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Libération localisée d’ATP cellulaire par ultrasons et microbulles pour l’immunothérapie du cancerDemeze Kenfack, Falonne 03 1900 (has links)
Plusieurs types cancéreux prolifèrent par leur capacité à exprimer les marqueurs de régulation négative du système immunitaire, tels que les récepteurs PD-L1 et CD80/86 qui inhibent l’activation et la prolifération des lymphocytes T. L’inhibition de ces voies par des anticorps peut ainsi réactiver la réponse immunitaire chez certains patients. D’autres voies de signalisations sont aujourd’hui explorées, incluant la signalisation purinergique (ATP/adénosine) dans la modulation du microenvironnement tumoral. L’adénosine triphosphate extracellulaire (ATPe) est classifiée parmi les molécules de danger extracellulaire et joue un rôle crucial dans l’activation de l’inflammasome NLRP3, un médiateur important de l’activation des réactions pro-inflammatoires. Les ultrasons sont des ondes mécaniques de haute pression capable d’engendrer la cavitation inertielle des microbulles. Il a été démontré que les microbulles (MB) stimulées par ultrasons (US) libèrent de l’ATP dans le muscle squelettique et dans le muscle cardiaque. Nous posons l’hypothèse selon laquelle le traitement US+MB appliqué sur une tumeur de cancer du sein murin (4T1) in vivo peut libérer de l’ATPe localement dans le but d’activer des réactions pro-inflammatoires pour l’immunothérapie du cancer. Dans ce mémoire, nous présentons la quantification du signal d’ATPe d’une culture de cellules 4T1, puis in vivo dans le muscle et dans une tumeur solide sous-cutanée chez la souris à la suite d’une stimulation par US+MB. Nos études démontrent que la thérapie US+MB libère de l’ATP in vitro et in vivo. En comparant le signal découlant de l’injection IM d’ATP avec celui du muscle et des tumeurs post-US+MB, nous pouvons conclure que le traitement US+MB libère une quantité d’ATPe supérieure à 250 µM, ce qui est supérieur à la quantité d’ATPe dans un microenvironnement tumoral et qui persiste pour une durée d’au moins 60 min dans le muscle et 45 min dans la tumeur. La transfection stable de cellules MC38 (carcinome colorectal) à travers le gène PLenti-PmeLUC, codant la synthèse de luciférase sur la face externe de la membrane cellulaire, est explorée afin d’augmenter le rapport signal sur bruit en bioluminescence (annexe A). L’utilisation de POM-1 (inhibiteur pharmacologique de CD39) et l’utilisation de souris knockout du gène CD39 sont discutées pour la suite du projet afin d’inhiber la dégradation de l’ATP extracellulaire (Annexe B). / Several cancer types proliferate due to their ability to express the negative regulatory markers of the immune system (PD-L1 and CD80/86) which inhibit the activation and proliferation of T cells. Inhibition of these pathways by antibodies (anti-PDL-1, anti-PD-1, anti-CTLA-4) can thus reactivate the immune system in some patients. Other signaling pathways are currently being explored, including purinergic signaling (ATP/adenosine) in the modulation of the tumor microenvironment. Extracellular Adenosine triphosphate (eATP) is classified as danger signal plays a critical role in the activation of the NLRP3 inflammasome, an important mediator of the innate immune response. Ultrasound (US) and microbubbles (MB) have been shown to release ATP in skeletal and cardiac muscle. Thus, we hypothesized that US+MB treatment in 4T1 breast cancer cells could locally activate pro-inflammatory responses by releasing an eATP in tumors for cancer immunotherapy. In this thesis, I present the quantification of the eATP signal after US+MB stimulation in vitro (4T1 cell culture), then in muscle and subcutaneous solid tumors in the mouse. Our studies demonstrate that US+MB treatment releases ATP both in vitro and in vivo. In comparison with the IM injection of ATP, we can conclude that US+MB released a large amount of ATP (>250 µM), which is more than the eATP concentration in the untreated tumor microenvironment, and which persisted for at least 60 min in muscle and 45 min in tumor. The stable transfection of MC38 cells (colorectal carcinoma) through the Plenti-PmeLUC gene, encoding the synthesis of luciferase on the external surface of cell membrane is explored to increase the signal to noise ratio in bioluminescence (see appendix A). The use of POM-1 (pharmacological inhibitor of CD39) and CD39 gene knockout mice to inhibit the degradation of eATP signal are discussed for the continuation of the project.
