Force is required to prepare the bone and achieve the initial press fit for an uncemented hip implant during Total Hip Arthroplasty (THA) surgery. In some situations, this force may cause of an intra-operative femoral fracture resulting in an unstable implant, subsidence, and pain for the patient. Many of the less extensive fractures can be repaired with cerclage wire or cables. This study aimed to evaluate the ability of double loop cerclage wire(s) to restore the stability of the implant-bone interface after a simulated intra-operative fracture. Nine femora from euthanized canine were harvested for in vitro testing. The femora were prepared for implantation of an uncemented femoral stem (BFX⢠series, BioMedtrix, Boonton, NJ). They were then potted and mounted in a materials testing machine (MTS 858 Mini Bionix II, Eden Prairie, MN). The implant was driven to a clinically appropriate height, struck with 3 impacts (simulating seating hammer blows), and then the stem loaded to failure. Once a fracture occurred, the implant was extracted, the femur was repaired with appropriate cerclage, re-broached, and re-implanted. The repaired specimen was then tested in the same fashion as the intact bone. During loading, the displacement of the implant relative to the bone was measured using a linearly variable differential transformer LVDT. The force to initiate subsidence, the peak force at failure, and the peak subsidence distance were compared between intact (pre-fracture) and repaired (post-fracture) specimens using ANOVA with blocking by specimen. The wired specimens demonstrated a higher force to initiate subsidence than the intact specimens (2378.8N ± 656.9N c.f. 1705.1N ± 584.5N; p= 0.0019). The wired specimens also sustained a higher peak force at failure than the intact specimens (3309.0N ± 609.14N c.f. 2276.3N ± 855.6N; p=0.0022). Furthermore, the wired specimens did not subside a significantly greater amount than the intact specimens (Intact: 3.90mm, SD=2.09mm; Wired: 6.71mm, SD=3.66mm; p-value = 0.0600). Cerclage wiring of intra-operative femoral fractures was able to restore the integrity of the femur and enable a stable implant-bone interface to be achieved.

To improve the surface properties of biomaterials, the effects of changes in surface chemistry and morphology of polyethylene terephthalate (PET) films treated with atmospheric pressure plasma were investigated as a function of cellular growth, proliferation, and adhesion. PET films were subjected to helium and helium/oxygen gas plasmas. The contact angle of the treated films decreased due to plasma etching and possible scission indicating that the surfaces become more hydrophilic. Atomic force microscopy results had a large standard error, however the surface visually showed changes in surface micro and nanoscale roughness corresponding to treatment duration. Keratinocytes were plated on the day of plasma treatment and two and five days after plasma treatment and tested half a day, one, two, three, and six days after plating. The same methodology of plating and testing was also applied to hepatocytes. Cell growth, proliferation, and adhesion were characterized via a fluorescent probe based assay and were correlated with surface chemical and nanostructural features. Both the helium and helium/oxygen plasma-treated PET had little or no effect on cell behavior for both keratinocytes and hepatocytes. The nanoscale surface changes due to the plasma surface treatment are believed to be masked by the protein adherence in the media on the surface of the PET.

As a result of the growing costs of healthcare technology, there is an increasing need for medical diagnostic tools that provide accurate information in a portable, low-cost platform. A microfluidic device using on-chip passive pumping was characterized for use as a particle counter. A detection circuit interfaced with electrodes in the microfluidic chip to provide an excitation signal and to detect electrical activity. Flow occurred due to a Young-Laplace pressure gradient between a 1.2 mm diameter inlet and a 4 mm diameter reservoir when 0.5 μL fluid droplets were applied to the inlet using a micropipette. Polystyrene particles were enumerated using the resistive pulse technique, in which particles can be detected based on the difference in particle conductivity from that of the surrounding medium. Particles counted using the passive flow method demonstrated mean particle counts that were within 13% of those detected using a syringe pump, while all pumping methods displayed particle counts that were within 16% of the count obtained using a hemacytometer. Three different sample loading patterns were compared; the methods varied only in the order of sample and wash fluid administration. Zero, one, or two wash droplets were loaded after the first of two sample droplets. No statistical difference was detected in the mean particle counts for all loading patterns using the passive method (p > 0.05). This passive pumping method is easily implemented using only a micropipette, thus reducing the cost and complexity of particle enumeration, and the method can be implemented in a point-of-care (POC) device for a highly portable, cost-effective particle counter. These methods obtained particle counts that were also consistent with syringe pumping (p > 0.05).

