32 resultados para Direct timeintegration methods


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BACKGROUND AND PURPOSE: The major goal of acute ischemic stroke treatment is fast and sufficient recanalization. Percutaneous transluminal balloon angioplasty (PTA) and/or placement of a stent might achieve both by compressing the thrombus at the occlusion site. This study assesses the feasibility, recanalization rate, and complications of the 2 techniques in an animal model. MATERIALS AND METHODS: Thirty cranial vessels of 7 swine were occluded by injection of radiopaque thrombi. Fifteen vessel occlusions were treated by PTA alone and 15, by placement of a stent and postdilation. Recanalization was documented immediately after treatment and after 1, 2, and 3 hours. Thromboembolic events and dissections were documented. RESULTS: PTA was significantly faster to perform (mean, 16.6 minutes versus 33.0 minutes for stent placement; P < .001), but the mean recanalization rate after 1 hour was significantly better after stent placement compared with PTA alone (67.5% versus 14.6%, P < .001). Due to the self-expanding force of the stent, vessel diameter further increased with time, whereas the recanalization result after PTA was prone to reocclusion. Besides thromboembolic events related to the passing maneuvers at the occlusion site, no thrombus fragmentation and embolization occurred during balloon inflation or stent deployment. Flow to side branches could also be restored at the occlusion site because it was possible to direct thrombus compression. CONCLUSIONS: Stent placement and postdilation proved to be much more efficient in terms of acute and short-term vessel recanalization compared with PTA alone.

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The tremendous application potential of nanosized materials stays in sharp contrast to a growing number of critical reports of their potential toxicity. Applications of in vitro methods to assess nanoparticles are severely limited through difficulties in exposing cells of the respiratory tract directly to airborne engineered nanoparticles. We present a completely new approach to expose lung cells to particles generated in situ by flame spray synthesis. Cerium oxide nanoparticles from a single run were produced and simultaneously exposed to the surface of cultured lung cells inside a glovebox. Separately collected samples were used to measure hydrodynamic particle size distribution, shape, and agglomerate morphology. Cell viability was not impaired by the conditions of the glovebox exposure. The tightness of the lung cell monolayer, the mean total lamellar body volume, and the generation of oxidative DNA damage revealed a dose-dependent cellular response to the airborne engineered nanoparticles. The direct combination of production and exposure allows studying particle toxicity in a simple and reproducible way under environmental conditions.

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INTRODUCTION: Using a rat model, we evaluated the kinetics and histomorphometry of ectopic bone formation in association with biomimetic implant coatings containing BMP-2. MATERIALS AND METHODS: One experimental and three control groups were set up: titanium-alloy discs coated with a biomimetically co-precipitated layer of calcium phosphate and BMP-2 [1.7 microg per disc (incorporated-BMP group)]; uncoated discs (control); discs biomimetically coated with a layer of calcium phosphate alone (control); and discs biomimetically coated with a layer of calcium phosphate bearing superficially adsorbed BMP-2 [0.98 microg per disc (control)]. Discs (n = 6 per group) were implanted subcutaneously in rats and retrieved at 7-day intervals over a period of 5 weeks for kinetic, histomorphometrical, morphological and histochemical analyses. RESULTS: In the incorporated-BMP-2 group, osteogenic activity was first observed 2 weeks after implantation and thereafter continued unabated until the end of the monitoring period. The net weekly rates of bone formation per disc were 5.8 mm3 at 2 weeks and 3.64 mm3 at 5 weeks. The total volumes of bone formed per disc at these junctures were 5.8 mm3 and 10.3 mm3, respectively. Bone tissue, which was formed by a direct ossification mechanism, was deposited at distances of up to 340 microm from the implant surfaces. The biomimetic coatings were degraded gradually, initially by foreign body giant cells alone and then also by osteoclasts. Forty percent of the coating material (and thus presumably of the incorporated BMP-2) remained at the end of the monitoring period. Hence, 60% of the incorporated BMP-2 had been released. At this 5-week juncture, no bone tissue was associated with any of the control implants. CONCLUSION: BMP-2 incorporated into biomimetic calcium phosphate coatings is capable not only of inducing bone formation at an ectopic site in vivo but also of doing so with a very high potency at a low pharmacological level, and of sustaining this activity for a considerable period of time. The sustainment of osteogenic activity is of great clinical importance for the osseointegration of dental and orthopedic implants.

