Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the development of a BP wafer for a novel therapeutic strategy for treating GBM invasion and increasing survival in clinical subjects.

A survey of the attitudes of scientists toward xenotransplantation in Taiwan.

This study examined the attitudes of scientists in Taiwan's leading animal research institution toward xenotransplantation. The aim was primarily to evaluate the opinions of professionals in the biomedical field on key issues including ethical moral, legal, and regulatory issues raised by the biotechnology. A secondary objective was to identify potential factors that influenced opinions. A questionnaire-based survey was used to evaluate opinions. A test for internal consistency of the questionnaires to sample of 91 scientists was performed as well as a principal component analysis. We evaluated associations between variables using the nonparametric Kruskal-Wallis test. Among the subjects 85.2% thought that xenotransplantation can be more beneficial than harmful to human society and 94.3% believed that it is important to develop xenotransplantation. Also, 97.8% of participants believed that legislative guidelines should be adopted to regulate research in biotechnology. Gender was an influencing factor, whereas, variables such as religion, marital status, and age did not have obvious effects. Further studies on the general public are needed to detect other factors and to examine the attitude of nonprofessionals toward xenotransplantation.

Controlled release of nalbuphine propionate from biodegradable microspheres: in vitro and in vivo studies.

The objective of this work was to assess the in vitro characteristics, in vivo pharmacokinetics and in vivo pharmacodynamics of nalbuphine propionate (NAP)-loaded microspheres. An oil-in-water solvent evaporation method was used to incorporate NAP into poly (d,l-lactide-co-glycolide) (PLGA)-based microspheres. The morphology of the microspheres were evaluated using scanning electron microscopy which showed a spherical shape with smooth surface. A prolonged in vitro drug release profile was observed, with approximately 71.1% of incorporated drug released in 96 h. The release profile fit well to the Baker and Lonsdale's spherical matrix model, suggesting the release of NAP from microspheres was consistent with a diffusion mechanism. The in vivo pharmacokinetic studies after subcutaneous injection of NAP-loaded microsphere showed a sustained plasma nalbuphine (NA)-time profile, with 100% relative bioavailability comparing to the AUC obtained after intravenous injection. The in vitro release pattern correlated well with the in vivo pharmacokinetic profile. The pharmacodynamic studies evaluated using paw pressure model also showed a prolonged pharmacological response after injection of microspheres. A linear correlation between the percent analgesic effect and the logarithm of plasma NA concentration was obtained, suggesting the pharmacological response can be reflected by plasma drug concentration. This correlation may be utilized for evaluating the pharmacological responses of various NA and its prodrug-based formulations with known plasma NA concentrations.

Stair-step artifacts with single versus multiple detector-row helical CT.

PURPOSE: To compare the effects of acquisition parameters on the magnitude and appearance of artifacts between single and multiple detector-row helical computed tomography (CT). MATERIALS AND METHODS: A cylindric (12.7 x 305.0-mm) acrylic rod inclined 45 degrees relative to the z axis was scanned at the isocenter and 100 mm from the isocenter with single detector-row (single-channel) helical CT (beam width, 1-10 mm; pitch, 1.0, 2.0, or 3.0) and multiple detector-row (four-channel) helical CT (detector width, 1. 25, 2.5, 3.75, and 5 mm; pitch, 0.75 or 1.5). The SD of radius measurements along the rod (SD(r)) was used to quantify artifacts in all 72 data sets and to analyze their frequency patterns. Volume-rendered images of the data sets were ranked by six independent and blinded readers; findings were correlated with acquisition parameters and SD(r) measurements. RESULTS: SD(r) was smaller in four- than in single-channel helical CT for any given table increment (TI). In single-channel helical CT, SD(r) increased linearly with beam width and geometrically with pitch. In four-channel helical CT, SD(r) measurements were directly proportional to the TI, regardless of the detector width and pitch combination used. Off-center object position on average increased SD(r) by a factor of 1.6 for single-channel helical CT and by a factor of 2.0 for four-channel helical CT. Subjective rankings of image quality correlated excellently with SD(r) (Spearman r = 0.94, P <.001). CONCLUSION: Artifacts are quantitatively and subjectively smaller with four- compared with single-channel helical CT for any given TI.

Reconstruction algorithm for polychromatic CT imaging: application to beam hardening correction.

This paper presents a new reconstruction algorithm for both single- and dual-energy computed tomography (CT) imaging. By incorporating the polychromatic characteristics of the X-ray beam into the reconstruction process, the algorithm is capable of eliminating beam hardening artifacts. The single energy version of the algorithm assumes that each voxel in the scan field can be expressed as a mixture of two known substances, for example, a mixture of trabecular bone and marrow, or a mixture of fat and flesh. These assumptions are easily satisfied in a quantitative computed tomography (QCT) setting. We have compared our algorithm to three commonly used single-energy correction techniques. Experimental results show that our algorithm is much more robust and accurate. We have also shown that QCT measurements obtained using our algorithm are five times more accurate than that from current QCT systems (using calibration). The dual-energy mode does not require any prior knowledge of the object in the scan field, and can be used to estimate the attenuation coefficient function of unknown materials. We have tested the dual-energy setup to obtain an accurate estimate for the attenuation coefficient function of K2 HPO4 solution.