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Experimental characterization of stress corrosion cracking sensitization in austenitic stainless steel using nonlinear ultrasonic Rayleigh wavesLakocy, Alexander J. 07 January 2016 (has links)
This thesis examines the use of nonlinear ultrasound to evaluate sensitization, a precursor to stress corrosion cracking in austenitic stainless steel. Ultrasonic Rayleigh surface waves are generated on a specimen; as these waves pass through sensitized material, second harmonic generation (SHG) increases. In austenitic stainless steel with oven-induced sensitization, this increase is due only to the formation of chromium carbide precipitates, key products of the sensitization process. Weld-induced sensitization specimens demonstrate additional increases in SHG, likely caused by increased residual stress and dislocation density as a result of uneven heating. Experimental data are used to calculate the acoustic nonlinearity parameter, which provides a single value directly related to the quantity of micro- and nano-scale damage present within any given sample. Using this procedure, the effects of weld- and oven-induced sensitization are compared. Results demonstrate the feasibility of using nonlinear Rayleigh waves to detect and monitor stress corrosion susceptibility of welded material.
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Association of single nucleotide polymorphisms in the leptin gene and segregation by ultrasound backfat at weaning on carcass performance in steersBreiner, Ryan Michael January 1900 (has links)
Master of Science / Department of Animal Sciences and Industry / Twig T. Marston / One hundred ninety-three crossbred steers from two herds were used to determine the association of leptin gene polymorphisms and effects of feedlot management of lean and fat steers on carcass performance. Steers were sorted into FAT and LEAN groups by ultrasound backfat at weaning and randomly assigned to a finishing phase. Steers were assigned to a backgrounding phase (BACK) and were fed a forage-based diet for 90 days or directly entered a feedlot phase (FEED). Genotypes were determined by IGENITY® (Atlanta, GA) for a panel of nine single nucleotide polymorphisms (SNP) in the leptin gene (UASMS1, UASMS2, C963T, E2FB, A1457G, and A252T), leptin receptor (T945M), growth hormone receptor (G200A), and fat metabolism enzyme (K232A). Initial backfat (BF) means for the FAT and LEAN group were 3.4 mm and 1.8 mm, respectively. Mean on-test weight was heavier for FAT (306.5 kg) than LEAN (292.9 kg). Age-adjusted hot carcass weights (HCWT) were heavier for LEAN/BACK when compared to FAT/FEED and FAT/BACK (P<0.05). Dressing percent for the FAT/FEED group tended to be higher (P<0.10) over all groups except LEAN/BACK. Steers that went directly to the feedlot had higher marbling scores than backgrounded groups. FAT/FEED had higher 12th rib BF than the other contemporaries. None of the SNPs were useful for predicting ultrasound BF at weaning. Some association was detected with UASMS2 and HCWT (P<0.10) resulting in an 11 kg difference between genotype CC and CT (P<0.05). Five of the leptin polymorphisms (UASMS1, UASMS2, A1457G, C963T, and E2FB) were associated with adjusted carcass BF (P=0.01, 0.06, 0.01, 0.01, and 0.01, respectively) and calculated yield grade (P<0.01). A252T was associated with REA, and genotype TT was larger than AA and AT (P<0.05). This study suggests that segregation by initial fatness estimates and feedlot management strategies has the opportunity to increase HCWT by 35 kg. Sorting cattle upon
feedlot entry by ultrasound BF and segregation using genetic markers are useful tools that can assist in the estimation of carcass composition in the live animal. With additional research, the possibility exists to incorporate genetic markers into feedlot selection to assist in marketing decisions.