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Integrating evidence from different imaging modalities is important to overcome specific limitations of any given imaging method, such as insensitivity of the EEG to unsynchronized neural events, or the lack of fMRI sensitivity to events of low metabolic demand. Processes that are visible in one modality may be related in a nontrivial way to other processes visible in another modality and insight may only be obtained by integrating both methods through a common analysis. For example, brain activity at rest seems to be at least partly determined by an interaction of cortical rhythms (visible to EEG but not to fMRI) with sub-cortical activity (visible to fMRI, but usually not to EEG without averaging). A combination of EEG and fMRI data during rest may thus be more informative than the sum of two separate analyses in both modalities. Integration is also an important source of converging evidence about specific aspects and general principles of neural functions and their dysfunctions in certain pathologies. This is because not only electrical, but also energetic, biochemical, hemodynamic and metabolic processes characterize neural states and functions, and because brain structure provides crucial constraints upon neural functions. Focusing on multimodal integration of functional data should not distract from the privileged status of the electric field as the primary direct, noninvasive real-time measure of neural transmission. The preceding chapters illustrate how electrical neuroimaging has turned scalp EEG into an imaging modality which directly captures the full temporal dynamics of neural activity in the brain.

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F. psychrophilum is the causative agent of Bacterial Cold Water Disease (BCW) and Rainbow Trout Fry Syndrome (RTFS). To date, diagnosis relies mainly on direct microscopy or cultural methods. Direct microscopy is fast but not very reliable, whereas cultural methods are reliable but time-consuming and labor-intensive. So far fluorescent in situ hybridization (FISH) has not been used in the diagnosis of flavobacteriosis but it has the potential to rapidly and specifically detect F. psychrophilum in infected tissues. Outbreaks in fish farms, caused by pathogenic strains of Flavobacterium species, are increasingly frequent and there is a need for reliable and cost-effective techniques to rapidly diagnose flavobacterioses. This study is aimed at developing a FISH that could be used for the diagnosis of F. psychrophilum infections in fish. We constructed a generic probe for the genus Flavobacterium ("Pan-Flavo") and two specific probes targeting F. psychrophilum based on 16S rRNA gene sequences. We tested their specificity and sensitivity on pure cultures of different Flavobacterium and other aquatic bacterial species. After assessing their sensitivity and specificity, we established their limit of detection and tested the probes on infected fresh tissues (spleen and skin) and on paraffin-embedded tissues. The results showed high sensitivity and specificity of the probes (100% and 91% for the Pan-Flavo probe and 100% and 97% for the F. psychrophilum probe, respectively). FISH was able to detect F. psychrophilum in infected fish tissues, thus the findings from this study indicate this technique is suitable as a fast and reliable method for the detection of Flavobacterium spp. and F. psychrophilum.

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OBJECTIVES We sought to evaluate the strategy success and short term clinical outcomes of direct stenting via 5 French (F) diagnostic catheters using a novel bare metal stent with integrated delivery system (IDS) (Svelte Medical Systems, New Providence, NJ) and compare the results to a conventionally treated matched group. METHODS Fifteen consecutive patients with lesions deemed suitable for direct stenting using a bare metal stent were included. The primary endpoint was the strategy success defined as the ability to successfully treat a target lesion via a 5 F diagnostic catheter with a good angiographic result (TIMI III flow, residual stenosis ≤20%). Procedure and fluoroscopy times, contrast agent use, cost, and short-term clinical outcomes were compared to a matched group treated via conventional stenting. RESULTS The primary endpoint was reached in 14/15 patients (93%). There were no significant differences in procedural (58.6 min ± 12.7 vs. 57.4 min ± 14.2) or fluoroscopy times (10.0 min ± 4.3 vs.10.1 min ± 3.9) or contrast agent use (193.7 ml ± 54.8 vs. 181.4 ml ± 35.6). However, there were significant reductions in materials used in the study group compared to the control group equating to cost savings of almost US $600 per case (US $212.44 ± 258.09 vs. US $804.69 ± 468.11; P = 0.001). CONCLUSIONS Direct stenting using a novel bare metal stent with an IDS via 5 F diagnostic catheters is a viable alternative to conventional stenting in selected patients and is associated with significant cost savings.

