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Browsing Duke Student Scholarship by Affiliation "Biomedical Engineering"
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Item Open Access Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.(2010) Sinclair, Steven MichaelSTUDY DESIGN: The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro. OBJECTIVE: To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro. SUMMARY OF BACKGROUND DATA: TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown. METHODS: IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells. RESULTS: Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively. CONCLUSION: Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.Item Open Access Comparative performance of multiview stereoscopic and mammographic display modalities for breast lesion detection.(2010) Webb, Lincoln JonPURPOSE: Mammography is known to be one of the most difficult radiographic exams to interpret. Mammography has important limitations, including the superposition of normal tissue that can obscure a mass, chance alignment of normal tissue to mimic a true lesion and the inability to derive volumetric information. It has been shown that stereomammography can overcome these deficiencies by showing that layers of normal tissue lay at different depths. If standard stereomammography (i.e., a single stereoscopic pair consisting of two projection images) can significantly improve lesion detection, how will multiview stereoscopy (MVS), where many projection images are used, compare to mammography? The aim of this study was to assess the relative performance of MVS compared to mammography for breast mass detection. METHODS: The MVS image sets consisted of the 25 raw projection images acquired over an arc of approximately 45 degrees using a Siemens prototype breast tomosynthesis system. The mammograms were acquired using a commercial Siemens FFDM system. The raw data were taken from both of these systems for 27 cases and realistic simulated mass lesions were added to duplicates of the 27 images at the same local contrast. The images with lesions (27 mammography and 27 MVS) and the images without lesions (27 mammography and 27 MVS) were then postprocessed to provide comparable and representative image appearance across the two modalities. All 108 image sets were shown to five full-time breast imaging radiologists in random order on a state-of-the-art stereoscopic display. The observers were asked to give a confidence rating for each image (0 for lesion definitely not present, 100 for lesion definitely present). The ratings were then compiled and processed using ROC and variance analysis. RESULTS: The mean AUC for the five observers was 0.614 +/- 0.055 for mammography and 0.778 +/- 0.052 for multiview stereoscopy. The difference of 0.164 +/- 0.065 was statistically significant with a p-value of 0.0148. CONCLUSIONS: The differences in the AUCs and the p-value suggest that multiview stereoscopy has a statistically significant advantage over mammography in the detection of simulated breast masses. This highlights the dominance of anatomical noise compared to quantum noise for breast mass detection. It also shows that significant lesion detection can be achieved with MVS without any of the artifacts associated with tomosynthesis.Item Open Access Harmonic source wavefront aberration correction for ultrasound imaging.(2010) Dianis, Scott W.Aberration is a correctable phenomenon that degrades diagnostic quality in a significant number of ultrasound images. Previous aberration correction studies have focused on development of aberration estimation algorithms or on aberration reduction by using harmonic imaging. In the past, a major drawback of aberration estimation algorithms has been the assumptions required about the imaging target, assumptions that can limit clinical application where correction for multiple locations within a scan may be required. Harmonic imaging attempts to reduce the effect of aberration, without making assumptions about the imaging target, by using a lower-frequency transmit beam that is less prone to aberration. However, harmonic imaging does not correct for any aberration that may remain. It is hypothesized that a harmonic source wavefront correction technique is capable of creating a point-like acoustical source that allows for estimation and correction of two-dimensional aberration in a clinical setting. Harmonic source wavefront correction utilizes the reduced aberration of harmonic imaging to create a known acoustical source to satisfy the assumptions of the aberration estimation algorithms, thus improving their clinical application. Generation of a point-like acoustical source in the presence of aberration is demonstrated using both spatially correlated and spatially uncorrelated electronic aberrators varying in strength from 0.25π radians to 1.16π radians RMS focusing error. Beam properties of the 2.08 MHz fundamental, 4.16 MHz generated harmonic, and 4.17 MHz imaging beams were compared; in the presence of aberration, relative peak beam amplitude of the 4.16 MHz generated harmonic beam was up to 81% higher than the 4.17 MHz imaging beam, while -6 dB beam width indicated the 4.16 MHz generated harmonic beam was 88% narrower and more point-like than the 2.08 MHz fundamental beam. The feasibility of harmonic source wavefront correction was demonstrated by correcting for spatially uncorrelated electronic aberrators in a water tank using a point target, specular reflector, and speckle region as correction targets. Harmonic source wavefront correction was paired with a cross-correlation algorithm to estimate corrective delays and was most effective in correcting peak amplitude of the 4.17 MHz imaging beam using a point target (up to 94% improvement), followed by use of a specular reflector (up to 83% improvement), followed by use of a speckle region (up to 47% improvement). Aberration correction