved column over the entire length, the lumbar spine subjected to a follower load should experience only pure compressive force components with zero shear force components. It is generally agreed that the ligamentous lumbar spine can be stabilized by applying the muscle forces (MFs) in vivo creating follower compressive loads (FCLs). In previous studies, computational model of the lumbar spine showed the feasibility for spinal muscles to stabilize the lumbar spine via the FCL mechanism, which supports the hypothesis of FCLs as normal physiological loads in the spine in-vivo. In addition, the muscle forces of short intrinsic muscles (SIMs), such as interspinales, intertransversarii, and rotatores may increase the stability of the lumbar spine (i.e., deflection of the spinal column or trunk sway) significantly. However, the mechanical roles of SIMs for spinal stability have not been quantified and understood well. A finite element (FE) model with optimization model of the lumbar spinal system was used in this study. Both models were consisted of 122 pairs of spinal muscle fascicles including 54 SIMs fascicles. The variation of spinal muscle strength was simulated by changing the values of MFCs of long muscles as well as SIMS from zero to 90 N/cm2. Five different MFC conditions of both long muscles and SIMs in the spinal system were investigated in five different postures, which are neutral standing, flexion 40°, extension 5°, left axial rotation 10°, and right lateral bending 30°. The trunk displacement (TD) and joint loads including joint reaction forces (JRFs) and moments (JRMs) predicted from 25 cases of MFC variation were compared in order to investigate the effect of the strength of spinal muscles on the stabilization of the lumbar spine in a given posture. The results showed that small trunk sways (< 2mm) were predicted when MFCs of both long muscles and SIMs were average or higher regardless of the spinal postures. In contrast, no optimum solution or unstable conditions were predicted in many cases of the weakening of the long muscles, especially in flexion and lateral bending postures. Although the FCLs were created in most of the cases regardless of MFC-S when working with strong long muscles, higher joint loads were predicted as a result of weakening of SIMs. In addition, even if the long muscles were strong, absence of SIMs induced spine buckling in some cases of extension and axial rotation postures. The results from this study imply that although the effect of MFCs variation of long muscle and/or SIMs was varied depending the spinal postures, the simultaneous use of both SIMs and long muscles is necessary for stabilization of the spine in any physiological posture with minimum joint loads for maximum safety.

Heart valve disease is estimated to cost over a billion dollars in the Unites States annually and mitral valve disorders account for the largest portion of the disease with treatments involving valve repair and replacement (Iung et. al). It is estimated that an experienced surgeon can effectively repair 95 - 100 percent of mitral valve (MV) disorders but a recent study showed that the average rate of MV repair is 41 percent. The current paradigm in treatments include diagnostic imaging data to see the current state of the patient, empirical data from previous similar cases to evaluate the efficacy of prior treatment and the judgment of the surgeon. Due to immense variability amongst patients in terms of anatomy and physiological conditions, this data alone is insufficient to predict outcomes of treatments. We therefore propose a new paradigm of combining imaging techniques and computational modeling allowing for patient specific modeling of anatomical structures and finite element analysis to predict surgical outcomes. Performing this approach currently requires extensive knowledge of the particular fields and can be difficult to follow for a non-expert. We are thus in the process of developing a user friendly tool which combines these techniques into a single framework which can easily be used by non-experts. The hypothesis of this work is that providing surgeons with prior knowledge of post-repair dynamics of a diseased MV will improve surgical decision making and increase repair rates. This work outlines a framework of user interactive tools for simulating the common techniques used by surgeons to correct mitral regurgitation. This toolset is built as an extension of IA-FEMesh (Grosland et. al) and enables MV leaflet mesh and chordae tendinae mesh generation from point cloud data. It also includes tools for repairing the chordae tendinae, resecting a portion of the valve, applying MV material properties, boundary conditions and exporting these as an Abaqus (.inp) file where the simulation is carried out. The results of these simulations ultimately serve as biomechanical markers for identifying the best surgical method to be used.