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Sonography and hypotension: a change to critical problem solving in undergraduate medical educationAmini, Richard, Stolz, Lori A, Hernandez, Nicholas C, Gaskin, Kevin, Baker, Nicola, Sanders, Arthur Barry, Adhikari, Srikar 14 January 2016 (has links)
UA Open Access Publishing Fund / Study objectives: Multiple curricula have been designed to teach medical students the basics
of ultrasound; however, few focus on critical problem-solving. The objective of this study is to
determine whether a theme-based ultrasound teaching session, dedicated to the use of ultrasound
in the management of the hypotensive patient, can impact medical students’ ultrasound education
and provide critical problem-solving exercises.
Methods: This was a cross-sectional study using an innovative approach to train 3rd year
medical students during a 1-day ultrasound training session. The students received a 1-hour
didactic session on basic ultrasound physics and knobology and were also provided with YouTube
hyperlinks, and links to smart phone educational applications, which demonstrated a variety
of bedside ultrasound techniques. In small group sessions, students learned how to evaluate
patients for pathology associated with hypotension. A knowledge assessment questionnaire was
administered at the end of the session and again 3 months later. Student knowledge was also
assessed using different clinical scenarios with multiple-choice questions.
Results: One hundred and three 3rd year medical students participated in this study. Appropriate
type of ultrasound was selected and accurate diagnosis was made in different hypotension clinical
scenarios: pulmonary embolism, 81% (95% CI, 73%–89%); abdominal aortic aneurysm,
100%; and pneumothorax, 89% (95% CI, 82%–95%). The average confidence level in performing
ultrasound-guided central line placement was 7/10, focused assessment with sonography
for trauma was 8/10, inferior vena cava assessment was 8/10, evaluation for abdominal aortic
aneurysm was 8/10, assessment for deep vein thrombus was 8/10, and cardiac ultrasound for
contractility and overall function was 7/10. Student performance in the knowledge assessment
portion of the questionnaire was an average of 74% (SD =11%) at the end of workshop and
74% (SD =12%) 3 months later (P=0.00).
Conclusion: At our institution, we successfully integrated ultrasound and critical problemsolving
instruction, as part of a 1-day workshop for undergraduate medical education
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Bubbles : sensors for the micro worldHarfield, Caroline Jane January 2014 (has links)
It has been proposed that coated gas microbubbles, currently used as ultrasound contrast agents could also be used as microscale sensors due to the sensitivity of their acoustic response to changes in their environment. However, their behaviour is not fully understood and there remains considerable scope for improving their characterisation. The aim of this thesis is to improve the theoretical description of microbubble dynamics under ultrasound excitation with the ultimate aim of assessing the regimes in which they could be exploited most effectively as sensors. Previous theoretical and experimental work relating to the confinement and acoustic excitation of microbubbles is reviewed. Specifically, optical trapping as a method for the isolation and manipulation of individual bubbles is studied for use in developing a sensor. An assessment of the existing models’ validity is undertaken. This is followed by the development of models for optical trapping of single microbubbles, and the coupled radial and translational motion of a microbubble under ultrasound excitation, which includes time dependent phenomena. The latter model is used to perform a sensitivity analysis to determine the uncertainty associated with using microbubbles as sensors. The potential for uniquely characterising the shell of the microbubble from experimental data is also assessed. Subsequent chapters present the results from a combination of computer simulations and experimental data, used to develop and assess the validity of the new models for describing microbubble behaviour. Particularly, the model is used to simulate the response of a dilute suspension of microbubbles undergoing large amplitude oscillations and single microbubbles undergoing lipid shedding. The optimal regimes in which microbubbles may be utilised as sensors for liquid physical properties and local pressure variations are then assessed. Finally, a summary of the conclusions and areas for further work is presented.