The initial torsional stability of a cementless total hip arthroplasty (THA) is one of the key factors in determining the biological fixation of the implant. The success of a cementless hip replacement relies on the quantity and quality of bone ingrowth that occurs. This study looked at the effects of femoral neck resection level on the initial torsional stability of cementless THA in the canine population. Twenty paired cadaver femurs were collected from dogs and implanted with canine cementless hip stems. One femur from each pair was prepared with a neck cut with its medial aspect located at the proximal aspect of the lesser trochanter (low neck cut) and the other with a neck cut with its proximo-lateral aspect at the ossum collis femoris isthmus of the greater trochanter and femoral neck (high neck cut). The specimens were then subjected to cyclic torque loads in the caudal direction (Amplitude: -0.1 N-m to set torque) at four torque levels (1 N-m, 2 N-m, 4 N-m, and 6 N-m) and the torsional displacement, axial subsidence, and strain were all recorded. A paired statistical analysis was completed so that specimens from the same dogs could be compared to each other. The low neck cut group was found to have significantly less micromotion than the high neck cut group during the 1 N-m and 4 N-m torque tests (p = 0.02 for both). Because the high neck cut specimens tended to have more micromotion they may be apt to have lower quality bone ingrowth. A significant difference was not found between the torsional displacements of the two groups. The high neck cut specimens were found to have significantly (p = 0.02) more implant rotation at 1.6 N-m of torque, however the average difference was only about 0.22 degrees which most likely does not indicate a clinically significant difference. No statistical difference was found between the axial subsidence of the high and low neck cut specimens other than at the 6 N-m level (p = 0.02). At 6 N-m the stems in the low neck cut specimens had an average upward movement of 255 +/- 310 um while the stems in the high neck cuts moved in the opposite direction and had an average downward movement of 280 +/- 695 um. The low neck specimens were found to have significantly more canal fill and implant impaction than the high neck cut specimens. This suggests that surgeons need to be mindful that they may not insert stems as deeply in femurs prepared with high neck cuts as they do in femurs with low neck cuts. This study was not able to show that one neck cut level was superior to the other, however the data indicate that the low neck cut group had slightly better stability based on having less micromotion at 1 N-m and 4 N-m and less at rotation at 1.6 N-m.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2006. / Title from title screen (site viewed on Feb. 5, 2007). PDF text: xxi, 185 p. : ill. (some col.) UMI publication number: AAT 3216412. Includes bibliographical references. Also available in microfilm and microfiche format.