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BACKGROUND Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). METHODS We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. RESULTS The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. CONCLUSIONS This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

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HYPOTHESIS A previously developed image-guided robot system can safely drill a tunnel from the lateral mastoid surface, through the facial recess, to the middle ear, as a viable alternative to conventional mastoidectomy for cochlear electrode insertion. BACKGROUND Direct cochlear access (DCA) provides a minimally invasive tunnel from the lateral surface of the mastoid through the facial recess to the middle ear for cochlear electrode insertion. A safe and effective tunnel drilled through the narrow facial recess requires a highly accurate image-guided surgical system. Previous attempts have relied on patient-specific templates and robotic systems to guide drilling tools. In this study, we report on improvements made to an image-guided surgical robot system developed specifically for this purpose and the resulting accuracy achieved in vitro. MATERIALS AND METHODS The proposed image-guided robotic DCA procedure was carried out bilaterally on 4 whole head cadaver specimens. Specimens were implanted with titanium fiducial markers and imaged with cone-beam CT. A preoperative plan was created using a custom software package wherein relevant anatomical structures of the facial recess were segmented, and a drill trajectory targeting the round window was defined. Patient-to-image registration was performed with the custom robot system to reference the preoperative plan, and the DCA tunnel was drilled in 3 stages with progressively longer drill bits. The position of the drilled tunnel was defined as a line fitted to a point cloud of the segmented tunnel using principle component analysis (PCA function in MatLab). The accuracy of the DCA was then assessed by coregistering preoperative and postoperative image data and measuring the deviation of the drilled tunnel from the plan. The final step of electrode insertion was also performed through the DCA tunnel after manual removal of the promontory through the external auditory canal. RESULTS Drilling error was defined as the lateral deviation of the tool in the plane perpendicular to the drill axis (excluding depth error). Errors of 0.08 ± 0.05 mm and 0.15 ± 0.08 mm were measured on the lateral mastoid surface and at the target on the round window, respectively (n =8). Full electrode insertion was possible for 7 cases. In 1 case, the electrode was partially inserted with 1 contact pair external to the cochlea. CONCLUSION The purpose-built robot system was able to perform a safe and reliable DCA for cochlear implantation. The workflow implemented in this study mimics the envisioned clinical procedure showing the feasibility of future clinical implementation.

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HYPOTHESIS Facial nerve monitoring can be used synchronous with a high-precision robotic tool as a functional warning to prevent of a collision of the drill bit with the facial nerve during direct cochlear access (DCA). BACKGROUND Minimally invasive direct cochlear access (DCA) aims to eliminate the need for a mastoidectomy by drilling a small tunnel through the facial recess to the cochlea with the aid of stereotactic tool guidance. Because the procedure is performed in a blind manner, structures such as the facial nerve are at risk. Neuromonitoring is a commonly used tool to help surgeons identify the facial nerve (FN) during routine surgical procedures in the mastoid. Recently, neuromonitoring technology was integrated into a commercially available drill system enabling real-time monitoring of the FN. The objective of this study was to determine if this drilling system could be used to warn of an impending collision with the FN during robot-assisted DCA. MATERIALS AND METHODS The sheep was chosen as a suitable model for this study because of its similarity to the human ear anatomy. The same surgical workflow applicable to human patients was performed in the animal model. Bone screws, serving as reference fiducials, were placed in the skull near the ear canal. The sheep head was imaged using a computed tomographic scanner and segmentation of FN, mastoid, and other relevant structures as well as planning of drilling trajectories was carried out using a dedicated software tool. During the actual procedure, a surgical drill system was connected to a nerve monitor and guided by a custom built robot system. As the planned trajectories were drilled, stimulation and EMG response signals were recorded. A postoperative analysis was achieved after each surgery to determine the actual drilled positions. RESULTS Using the calibrated pose synchronized with the EMG signals, the precise relationship between distance to FN and EMG with 3 different stimulation intensities could be determined for 11 different tunnels drilled in 3 different subjects. CONCLUSION From the results, it was determined that the current implementation of the neuromonitoring system lacks sensitivity and repeatability necessary to be used as a warning device in robotic DCA. We hypothesize that this is primarily because of the stimulation pattern achieved using a noninsulated drill as a stimulating probe. Further work is necessary to determine whether specific changes to the design can improve the sensitivity and specificity.