One of the most crucial aspects of training first-year surgeons is ensuring that they acquire surgical skills prior to entering the operating room (OR). This study attempts to define a more accurate method of assessing and measuring surgical skills when fixing a hip fracture with a guide wire. The measuring system currently used today, which is widely described as a fairly accurate predictor of fracture fixation failure, can be quite subjective and prone to inaccuracies. This study introduces an alternative method of measurement that quantifies the deviation of guide wire trajectory from an ideal path. We believe that this method is helpful for surgeons to understand the importance of guide wire trajectory, and its application can be extended to both surgical simulation and the OR. Additionally, this study introduces a preliminary experiment that examines the transfer of surgical skills from a hip fracture simulator to a setting that closely resembles the OR. Surgical simulators can be of great benefit to first year surgeons as they look to improve their surgical skills. Surgeons must learn to balance their time appropriately due to the presence of fluoroscopy, which emits radiation, while placing the implant in a satisfactory position. Significant improvements were found in procedural time and the number of fluoroscopic images requested in an OR setting after thirty minutes of simulator use. It is possible that the surgeons were not given enough time to practice on the simulator, so a new experimental design and more subjects will hopefully show more significant improvements after simulator intervention.

Magnetic source MRI (msMRI) has been developed recently for direct detections of neuronal magnetic fields to map brain activity. However, whether MRI can be used for direct detection of neuronal activity is a matter of debate. Controversial theoretical and experimental results have been reported. In this work, theoretical modeling and experimental validation have been presented to demonstrate that the neuronal current signal is in the detectable range and could be detected by MRI. In the theoretical modeling section, we present an improved current-dipole model to compute magnetic field generated by neural firing and to calculate MRI signal changes resulting from the neuronal magnetic field. Neuronal magnetic field were estimated based on a synchronized activity of multiple neurons. Our results show that neuronal magnetic field can potentially generate up to a few percent changes in MRI magnitude signals. Phases of MRI signal tend to be destructively added and are insensitive to neuronal magnetic field in the activated region when the distribution of the activated dendrites is symmetrical. Our modeling implies that direct MRI detection of neuronal activity is possible. In the experimental validation section, a rapid median nerve stimulation paradigm has been used to detect the neuronal activity. The experiments were performed on six normal human participants to investigate the temporal specificity of the effect, as well as inter- and intra-subject reproducibility. Significant activation of contra-lateral primary sensory cortex (S1) was detected 80ms after stimulation onset (corresponding to the P80 evoked potential peak). The 80 ms latency S1 activation was observed over 3 independent sessions for one subject and for all 6 participants. The magnitude of the signal change was 0.2% - 0.3%. Coinciding with our expectations, no S1 activation was found when MRI data acquisitions were targeted at the N20 and P30 peaks because of mutual cancellation of magnetic fields generated by those peaks. The results demonstrated good reproducibility of S1 activations and indicated that the S1 activations most likely originated from neuronal magnetic field rather than hemodynamic response.

Post-traumatic osteoarthritis (PTOA) is a debilitating disorder resulting from trauma to an articulating joint. The condition imposes a significant physical and emotional burden on an individual, with substantial financial implications, as well. The severity of the joint trauma has been shown to correlate highly with the risk of subsequent PTOA development, so treating surgeons have adopted fracture severity assessment methods to aid in their treatment decision-making. However, current systems for classifying the severity of the trauma are highly subjective and have poor reproducibility. This makes it difficult to differentiate PTOA development attributable to the initial injury from that potentially influenced by the chosen treatment. The most common situation in which this problem arises is for an articular fracture, treatment of which involves decisions related to trying to restore the fragmented articular surface. To address these limitations in assessing fracture severity, a CT-based severity metric was previously developed, with the goal of providing an objective, quantifiable measure of initial injury severity. Utilizing fracture mechanics theory, the CT-based severity metric used measures of interfragmentary surface area to infer the amount of energy absorbed during fracture, the amount of comminution in the resulting fracture, and the level of dispersion and displacement of the fracture fragments. Combining these components into a single overall severity score produced a reliable metric for objective assessment of fracture severity. However, this assessment approach did present some practical limitations, which precluded its use in routine clinical care. The greatest limitation was the time required to obtain a severity score. At roughly 8 hours, it was too much time before a surgeon could get a score to assist in treatment planning. Another major challenge in using the severity metric was that its acquisition depended upon the contralateral intact limb being included in the CT scan, for taring purposes. Even though using the intact contralateral would be ideal, obtaining this limb in the CT scan for each patient would be a difficult challenge impeding the implementation of the expedited metric in the routine clinical setting. To address these limitations, an expedited approach for severity assessment has been developed. The expedited approach builds upon the prior fracture mechanics methods, but it utilizes a textural image analysis of CT images from the fractured bone, in lieu of measurement of interfragmentary surface area. The focus of this thesis is the implementation and development of an expedited fracture severity metric that can be used clinically. Such a metric would aid in showing the relative benefits of certain surgical treatments as well as in guiding the surgeon in developing a treatment plan for their patients.