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On the assessment of blood velocity and wall shear rate in arteries with Doppler ultrasound : a validation studyBlake, James R. January 2008 (has links)
Cardiovascular disease, mostly atherosclerosis, is responsible for one third of all deaths globally, rising to more than 50% in the Western World. Risk factors include smoking, diet, and familial history. Doppler ultrasound can provide estimates of blood velocity and wall shear rate. Clinically, maximum velocity is used to categorise patients for surgery, although Doppler velocity measurement is prone to errors and in need of validation. Wall shear stress—which can be derived from wall shear rate—plays a role in disease initiation and progression, although its clinical utility is unclear due to difficulties associated with its measurement. This thesis investigates the use of Doppler ultrasound as a tool to estimate blood velocity and wall shear rate. A simplified method for estimation of wall shear rate in healthy arteries is developed that uses spectral Doppler ultrasound. This method is based upon the theory of oscillatory flow in rigid pipes, requiring two measurements that are readily available with clinical ultrasound machines. This method is compared to a similar method based on colour flow imaging. The spectral Doppler method underestimated the theoretic value of wall shear rate by between 7 and 22%, with results varying between phantoms. Errors for the colour method were on average 35% greater. Test measurements from one healthy volunteer demonstrated that this method can be applied in-vivo. In more advanced stages of disease, peak velocity distal to a stenosis is of clinical interest and the simplified method for wall shear rate estimation is invalid. Steady flow in a series of simplified stenosis geometries was studied using a dual-beam Doppler system to obtain velocity vectors. These measurements were compared with data from an equivalent system that used particle image velocimetry (PIV) and was considered the gold standard. For Reynolds numbers at the stenosis throat of less than 800, flow remained laminar over the region studied, although distal flow separation did occur. For higher throat Reynolds numbers—corresponding to more severe stenoses or increased flow rates—asymmetric recirculation regions developed; the transition to turbulence occurred more proximally, with a corresponding reduction in stenotic jet and recirculation length. Qualitative agreement was observed in the velocity profile shapes measured using ultrasound and PIV at throat Reynolds numbers less than 800. Above this threshold the qualitative agreement between the velocity profiles became poorer as both downstream distance and the degree of stenosis increased. Peak axial velocity distal to the stenosis was underestimated, on average, by 15% in the ultrasound system. Estimation of shear rate remained difficult with both experimental techniques. Under a Newtonian approximation, the normalised wall shear stresses agree qualitatively. Under pulsatile flow conditions using an idealised flow waveform, superior qualitative agreement was observed in the velocity profiles at diastole than at systole. Similar to the steady flow behaviour, this agreement deteriorated with stenosis severity. The current generation of clinical ultrasound machines are capable of estimating the wall shear rate in healthy arteries. In the presence of significant arterial disease, errors in the peak velocity may result in mis-selection of patients for surgery, while estimation of the wall shear stress remains extremely problematic; particularly with identifying the wall location and measuring velocities close to the wall.
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Phase-Change Contrast Agents for Targeting and DeliveryHadinger, Kyle January 2016 (has links)
Phase-change contrast agents (PCCAs) are an innovative form of imaging agent with practical applications in both the research and clinical settings. PCCAs are derived from gaseous microbubbles, which are able to act as targeted-contrast agents through conjugation of a ligand that is selective for an overexpressed receptor or biomarker in a given disease. Gaseous microbubbles can be condensed to liquid phase nanodroplets, which should be sufficiently small to extravasate into cells and/or tissues given their size and stability. Once liquid nanodroplets have internalized within a given tissue, they can be "activated" back into gaseous microbubbles with ultrasound at clinically used frequencies and energy outputs. This is purposeful as microbubbles provide much greater ultrasound reflectivity than nanodroplets. In this study, PCCAs and/or microbubbles act as a targeting agent in multiple scenarios. The projects in this study include- examination of binding and internalization of targeted PCCAs with different gaseous cores within MDA-MB-231 breast cancer cells, vaporization of liquid phase nanodroplets through application of acoustic energy via focused ultrasound (FUS), and targeting vulnerable plaque in the heart with different types of targeted microbubbles under varying shear-stresses.