<p>Breast cancer is one of the leading causes of death every year in the United States for women. Breast conserving surgery (BCS) is one treatment option for these patients where achieving tumor-free surgical margins is desired to avoid local recurrence [1, 2]. Unfortunately, as many as 17.7-72% of patients undergoing BCS require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [3-11]. Histopathology is the current gold standard for determining surgical margin status; however, given the large volumes of resected breast tissue it is not feasible to section the entire specimen. High re-excision rates and limited histopathological sampling of the tissue represent a significant unmet clinical need for margin assessment for both the surgeon and pathologist. Quantitative diffuse reflectance (DR) spectral imaging has been shown to be a promising tool for interrogating tumor margins but patient and surgical factors have to be accounted for in order to fully exploit the discriminatory capability of the technology. The objective of this work was to characterize an instrument for margin assessment and to evaluate the effects of inter-patient variability and surgical and excisional factors on quantitative tissue optical properties, to devise strategies to exploit optical contrast for the detection of positive (<2mm) tumor margins. In addition, the performance of the spectral imaging platform was evaluated.</p><p>The DR spectral imaging device utilized in these studies consisted of a Xenon lamp, a multi-channel imaging fiber-optic probe, an imaging spectrograph, and a 2D charge-coupled device (CCD) [12]. The instrument was found to extract quantitative optical parameters related to tissue micro-morphology with <15% error. Cross-talk at the tissue surface was <1% when the spacing between adjacent channels was 10mm and the sensing depth of each channel was found to be 0.5-2.2mm, an appropriate depth for identifying close and positive tumor margins. Reproducibility of the imaging protocol was best when the probe was interfaced with lumpectomy specimens from the side; this methodology was maintained for all measurements from lumpectomies in this dissertation.</p><p>DR spectral images were acquired from lumpectomy margins and converted into composition maps of quantitative optical parameters. Mammographic breast density was found to have the greatest impact on the optical data with &#946;-carotene concentration ([&#946;-carotene]) and the ratio of [&#946;-carotene] to the wavelength-averaged reduced scattering coefficient from 450-600nm (<&#956;s'>) being significantly higher in the negative margins of high-density patients (p=0.017 and p=0.038, respectively). We originally hypothesized that increased [&#946;-carotene] would be associated with an increase in fat; however the significant increase in [&#946;-carotene] cannot be attributed to differences in the percentage of adipose tissue since low-density patients should theoretically have higher percentages of this tissue type. Hematoxylin and eosin analysis of the adipose sites (n=25) showed increased [&#946;-carotene] (p=0.066), increased adipocyte density (p=0.034), and smaller adipocyte sizes (p=0.051) in the adipose tissues (where &#946;-carotene is stored) of high-density patients. This analysis suggests that increased [&#946;-carotene] is associated with smaller adipocytes and that high-density breasts overall have smaller adipocytes, thus affecting optical contrast. This increase in [&#946;-carotene] actually served to increase contrast between negative and positive margins which resulted in better classification accuracy in the high-density patients with a conditional inference tree model (77% in low-density and 80% in high-density). </p><p>If the purpose of the spectroscopy tool is to provide a differential diagnosis of benign versus malignant tissue, there must be an understanding of how excision of the tissue affects the optical properties over time, and how differences in surgical techniques affect optical properties. DR spectra were acquired 17±4 minutes post-excision from 12 incised mastectomies and from the surface of 10 lumpectomies 7±3 minutes post-excision. A linear longitudinal model was used to fit the data and obtain a rate of change for the tissue parameters. In lumpectomies, [&#946;-carotene], <&#956;s'>, and [&#946;-carotene]/<&#956;s'> had the lowest percent change (<14%) over 30 minutes; total hemoglobin concentration ([THb]) and [THb]/<&#956;s'> had higher percent changes (>40%) over 30 minutes; hemoglobin saturation (HbSat) showed non-linear changes making it a poor variable for ex vivo margin assessment; and Lymphazurin^TM concentration (denoted as [Lymphazurin^TM]) changed more than 200% in 30 minutes. Although the percent error in [Lymphazurin^TM] was high, all other tissue parameters could be quantified with <3.3% error even when Lymphazurin^TM was 80&#956;M. No significant difference was found between benign and malignant rates of change, and baseline values were not significantly correlated with elapsed time post-excision. Initial values from benign non-cauterized mastectomy (n=13) and cauterized lumpectomy (n=59) sites were compared to assess the effect of cautery. [THb] was the only parameter that was significantly higher in the cauterized lumpectomies (p=0.013) compared to non-cauterized mastectomies. </p><p>The work in this dissertation shows the feasibility of using an optical device for margin assessment and that [&#946;-carotene] and [&#946;-carotene]/<&#956;s'> emerge as important variables for differentiating negative and close/positive margins. These two parameters were likely most important since they were least affected by kinetics, cautery, and the presence of Lymphazurin^TM.</p> / Dissertation

Infrared neural stimulation (INS) uses pulsed infrared light to directly stimulate neural tissue with high spatiotemporal precision and is well documented for peripheral nerve applications; however, prior to this dissertation, INS had not been demonstrated for the central nervous system. This dissertation presents the first successful application of INS in the central nervous system and increases our understanding the effects of pulsed infrared light irradiation on cellular dynamics in the brain. Pulsed infrared light is shown to evoke both excitatory and inhibitory neural activity, and evokes robust optical intrinsic signals indicating multiple cellular mechanisms are activated by INS. Optical imaging of calcium signals evoked by INS identified astrocyte sensitivity to pulsed infrared light confirming that both neurons and astrocytes are stimulated. Application of INS in non-human primate visual cortex demonstrated that pulsed infrared light evokes excitatory neural activity and modulates visually evoked signals, identifying the potential of INS to encode functionally relevant signals into cortex. Overall, these results establish INS as neurostimulation modality for use in the brain, and this dissertation provides the necessary foundation to further develop INS for use in the central nervous system in both research and clinical applications.