The prevalence of scoliosis in those over age 60 varies from 39%-68%. Common presenting symptoms include back pain, radiculopathy, and progressive deformity. Radiographic characteristics have been previously described that correlate with these symptoms including vertebral spondylolisthesis, endplate obliquity, lumbar hypolordosis, thoracolumbar junction kyphosis and positive sagittal balance. Nevertheless, asymptomatic volunteers present with similar spinal deformities. It is likely that other factors such as age, body habitus, and exercise capacity affect or outweigh the severity of radiographic parameters. The ability to maintain the center of gravity of the body within the cone of economy results from a combination of alignment parameters, but also from neuromuscular control. The aim of this study is to validate a Wii Nintendo balance board evaluation tool for the study of adult spinal deformity, by exploring correlations between the center of pressure sway area and sway path trajectory with clinical outcome scores, patient demographics and radiographic alignment parameters in patients with spinal deformity.

Thrombotic events such as stroke, myocardial infarction, or deep vein thrombosis can be life-threatening; therefore it is important to understand the mechanisms of thrombosis and its correlations with clinical risk factors. It is well known that red blood cells (RBCs) can influence hemostasis and thrombosis by affecting the viscosity and rheological properties of blood. Recent evidence suggests that RBCs may play a more central and active role in some models of experimental thrombosis by interacting directly with the endothelium. It is still unclear, however, if the interaction of RBCs with the endothelial surface is facilitated by other blood components. In order to investigate the interaction of RBCs with endothelium in a defined system in vitro, human umbilical vein endothelial cells (HUVECs) were grown on coverslips and placed in a parallel-plate flow chamber system. Using this system, we tested the hypothesis that RBCs interact directly with ferric chloride-injured endothelium in the absence of other blood components. These experiments demonstrated that RBCs do interact with HUVECs in the flow chamber under both venous and arterial conditions. Using an anti-von Willebrand Factor (VWF) antibody, we demonstrated that the RBC-endothelium interaction is facilitated by VWF in vitro. These findings support a possible active role of RBCs in thrombosis and also demonstrate that RBCs interact with VWF, which was previously unrecognized. Platelets are also known to play an important role in hemostasis and thrombosis, specifically through their interaction with exposed collagen located in the subendothelial matrix that becomes exposed to flowing blood after vascular injury. Platelets may become hyperactive in prothombotic conditions, leading to increased platelet aggregation and thrombotic events. Thrombotic events also increase in the presence of risk factors such as increased age or obesity. Previous data has shown that platelet hydrogen peroxide (H2O2) mediates platelet hyperactivity and that activated platelets from obese mice show increased H2O2 levels. In order to investigate the interactions of platelets with collagen in vitro, the flow chamber system was used with collagen-coated coverslips to study platelet adhesion under arterial and venous conditions. We found that platelets from mice with increased levels of H2O2, due to the genetic deletion of glutathione peroxidase-1 formed larger aggregates than control mice. In preliminary experiments, we observed evidence for increased adhesion and aggregation of platelet from obese mice. These findings confirm the role of H2O2 in platelet hyperactivity and suggest that therapeutic strategies targeted toward lowering platelet H2O2 levels may have the potential to decrease thrombotic complications associated with certain prothrombotic disease states.