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Use of Ultrasonic Imaging to Evaluate Egg Maturation of Humpback Chub Gila CyphaBrizendine, Morgan E. January 2016 (has links)
Humpback Chub Gila cypha are endangered cyprinids endemic to the Colorado River drainage and are adapted to live in fast currents of warm, turbid water. Although nine known aggregations of Humpback Chub currently exist in the main-stem Colorado River in the Grand Canyon, little is known about their reproduction. I hypothesized that Colorado River water temperatures below Glen Canyon Dam are too low due to hypolimnetic water releases from Lake Powell for female Humpback Chub to develop mature eggs for spawning. Ultrasonic imaging, also called ultrasound, is an effective, non-lethal method used to determine sex and maturity of a variety of freshwater, anadromous, and marine fishes. However, many previous studies have been performed in laboratory environments. I developed a standardized method for ultrasonically scanning endangered Humpback Chub Gila cypha in remote locations within Grand Canyon, Arizona, USA. This method minimized stress to individual fish and took less than 1 min to perform. I was able to identify female fish with eggs based on two jpeg images and one 10 s video clip collected in the field. I also used ImageJ®, a National Institute of Health image processing program, to develop a brightness index to evaluate the maturity of eggs in female fish. I collected ultrasonic scans of captive, ripe Humpback Chub held at the Southwestern Native Aquatic Resources and Recovery Center (SNARRC) to determine that female fish were potentially ripe when a subsample of their eggs exhibited a brightness value within the 32-44 range. Although I was able to estimate egg maturity, I was not able to estimate egg mass of female fish. I used ultrasound to evaluate reproductive condition of 751 Humpback Chub in Grand Canyon. I documented egg development in female fish from the main-stem Colorado River, Little Colorado River, Havasu Creek, and Shinumo Creek. Egg development in Humpback Chub varies by location and time of year. Potentially ripe (stage 3) female fish were found at all sample locations and dates except at Shinumo Creek in 2013 and 2014. Potentially ripe females were also detected in every main-stem aggregation except for Pumpkin Springs and in two locations outside of established aggregations. Fisheries managers can use ultrasound to collect vital information about the reproductive status of fishes that cannot be killed and that are found in remote or rugged field locations. My findings indicate that female Humpback Chub are able to produce eggs throughout the main-stem Colorado River and that internal egg development and egg production likely do not limit recruitment. However, female fish may never experience the environmental triggers they need to spawn or may not experience conditions that would allow eggs and larvae to survive.
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Ultrasound-assisted transthoracic diagnostic techniquesKoegelenberg, Coenraad Frederik Nicolaas 12 1900 (has links)
Thesis (PhD)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Although transthoracic ultrasonography is a well established modality, it is still
underutilised by chest physicians. The aim of this research project was to
investigate the feasibility, diagnostic yield and safety of ultrasound(US)-assisted
transthoracic biopsies performed by clinicians in various settings relevant to daily
practice of respiratory medicine. We conducted four clinical trials which are
summarised below: 1. In a prospective study on the feasibility of US-assisted transthoracic fine
needle aspiration (TTFNA) of drowned lung secondary to a proximal mass
lesion, a novel indication for US-assisted TTFNA was described. TTFNA
passes >20mm from the visceral pleura had a sensitivity of 74.2% and
were also more likely to contain malignant cells than more superficial
passes. The surprisingly high yield and the fact that no serious
complications were observed validated this approach, which may be an
alternative to bronchoscopy.