Reading is a complex cognitive behavior, which relies on the incorporation of a network of brain regions. White matter is the information transfer pathway between distant brain regions, and thus plays an important role in mediating reading ability. Diffusion Tensor Imaging (DTI) is an MR technique to characterize white matter microstructure by probing the propensity of water molecules¡¯ diffusion in in vivo tissues. This dissertation seeks to investigate the reading network in the brain using diffusion MRI. The first part of the dissertation studies the cortical network with a focus on the putative visual word form area (VWFA), which is reproducibly found to be selectively recruited by visual orthographic conversion. We studied the structural connectivity patterns of the VWF-system in children with typically developing (TD) reading ability and with reading difficulty (RD). We found that the architecture of the VWFA connectivity is fundamentally different between TD and RD groups, with TD showing greater connectivity to linguistic regions than RD, and RD showing greater connectivity to visual regions than TD. The second part of the dissertation studies subcortical-cortical network, with a focus on the thalamus, the way-station of information transfer in white matter. Abnormal thalamo-cortical connectivity was found in the RD group in sensorimotor, orbital frontal and insula cortices. These results suggest that the thalamus plays a key role in reading behavior by mediating the functions of task specific cortical regions. Despite the valuable information DTI can provide, it suffers from fundamental limitations, especially when multiple fiber bundles are present. To address this problem, the third part of the dissertation proposes a new method to study complex white matter structures. It improves the current spherical deconvolution method by relaxing the assumption that all fiber bundles share the same response kernel. The in vivo experiments show that this Multiple Kernel Spherical Deconvolution (MKSD) approach can identify crossing fiber bundles and simultaneously provide an estimate of the diffusion properties intrinsic to each fiber bundle.

A fast approach to reconstruct transmit RF field (|B1+|) maps in high field parallel Magnetic Resonance Imaging is presented in this thesis. First the concepts of parallel imaging reconstruction and the Bloch-Siegert (BS) |B1+| mapping method are introduced. Then we present the idea to accelerate BS field mapping based on the fact that the |B1+|-to-phase encoding pulse for each transmit coil and off-resonance frequency applies a unique phase shift to the same underlying image. This enables joint reconstruction of all images in a BS acquisition from an augmented set of virtual receive coils. Simulations are shown to produce accurate |B1+| maps at high acceleration factors for both Cartesian and Non-Cartesian sampling. Phantom and in vivo experiments confirm the simulation results and endorse the proposed approach. It is also shown that reconstruction accuracy can be improved using disjoint sampling patterns between acquisitions. Noise performance analysis in simulation demonstrates that disjoint sampling produces less noise amplification when compared to same sampling across all the coils. The approach is general in that it can be applied using any auto-calibrated multi coil image reconstruction method.

Clinically compatible ultra-short echo time (UTE) imaging sequences for quantitative T2-based bound and pore water imaging in bone were implemented and validated on a 3T human scanner and a 4.7T small bore system. Pore water images were generated by selectively saturating bound water signals with a T2-selective double adiabatic inversion pulse. Bound water images were generated by nulling the pore water signals with a T2-selective adiabatic inversion recovery preparation. In both cases, the magnetization preparation was integrated into a 3D UTE acquisition, with 16 radial spokes acquired per preparation. Images were acquired from human cadaveric femoral mid-shafts, from which isolated bone samples were subsequently extracted for non-imaging analysis using T2 spectroscopic measurements. The results showed a strong correlation between imaging-derived concentrations of bound and pore water and those determined from the isolated bone samples.