Cancer metastasis, or the formation of a secondary tumor at a site distant from the primary tumor, is known to be an inefficient process. Historically, it was believed that the shear stresses and forces experienced by cancer cells traveling through the circulatory system are major limiting factors to their metastatic potential and viability. High levels of fluid shear stress are known to be capable of destroying tumor cells. However, more recent research has shown that cancer cells survive migration through the circulatory system and extravasation into distant tissues with a high degree of efficiency, indicating that hemodynamic forces are not primarily responsible for metastatic cancer cell death. A current subject of investigation is the biomechanical effect of fluid shear stress on cancer cells – how do cancer cells react to the fluidic forces and stresses they experience in circulation? This study focused on quantifying the elastic modulus and rupture behavior of prostate cancer and prostate epithelial cells, with and without exposure to fluid shear stress. Micropipette aspiration was the means of inducing deformation and rupture of the cell membrane. Images obtained through micropipette aspiration were analyzed to calculate elastic modulus and to quantify local stresses along the aspirated cell membrane. An axisymmetric stress model of the aspirated cell membrane was solved using MATLAB; the trends for direction and relative magnitude of stresses were confirmed by an Abaqus finite element model. Results of the micropipette aspiration included statistically significant differences in elastic modulus and rupture pressure between experimental groups. The elastic modulus of epithelial cells exposed to shear stress was significantly higher than that of the cancer cell groups, both exposed and unexposed to shear stress. There was no difference in elastic modulus between cancer cells exposed to shear stress and unexposed to shear stress. This is contrary to the findings of a previous study; prostate cancer cells have been observed to stiffen after exposure to shear stress. It has also been well documented that epithelial cells exhibit higher elastic moduli than cancer cells; however, no difference was observed in this study in the comparison of elastic moduli of cancer and epithelial cells that were unexposed to shear stress. The rupture pressure of the cancer cells unexposed to shear stress was significantly lower than any other group. This suggests a strengthening reaction of the cancer cell membrane in response to shear stress exposure. This effect was observed to be transient; the increase in rupture pressure disappeared by an hour after the shear stress exposure. The epithelial cells did not exhibit any change in rupture pressure after exposure to shear stress. There was no correlation between elastic modulus and rupture pressure; the stiffness of the cells did not indicate how likely they were to rupture. The MATLAB and Abaqus models agreed well for trends of principal stresses and von Mises stress. The MATLAB model was quite sensitive to the curvature of the spline fitted to the membrane edge, resulting in irregular patterns and some extreme values of stress and making the results difficult to interpret. The maximum stress did tend to increase with increased aspiration pressure. The location of the maximum stress along the membrane did not reliably correspond to the location of rupture during micropipette aspiration. This model may be improved by automating the process of fitting a spline to the edge of the membrane to reduce user error in plotting individual points. Further studies to characterize the effects of fluid shear stress on cancer cell mechanics will be useful to confirm differences in elastic modulus and rupture pressure and to investigate the effect of time, temperature, cancer cell line, culture medium, and other variables on cancer cell properties.

In this project we, for the first time, integrated microfluidics with thermo-plasmonics. While microfluidics is a popular platform allowing experiments with small volumes of fluid, thermo-plasmonics can be used for powerful particle manipulation including capturing, mixing, filtering and projection. Combined, these two techniques give us an opportunity to work with numerous complex fluids containing particles, cells, and micro-beads. Here we designed, developed and tested several devices demonstrating various aspects of this exciting hybrid technology. This required use of soft lithography, metal deposition, 3D printing, oxygen plasma treatment and several other surface modification techniques. Additional challenges were in the fabrication of a multi-layer chip with several types of surfaces binding at several interfaces. The detailed design optimization was conducted, and many characteristics of the microfluidic channel were varied. After that, optimal flow patterns were determined using high-quality syringe pumps. An experiment with the simultaneous flow of two colored solutions through the same microfluidic chip demonstrated controlled laminar flow with minimal mixing. Next, thermo-plasmonic experiments were conducted in optimized micro-fluidic channels. Efficient capturing of microbeads were demonstrated using low power green laser with a wavelength 532 nm. In future, these experiments have many important applications including separation of bacteria from blood on a microfluidic chip. This might help with treatment of sepsis, analysis of blood pathogens and better prescription of antibiotics.