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Background: Sevoflurane exerts effects on pulmonary cells that could protect against lung injury. We evaluated the potential of pretreatment with sevoflurane to attenuate lipopolysaccharide (LPS)-induced lung injury. Methods: LPS was administered intratracheally in Wistar rats to induce lung injury. Sevoflurane was administered for 30 min at 0.25, 0.5 or 1.0 MAC 15 min before LPS or for 30min at 0.5 MAC 24 hours before LPS. After initial analysis of bronchoalveolar lavage fluid (BALF) cells and total protein, the group of 0.5 MAC 15min before LPS was further analyzed for surfactant aggregates subfractions, plasma malondialdehyde levels and lung histology. Results: LPS instillation resulted in neutrophils sequestration in the lungs, loss of alveolar macrophages, increased BALF total protein and decreased large surfactant aggregates. Only inhalation of sevoflurane for 30min at 0.5 MAC 15min before LPS installation effectively reduced neutrophil accumulation, preserved alveolar epithelial cells and reduced total protein content in BALF. This regimen also reduced plasma malondialdehyde levels and increased large surfactant aggregates, despite the application of mechanical ventilation. This effect was preserved after LPS instillation and the favorable composition of surfactant was maintained. Conclusions: Pretreatment with sevoflurane effectively attenuates direct severe lung injury, possibly by inhibition of neutrophil accumulation and alteration of the surfactant composition.

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BACKGROUND In Parkinson's disease (PD), bradykinesia, or slowness of movement, only appears after a large striatal dopamine depletion. Compensatory mechanisms probably play a role in this delayed appearance of symptoms. OBJECTIVE Our hypothesis is that the striatal direct and indirect pathways participate in these compensatory mechanisms. METHODS We used the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD and control animals. Four weeks after the lesion, the spontaneous locomotor activity of the rats was measured and then the animals were killed and their brain extracted. We quantified the mRNA expression of markers of the striatal direct and indirect pathways as well as the nigral expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH) mRNA. We also carried out an immunohistochemistry for the striatal TH protein expression. RESULTS As expected, the unilateral 6-OHDA rats presented a tendency to an ipsilateral head turning and a low locomotor velocity. In 6-OHDA rats only, we observed a significant and positive correlation between locomotor velocity and both D1-class dopamine receptor (D1R) (direct pathway) and enkephalin (ENK) (indirect pathway) mRNA in the lesioned striatum, as well as between D1R and ENK mRNA. CONCLUSIONS Our results demonstrate a strong relationship between both direct and indirect pathways and spontaneous locomotor activity in the parkinsonian rat model. We suggest a synergy between both pathways which could play a role in compensatory mechanisms and may contribute to the delayed appearance of bradykinesia in PD.

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Liquid crystals (LCs) represent a challenging group of materials for direct transmission electron microscopy (TEM) studies due to the complications in specimen preparation and the severe radiation damage. In this paper, we summarize a series of specimen preparation methods, including thin film and cryo-sectioning approaches, as a comprehensive toolset enabling high-resolution direct cryo-TEM observation of a broad range of LCs. We also present comparative analysis using cryo-TEM and replica freeze-fracture TEM on both thermotropic and lyotropic LCs. In addition to the revisits of previous practices, some new concepts are introduced, e.g., suspended thermotropic LC thin films, combined high-pressure freezing and cryo-sectioning of lyotropic LCs, and the complementary applications of direct TEM and indirect replica TEM techniques. The significance of subnanometer resolution cryo-TEM observation is demonstrated in a few important issues in LC studies, including providing direct evidences for the existence of nanoscale smectic domains in nematic bent-core thermotropic LCs, comprehensive understanding of the twist-bend nematic phase, and probing the packing of columnar aggregates in lyotropic chromonic LCs. Direct TEM observation opens ways to a variety of TEM techniques, suggesting that TEM (replica, cryo, and in situ techniques), in general, may be a promising part of the solution to the lack of effective structural probe at the molecular scale in LC studies. Microsc. Res. Tech. 77:754-772, 2014. © 2014 Wiley Periodicals, Inc.