is sensitive to signal-to-noise ratio (SNR),and correction utilizing the 2.08 MHz fundamental, which provided higher SNR, was more effective than correction utilizing the more point-like 4.16 MHz harmonic for the experimental setup used. A harmonic SNR of 14 dB was estimated as necessary for harmonic-based correction performance to equal or surpass fundamental-based correction, regardless of fundamental SNR. Finally, performance of harmonic source wavefront correction was quantified in a clinical setting. Correction of spatially correlated electronic aberrators was performed using both ex vivo porcine kidneys and the left kidneys of 11 human volunteers as correction targets. Correction utilizing porcine kidney resulted in 10 dB greater improvement in peak beam amplitude than correction utilizing the left kidney of human volunteers. Body wall aberration present in the human volunteers was not accounted for during correction and likely caused the disparity in correction performance. An average upper limit for body wall aberration for the human subjects was estimated at 65 ns (±9 ns) RMSItem Open Access Knowledge-based IMRT treatment planning for prostate cancer.(2011) Chanyavanich, VorakarnThe goal of intensity-modulated radiation therapy (IMRT) treatment plan optimization is to produce a cumulative dose distribution that satisfies both the dose prescription and the normal tissue dose constraints. The typical manual treatment planning process is iterative, time consuming, and highly dependent on the skill and experience of the planner. We have addressed this problem by developing a knowledge based approach that utilizes a database of prior plans to leverage the planning expertise of physicians and physicists at our institution. We developed a case-similarity algorithm that uses mutual information to identify a similar matched case for a given query case, and various treatment parameters from the matched case are then adapted to derive new treatment plans that are patient specific. We used 10 randomly selected cases matched against a knowledge base of 100 cases to demonstrate that new, clinically acceptable IMRT treatment plans can be developed. This approach substantially reduced planning time by skipping all but the last few iterations of the optimization process. Additionally, we established a simple metric based on the areas under the curve (AUC) of the dose volume histogram (DVH), specifically for the planning target volume (PTV), rectum, and bladder. This plan quality metric was used to successfully rank order the plan quality of a collection of knowledgebased plans. Further, we used 100 pre-optimized plans (20 query x 5 matches) to show that the average normalized MI score can be used as a surrogate of overall plan quality. Plans of lower pre-optimized plan quality tended to improve substantially after optimization, though its final plan quality did not improve to the same level as a plan that has a higher pre-optimized plan quality to begin with. Optimization usually improved PTV coverage slightly while providing substantial dose sparing for both bladder and rectum of 12.4% and 9.1% respectively. Lastly, we developed new treatment plans for cases selected from an outside institution matched against our sitespecific database. The knowledge-based plans are very comparable to the original manual plan, providing adequate PTV coverage as well as substantial improvement in dose sparing to the rectum and bladder. In conclusion, we found that a site-specific database of prior plans can be effectively used to design new treatment plans for our own institution as well as outside cases. Specifically, knowledge-based plans can provide clinically acceptable planning target volume coverage and clinically acceptable dose sparing to the rectum and bladder. This approach has been demonstrated to improve the efficiency of the treatment planning process, and may potentially improve the quality of patient care by enabling more consistent treatment planning across institutions.Item Open Access Optimized approach to decision fusion of heterogeneous data for breast cancer diagnosis.(Med Phys, 2006-08) Jesneck, Jonathan LeeAs more diagnostic testing options become available to physicians, it becomes more difficult to combine various types of medical information together in order to optimize the overall diagnosis. To improve diagnostic performance, here we introduce an approach to optimize a decision-fusion technique to combine heterogeneous information, such as from different modalities, feature categories, or institutions. For classifier comparison we used two performance metrics: The receiving operator characteristic (ROC) area under the curve [area under the ROC curve (AUC)] and the normalized partial area under the curve (pAUC). This study used four classifiers: Linear discriminant analysis (LDA), artificial neural network (ANN), and two variants of our decision-fusion technique, AUC-optimized (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these classifiers with 100-fold cross-validation to two heterogeneous breast cancer data sets: One of mass lesion features and a much more challenging one of microcalcification lesion features. For the calcification data set, DF-A outperformed the other classifiers in terms of AUC (p < 0.02) and achieved AUC=0.85 +/- 0.01. The DF-P surpassed the other classifiers in terms of pAUC (p < 0.01) and reached pAUC=0.38 +/- 0.02. For the mass data set, DF-A outperformed both the ANN and the LDA (p < 0.04) and achieved AUC=0.94 +/- 0.01. Although for this data set there were no statistically significant differences among the classifiers' pAUC values (pAUC=0.57 +/- 0.07 to 0.67 +/- 0.05, p > 0.10), the DF-P did significantly improve specificity versus the LDA at both 98% and 100% sensitivity (p < 0.04). In conclusion, decision fusion directly optimized clinically significant performance measures, such as AUC and pAUC, and sometimes outperformed two well-known machine-learning techniques when applied to two different breast cancer data sets.Item Open Access Plate-specific gain map correction for the improvement of detective quantum efficiency in computed radiography.