2. In the largest single-centre study on US-assisted TTFNA with rapid on-site
evaluation (ROSE) and cutting needle biopsy (CNB) in the setting of
superior vena cava (SVC) syndrome ever reported, we were able to
accurately diagnose 96% of all patients who presented with an associated
mass lesion that abutted or infiltrated the chest wall. No pneumothoraces
or major haemorrhage was caused. We also validated the single-session approach, and were able to conclude that US-assisted TTFNA (with
ROSE) is the initial investigation of choice in suspected bronchogenic
carcinoma, whereas both TTFNA and CNB need to be performed in all
other cases. 3. We continued to validate the novel single-session sequential approach in
a study on anterosuperior mediastinal masses. US-assisted TTFNA with
ROSE was performed on 45 consecutive patients, immediately followed
by CNB where a provisional diagnosis of epithelial carcinoma or probable
tuberculosis (TB) could not be established. An accurate cytological
diagnosis was made in 73.3%, and was more likely to be diagnostic in
epithelial carcinoma and TB than all other pathology (p<0.001). CNB
yielded a diagnosis in 88.2%. Overall 93.3% of patients were diagnosed
by the single-session approach. No pneumothorax or major haemorrhage
was observed. 4. In a prospective study, we compared US-assisted Abrams and Tru-Cut
needle biopsies with regard to their yield for pleural TB. Pleural biopsy
specimens obtained with Abrams needles contained pleural tissue in
91.0% of cases and were diagnostic in 81.8%, whereas Tru-Cut needle
biopsy specimens only contained pleural tissue in 78.7% (p=0.015) and
were diagnostic in 65.2% (p=0.022). In conclusion, we investigated the feasibility of US-assisted biopsies performed
by respiratory physicians in various settings, and consistently found acceptable
to very high diagnostic yields with minimal complications. Furthermore, we were
able to validate a novel indication for US-assisted TTFNA (US-assisted TTFNA of
drowned lung), validate the use of a single-session sequential approach (USassisted
TTFNA with ROSE followed by CNB where indicated) in at least two
clinical settings (SVC syndrome and anterosuperior mediastinal masses) and we
were able to show that US-assisted Abrams needle biopsy is superior to Tru-Cut
needles biopsy when histological confirmation of TB pleuritis is required. / AFRIKAANSE OPSOMMING: Alhoewel transtorakale ultrasonografie ‘n gevestigde modaliteit is, word dit
onderbenut deur pulmonoloë. Die doel van hierdie navorsingsprojek was om die
praktiese uitvoerbaarheid, diagnostiese opbrengs en veiligheid van sonargerigte
transtorakale biopsies uitgevoer deur klinici in verskeie situasies relevant tot die
alledaagse praktyk te ontleed. Ons het vier kliniese proewe uitgevoer wat
hieronder opgesom word:
1. In ‘n prospektiewe studie oor die praktiese uitvoerbaarheid van
sonargerigte transtorakale fyn naald aspirasie (TTFNA) van areas van
obstruktiewe pneumonitis sekondêr tot proksimale massa letsels, is ‘n
nuwe indikasie vir sonargerigte TTFNA beskryf. TTFNA aspirasies wat >20mm van die visserale pleura geneem is, het ‘n sensitiwiteit van 74.2%
gehad en was meer geneig om maligne selle op te lewer as meer
oppervlakkige aspirasies. Die verbasende hoë diagnostiese sensitiwiteit
en afwesigheid van ernstige komplikasies het die praktiese waarde van
hierdie benadering bevestig.
2. In die grootste studie nog oor sonargerigte TTFNA met spoedige in-teater
evalusies (SITE) en sny-naald biopsie (SNB) in die teenwoordigheid van
superior vena cava (SVC) sindroom, kon ons 96% van pasiënte wat
presenteer het met ‘n geassosieerde massa letsel wat die borskaswand betrek, akkuraat diagnoseer. Geen pneumotoraks of major bloeding is
waargeneem nie. Ons kon ook die praktiese uitvoerbaarheid van ‘n enkelsessie
benadering bevestig en kon tot die gevolgtrekking kom dat
sonargerigte TTFNA (met SITE) die aanvanklike ondersoek van keuse is
waar bronguskarsinoom vermoed word, maar dat beide TTFNA en SNB
noodsaaklik is in ander gevalle.