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PURPOSE A beamlet based direct aperture optimization (DAO) for modulated electron radiotherapy (MERT) using photon multileaf collimator (pMLC) shaped electron fields is developed and investigated. METHODS The Swiss Monte Carlo Plan (SMCP) allows the calculation of dose distributions for pMLC shaped electron beams. SMCP is interfaced with the Eclipse TPS (Varian Medical Systems, Palo Alto, CA) which can thus be included into the inverse treatment planning process for MERT. This process starts with the import of a CT-scan into Eclipse, the contouring of the target and the organs at risk (OARs), and the choice of the initial electron beam directions. For each electron beam, the number of apertures, their energy, and initial shape are defined. Furthermore, the DAO requires dose-volume constraints for the structures contoured. In order to carry out the DAO efficiently, the initial electron beams are divided into a grid of beamlets. For each of those, the dose distribution is precalculated using a modified electron beam model, resulting in a dose list for each beamlet and energy. Then the DAO is carried out, leading to a set of optimal apertures and corresponding weights. These optimal apertures are now converted into pMLC shaped segments and the dose calculation for each segment is performed. For these dose distributions, a weight optimization process is launched in order to minimize the differences between the dose distribution using the optimal apertures and the pMLC segments. Finally, a deliverable dose distribution for the MERT plan is obtained and loaded back into Eclipse for evaluation. For an idealized water phantom geometry, a MERT treatment plan is created and compared to the plan obtained using a previously developed forward planning strategy. Further, MERT treatment plans for three clinical situations (breast, chest wall, and parotid metastasis of a squamous cell skin carcinoma) are created using the developed inverse planning strategy. The MERT plans are compared to clinical standard treatment plans using photon beams and the differences between the optimal and the deliverable dose distributions are determined. RESULTS For the idealized water phantom geometry, the inversely optimized MERT plan is able to obtain the same PTV coverage, but with an improved OAR sparing compared to the forwardly optimized plan. Regarding the right-sided breast case, the MERT plan is able to reduce the lung volume receiving more than 30% of the prescribed dose and the mean lung dose compared to the standard plan. However, the standard plan leads to a better homogeneity within the CTV. The results for the left-sided thorax wall are similar but also the dose to the heart is reduced comparing MERT to the standard treatment plan. For the parotid case, MERT leads to lower doses for almost all OARs but to a less homogeneous dose distribution for the PTV when compared to a standard plan. For all cases, the weight optimization successfully minimized the differences between the optimal and the deliverable dose distribution. CONCLUSIONS A beamlet based DAO using multiple beam angles is implemented and successfully tested for an idealized water phantom geometry and clinical situations.

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Purpose The radiolanthanide 161Tb (T 1/2 = 6.90 days, Eβ− av = 154 keV) was recently proposed as a potential alternative to 177Lu (T 1/2 = 6.71 days, Eβ− av = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare 161Tb and 177Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). Methods 161Tb-cm09 and 177Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo 161Tb-cm09 and 177Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using 99mTc-dimercaptosuccinic acid (DMSA). Results To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for 161Tb-cm09 (IC50 ~0.014 MBq/ml and ~2.53 MBq/ml) compared to 177Lu-cm09 (IC50 ~0.063 MBq/ml and ~4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies 161Tb-cm09 reduced tumour growth more efficiently than 177Lu-cm09. These findings were in line with the higher absorbed tumour dose for 161Tb-cm09 (3.3 Gy/MBq) compared to 177Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Conclusion Compared to 177Lu-cm09 we demonstrated equal imaging features for 161Tb-cm09 but an increased therapeutic efficacy for 161Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical studies using other tumour-targeting radioconjugates are clearly necessary to draw final conclusions about the future clinical perspectives of 161Tb.

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OBJECTIVE: To develop a behavioural observation method to simultaneously assess distractors and communication/teamwork during surgical procedures through direct, on-site observations; to establish the reliability of the method for long (>3 h) procedures. METHODS: Observational categories for an event-based coding system were developed based on expert interviews, observations and a literature review. Using Cohen's κ and the intraclass correlation coefficient, interobserver agreement was assessed for 29 procedures. Agreement was calculated for the entire surgery, and for the 1st hour. In addition, interobserver agreement was assessed between two tired observers and between a tired and a non-tired observer after 3 h of surgery. RESULTS: The observational system has five codes for distractors (door openings, noise distractors, technical distractors, side conversations and interruptions), eight codes for communication/teamwork (case-relevant communication, teaching, leadership, problem solving, case-irrelevant communication, laughter, tension and communication with external visitors) and five contextual codes (incision, last stitch, personnel changes in the sterile team, location changes around the table and incidents). Based on 5-min intervals, Cohen's κ was good to excellent for distractors (0.74-0.98) and for communication/teamwork (0.70-1). Based on frequency counts, intraclass correlation coefficient was excellent for distractors (0.86-0.99) and good to excellent for communication/teamwork (0.45-0.99). After 3 h of surgery, Cohen's κ was 0.78-0.93 for distractors, and 0.79-1 for communication/teamwork. DISCUSSION: The observational method developed allows a single observer to simultaneously assess distractors and communication/teamwork. Even for long procedures, high interobserver agreement can be achieved. Data collected with this method allow for investigating separate or combined effects of distractions and communication/teamwork on surgical performance and patient outcomes.