Modeling of polychromatic attenuation using computed tomography reconstructed images.

This paper presents a procedure for estimating an accurate model of the CT imaging process including spectral effects. As raw projection data are typically unavailable to the end-user, we adopt a post-processing approach that utilizes the reconstructed images themselves. This approach includes errors from x-ray scatter and the nonidealities of the built-in soft tissue correction into the beam characteristics, which is crucial to beam hardening correction algorithms that are designed to be applied directly to CT reconstructed images. We formulate this approach as a quadratic programming problem and propose two different methods, dimension reduction and regularization, to overcome ill conditioning in the model. For the regularization method we use a statistical procedure, Cross Validation, to select the regularization parameter. We have constructed step-wedge phantoms to estimate the effective beam spectrum of a GE CT-I scanner. Using the derived spectrum, we computed the attenuation ratios for the wedge phantoms and found that the worst case modeling error is less than 3% of the corresponding attenuation ratio. We have also built two test (hybrid) phantoms to evaluate the effective spectrum. Based on these test phantoms, we have shown that the effective beam spectrum provides an accurate model for the CT imaging process. Last, we used a simple beam hardening correction experiment to demonstrate the effectiveness of the estimated beam profile for removing beam hardening artifacts. We hope that this estimation procedure will encourage more independent research on beam hardening corrections and will lead to the development of application-specific beam hardening correction algorithms.

Longitudinal sampling and aliasing in spiral CT.

Although analyses of in-plane aliasing have been done for conventional computed tomography (CT) images, longitudinal aliasing in spiral CT has not been properly investigated. We propose a mathematical model of the three-dimensional (3-D) sampling scheme in spiral CT and analyze its effects on longitudinal aliasing. We investigated longitudinal aliasing as a function of the helical-interpolation algorithm, pitch, and reconstruction interval using CT simulations and actual phantom scans. Our model predicts, and we verified, that for a radially uniform object at the isocenter, the spiral sampling scheme results in spatially varying cancellation of the aliased spectral islands which, in turn, results in spatially varying longitudinal aliasing. The aliasing is minimal at the scanner isocenter, but worsens with distance from it and rapidly becomes significant. Our results agree with published results observed at the isocenter of the scanner and further provide new insight into the aliasing conditions at off-isocenter locations with respect to the pitch, interpolation algorithm, and reconstruction interval. We conclude that longitudinal aliasing at off-isocenter locations can be significant, and that its magnitude and effects cannot be predicted by measurements made only at the scanner isocenter.

Spatially varying longitudinal aliasing and resolution in spiral computed tomography.

Spiral computed tomography (CT) has revolutionized conventional CT as a truly three-dimensional imaging modality. A number of studies aimed at evaluating the longitudinal resolution in spiral CT have been presented, but the spatially varying nature of the longitudinal resolution in spiral CT has been largely left undiscussed. In this paper, we investigate the longitudinal resolution in spiral CT as affected by the spatially varying longitudinal aliasing. We propose the treatment of aliasing as a signal dependent, additive noise, and define a new image quality parameter, the contrast-to-aliased-noise ratio (CNaR), that relates to possible image degradation or loss of resolution caused by aliasing. We performed CT simulations and actual phantom scans using a resolution phantom consisting of sequences of spherical beads of different diameters, extending along the longitudinal axis. Our results show that the off-isocenter longitudinal resolution differs significantly from the longitudinal resolution at the isocenter and that the CNaR decreases with distance from the isocenter, and is a function of pitch and the helical interpolation algorithm used. The longitudinal resolution was observed to worsen with decreasing CNaR. We conclude that the longitudinal resolution in spiral CT is spatially varying, and can be characterized by the CNaR measured at the transaxial location of interest.

A new frame-based registration algorithm.

This paper presents a new algorithm for frame registration. Our algorithm requires only that the frame be comprised of straight rods, as opposed to the N structures or an accurate frame model required by existing algorithms. The algorithm utilizes the full 3D information in the frame as well as a least squares weighting scheme to achieve highly accurate registration. We use simulated CT data to assess the accuracy of our algorithm. We compare the performance of the proposed algorithm to two commonly used algorithms. Simulation results show that the proposed algorithm is comparable to the best existing techniques with knowledge of the exact mathematical frame model. For CT data corrupted with an unknown in-plane rotation or translation, the proposed technique is also comparable to the best existing techniques. However, in situations where there is a discrepancy of more than 2 mm (0.7% of the frame dimension) between the frame and the mathematical model, the proposed technique is significantly better (p < or = 0.05) than the existing techniques. The proposed algorithm can be applied to any existing frame without modification. It provides better registration accuracy and is robust against model mis-match. It allows greater flexibility on the frame structure. Lastly, it reduces the frame construction cost as adherence to a concise model is not required.