3. Ons het voortgegaan om die waarde van die nuwe enkel-sessie
benadering te bevestig in ‘n studie oor antero-superior mediastinale
massas. Sonargerigte TTFNA met SITE is uitgevoer op 45 pasiënte en in
gevalle waar ‘n voorlopige diagnose van epiteliale karsinoom of
waarskynlike tuberkulose (TB) nie bevestig kon word nie, is dit onmiddelik
gevolg deur SNB. ‘n Akkurate sitologiese diagnose is gemaak in 73.3%
van gevalle en meer algemeen in epiteliale karsinoom en TB as ander
patologie (p<001). SNB was diagnosties in 88.2%. In 93.3% kon ‘n
diagnose verkry word met die enkel-sessie benadering. Geen
pneumotoraks of major bloeding is waargeneem nie.
4. In ‘n prospektiewe studie is sonargerigte Abrams naald en Tru-Cut naald
biopsies se opbrengs vir pleurale TB met mekaar vergelyk. Pleurale
biopsie monsters wat met ‘n Abrams naalde geneem is, het pleurale
weefsel in 91.0% gevalle getoon en was diagnosties in 81.8%, vergeleke met Tru-Cut naalde wat slegs in 87.7% pleurale weefsel opgelewer het
(p=0.015) en wat net in in 65.2% diagnosties was (p=0.022).
Opsommend het ons die praktiese uitvoerbaarheid van sonargerigte biopsies
uitgevoer deur pulmonoloë in veskeie kliniese situasies nagevors, en het
deurlopend aanvaarbare tot hoë diagnostiese opbrengste gevind met minimale
komplikasies. Verder kon ons ‘n nuwe indikasie vir sonargerigte TTFNA beskryf
en evalueer (sonargerigte TTFNA van obstruktiewe pneumonitis); ‘n enkel-sessie
sekwensiële benadering se waarde bevestig (sonargerigte TTFNA met SITE,
gevolg deur SNB waar aangedui) in ten minste twee kliniese situasies (SVC
sindroom en anterosuperior mediastinale massas); en was dit moontlik om te
bewys dat UK-geleide Abrams naald biopsies superior tot Tru-cut naald biopsies
is in die histologiese bevestiging van TB pleuritis.
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Quality assessments of solder bump interconnections in ball grid array packages using laser ultrasonics and laser interferometerGong, Jie 27 May 2016 (has links)
Surface mount devices (SMDs), such as flip chip packages and ball grid array (BGA) packages are gaining in popularity in microelectronics industry because they provide high density inputs/outputs, better electrical and thermal performance. However, these solder bump interconnections in SMDs are sandwiched between the silicon die and the substrate, which makes them challenging to be inspected. Current non-destructive solder bump inspection techniques like electrical testing, X-ray and acoustic microscopy have some application gaps. New solder bump inspection technique is urgently needed to fill these gaps. Previous work has shown the potential of using a non-contact, non-destructive laser ultrasonics and laser interferometer based inspection system for assessing solder bump qualities. The system uses a pulsed Nd:YAG laser to induce ultrasound in the chip packages and a laser interferometer to measure the transient out-of-plane displacement on the package surface. The quality of the solder bumps can be evaluated by analyzing the out-of-plane displacement. However, there are still some gaps that need to be addressed before the system is ready on the shelf. This dissertation focuses on addressing some of these existing issues. The research work consists of the following: 1) a control interface was developed to integrate all the different modules to achieve automation. 2) a new signal-processing method for analyzing the transient out-of-plane displacement signals without requiring a known-good reference chip was developed. 3) the application scope of the system was expanded to inspect the second level solder bumps in BGA packages. Two types of process-induced defects including poor-wetting and solder bump voids were investigated. Meanwhile, solder bump fatigue caused by cyclic mechanical bending and thermal cycle was also studied using this system. 4) a finite element analysis was performed to study the thermo-mechanical reliability of solder bumps in PBGA package under cyclic thermal loads. The successful completion of the research objectives has led to a laser ultrasound solder bump inspection system prototype with more user-friendliness, higher throughputs, better repeatability and more flexibility, which accelerate the commercialization the system.
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