(2010) Schnell, Erich A.The purpose of this work is to improve the NPS, and thus DQE, of CR images by correcting for pixel-to-pixel gain variations specific to each plate. Ten high-exposure open field images were taken with an RQA5 spectrum, with a sixth generation CR plate suspended in air without a cassette. Image values were converted to exposure, the plates registered using fiducial dots on the plate, the ten images averaged, and then high-pass filtered to remove low frequency contributions from field inhomogeneity. A gain-map was then produced by converting all pixel values in the average into fractions with mean of one. The resultant gain-map of the plate was used to normalize subsequent single images to correct for pixel-to-pixel gain fluctuation. The normalized NPS (NNPS) for all images was calculated both with and without the gain-map correction. The NNPS with correction showed improvement over the non-corrected case over the range of frequencies from 0.15 –2.5 mm-1. At high exposure (40 mR), NNPS was 50-90% better with gain-map correction than without. A small further improvement in NNPS was seen from careful registering of the gain-map with subsequent images using small fiducial dots, because of slight misregistration during scanning. CR devices have not traditionally employed gain-map corrections common with DR detectors because of the multiplicity of plates used with each reader. This study demonstrates that a simple gain-map can be used to correct for the fixed-pattern noise and thus improve the DQE of CR imaging. Such a method could easily be implemented by manufacturers because each plate has a unique bar code and the gain-map could be stored for retrieval after plate reading. These experiments indicated that an improvement in NPS (and hence, DQE) is possible, depending on exposure level,over all frequencies with this technique.Item Open Access Stream segregation on a single electrode as a function of pulse rate in cochlear implant listeners.(2010) Duran, Sara IWhile cochlear implants usually provide a high level of speech recognition in quiet, speech recognition in noise and music appreciation remain challenging. In response to these issues, several studies have proposed increasing the number of channels of information through multiple pulse rate strategies. For the selection of pulse rates, studies of multi-rate strategies have considered implementation issues such as harmonics, pitch saturation, and tonotopic order but have not considered the fundamental perceptual question of whether two pulse rates can provide independent channels of information on a single electrode. This study measures stream segregation as an indicator of whether different pulse rates on the same electrode can be perceived independently. This approach differs from that of previous stream segregation studies which focused on stimulation of alternating electrodes, with the motivation of determining a relationship between electrode stream segregation and speech perception in challenging noisy environments. Stream segregation in this study was measured using two stimulus sequences following an A-B-A-B structure where A and B were different pulse rates stimulatingthe same electrode. The timing between A and B was controlled to provide either aregular or irregular gap between the two pulse trains. The threshold at which subjects could distinguish a regular rhythm from an irregular rhythm was used as an estimate of stream segregation since detecting an irregular rhythm is an easier task when the streams are fused. Stream segregation in cochlear implant users, as with normal hearing listeners, was hypothesized to be influenced by factors such as frequency and the relative timing between tones. To attempt to assess the relationship between these and stream segregation, subjects’ rate discrimination and gap detection abilities were also measured. The results of this study indicate that stream segregation can occur for two pulse rates on a single electrode; thus, it may be possible to use pulse rates to create additional channels of information. Further, the stream segregation results were not strongly correlated with the gap detection or rate discrimination results. The lack of correlation with the gap detection results suggests that the task was measuring a separate perceptual phenomenon rather than providing another measure of gap detection. The lack of correlation with the rate discrimination results suggests that discriminability may not be a limiting factor in selecting rates for segregation. These results may have implications for the future design of multi-rate speech processing strategies.Item Open Access The effects of osmotic stress on the structure and function of the cell nucleus.(2010) Finan, John DesmondChondrocytes maintain cartilage by transducing joint load into appropriate biosynthetic activity, a process commonly known as mechanotransduction. Malfunctioning mechanotransduction leads to cartilage degradation and osteoarthritis. The mechanism of mechanotransduction is only partially understood but osmotic stresses are thought to play an important role. This study shows that the chondrocyte nucleus shrinks and wrinkles under hyper-osmotic stress. It shrinks because the chromatin inside the nucleus contracts as the macromolecules in the cell become more crowded. It wrinkles because the nuclear lamina buckles as the nucleus contracts. These morphological changes accelerate transport across the nuclear envelope. Many cells have organized actin caps around their nuclei that constrain the nucleus from contracting under hyper-osmotic stress. Agents exist that can reverse this loss of osmotic sensitivity in vitro without damaging the cell.