PET imaging-based evaluation of aerosol drugs and their delivery devices: nasal and pulmonary studies

Three-dimensional (3-D) positron emission tomography (PET) imaging of inhaled radiolabeled aerosol in the nasal or pulmonary regions provides an in vivo measurement of drug distribution using the drug itself as the tracer. Repeated or dynamic PET scans over the time after inhalation provides us with further information about the fate of the deposited drug. These quantitative measurements are sufficient to describe the performance of a drug or device and they are obtained in a noninvasive fashion, which cannot be achieved by using any other methods. Using this PET-imaging paradigm, we conducted a sequence of drug studies to evaluate the performance of aerosol drugs and delivery devices; to compare the performance of similar drugs from different manufacturers; to assess the similarity between different formulations and propellants for the same drug; to appraise delivery devices such as spacers and nebulizers, etc. This paper reviews only the imaging and data analysis techniques developed for the above-mentioned studies that include multi-modality image registration, region definition and region-based data analysis, and nonregion-based data analysis. We separated the techniques into nasal and pulmonary studies because of the uniqueness of each group. Specific drugs or devices are not identified and no result about drug performance is given because the imaging and data analysis methodology, which is the focus of this paper, applies to all these studies regardless of the drugs or their delivery devices. The quantitative data are used as the scientific basis for evaluation although we also developed visualization techniques to enhance the results drawn from the data.     

Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation

Efficient and safe drug delivery across the blood‐brain barrier (BBB) remains one of the major challenges of biomedical and (nano‐) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)‐based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO‐MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non‐invasive R ₂*‐based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R ₂* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)‐dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.     

金属沾污对超薄栅氧(2. 5nm)特性的影响

采用可控的金属沾污程序 ,最大金属表面浓度控制在 10 1 2 cm- 2数量级 ,来模拟清洗工艺最大可能金属沾污表面浓度 .利用斜坡电流应力和栅注入方式测量本征电荷击穿来评估超薄栅氧特性和金属沾污效应 .研究了金属锆和钽沾污对超薄栅氧完整性的影响 .实验结果表明金属锆沾污对超薄栅氧完整性具有最严重危害 ;金属钽沾污的栅氧发生早期击穿现象 ,而金属铝沾污对超薄栅氧完整性没有明显影响 .     

A stochastic continuation approach to piecewise constant reconstruction.

We address the problem of reconstructing a piecewise constant 3-D object from a few noisy 2-D line-integral projections. More generally, the theory developed here readily applies to the recovery of an ideal n-D signal (n > or =1) from indirect measurements corrupted by noise. Stabilization of this ill-conditioned inverse problem is achieved with the Potts prior model, which leads to a challenging optimization task. To overcome this difficulty, we introduce a new class of hybrid algorithms that combines simulated annealing with deterministic continuation. We call this class of algorithms stochastic continuation (SC). We first prove that, under mild assumptions, SC inherits the finite-time convergence properties of generalized simulated annealing. Then, we show that SC can be successfully applied to our reconstruction problem. In addition, we look into the concave distortion acceleration method introduced for standard simulated annealing and we derive an explicit formula for choosing the free parameter of the cost function. Numerical experiments using both synthetic data and real radiographic testing data show that SC outperforms standard simulated annealing.     

在双镶嵌铜互联中O.13微米器件生成用的基于PVD和ALD阻挡层的先进技术

1. Introduction The requirement of minimal bottom coverageand thick sidewall coverage for PVD-based films forlow via resistance and improved stress migration isnot easy to achieve with traditional depositionmethods. Modern I-PVD techniques give high bot-tom coverage, due to the ionized component of thedeposition flux. Sidewall coverage tends to be low,which is mainly due to off-normal deposition fluxand a less than unity sticking coefficient.     

A versatile wavelet domain noise filtration technique for medical imaging

In this paper, we propose a robust wavelet domain method for noise filtering in medical images. The proposed method adapts itself to various types of image noise as well as to the preference of the medical expert; a single parameter can be used to balance the preservation of (expert-dependent) relevant details against the degree of noise reduction. The algorithm exploits generally valid knowledge about the correlation of significant image features across the resolution scales to perform a preliminary coefficient classification. This preliminary coefficient classification is used to empirically estimate the statistical distributions of the coefficients that represent useful image features on the one hand and mainly noise on the other. The adaptation to the spatial context in the image is achieved by using a wavelet domain indicator of the local spatial activity. The proposed method is of low complexity, both in its implementation and execution time. The results demonstrate its usefulness for noise suppression in medical ultrasound and magnetic resonance imaging. In these applications, the proposed method clearly outperforms single-resolution spatially adaptive algorithms, in terms of quantitative performance measures as well as in terms of visual quality of the images.     

In Situ Scanning Electron Microscopy Observation of Growth Kinetics and Catalyst Splitting in Vapor–Liquid–Solid Growth of Nanowires

In situ observations during vapor–liquid–solid (VLS) growth of semiconductor nanowires in the chamber of an environmental scanning electron microscope (ESEM) are reported. For nanowire growth, a powder mixture of CdS and ZnS is used as a source material and silver nanoparticles as a metal catalyst. Through tracing growth kinetics of nanowires, it is found that nanowires with a relatively bigger catalyst droplet on the tip grow faster. Intriguingly, it is also found that the growth of nanowires can involve catalyst splitting: while the majority of catalyst remains at the nanowire tip and continues facilitating the growth, a portion of it is removed from the tip due to the splitting. It remains attached to the nanowire at the position where the splitting occurred and subsequently induces the growth of a nanowire branch. As far as it is known, this is the first time that catalyst splitting is revealed experimentally in situ. It is proposed that the instability of catalyst droplet caused by the volume increase is the main reason for the splitting. It is believed that in situ growth inside the ESEM can largely enrich our understanding on the metal‐catalyzed VLS growth kinetics, which may open up more opportunities for morphology‐controlled synthesis of 1D semiconductor nanowires in future study.     

Building an index of activity of inhabitants from their activity on the residential electrical power line

In the framework of context awareness within the home, our team is currently assessing the unobtrusive detection of inhabitants' activity through the monitoring of their use and consumption of electricity. The objective is to develop a system for the remote monitoring of large populations of elderly people living independently at home. To be readily deployable on the field, such a system must be minimally intrusive both for the home environment and for the field professionals (paramedics and social workers) visiting the patients at home. We carried out two successive field experiments to evaluate and to improve our system designed to deliver a single index of daily activity. The first experiment involved 13 elderly persons over a nine-month period (84,240 h data recorded) and the second one 12 elderly over six months (51,840 h). We evaluated both the relevance of the index and the acceptability of the system as a whole. We discovered that electrical activity is a kind of unique "signature" of each person's activity. Moreover, this profile provides unexpected information on the health status of the subject. We confirmed that the system was unobtrusive and well accepted both by the subjects and by the professionals involved. Our unique index of activity, and its trend over time, can provide timely information to the professionals on the patient.     

Computerized indoor radio channel estimation using ray tracing

This paper describes a computer tool for site specific indoor radio channel characterization. The behavior of the electromagnetic fields associated with a base station and a portable radio unit is simulated by combining approximate geometric optics and ray tracing techniques. Given a building plan and the transmitter/receiver locations, the set of all[attenuation / time delay /phase] vectors, each representing an electromagnetic propagation path between transmitter and receiver, is computed using ray shooting techniques to generate the channel wideband impulse response. The model takes into account specular reflection and transmission. Linear polarization and various antenna patterns can be simulated as well. The simulated results are shown to correlate well with experimental data. The computer tool can be used to provide estimates of the coverage of a base station and of the channel quality.