MRI strain imaging of the carotid artery: Present limitations and future challenges

Rupture of atherosclerotic plaques in the carotid artery is a main cause of stroke. Current diagnostics are not sufficient to identify all rupture-prone plaques, and studies have shown that biomechanical factors improve current plaque risk assessment. Strain imaging may be a valuable contribution to this risk assessment. MRI is a versatile imaging technique that offers various methods that are capable of measuring tissue strain. In this review, MR imaging techniques with displacement (DENSE), velocity (PC MRI), or strain (SENC) encoding protocols are discussed, together with post-processing techniques based on time-resolved MRI data. Although several MRI techniques are being developed to improve time-resolved MR imaging, current technical limitations related to spatial and temporal resolutions render MRI strain imaging currently unfit for carotid plaque strain evaluation.     

In vivo three-dimensional intervertebral kinematics of the subaxial cervical spine during seated axial rotation and lateral bending via a fluoroscopy-to-CT registration approach

Accurate measurement of the coupled intervertebral motions is helpful for understanding the etiology and diagnosis of relevant diseases, and for assessing the subsequent treatment. No study has reported the in vivo, dynamic and three-dimensional (3D) intervertebral motion of the cervical spine during active axial rotation (AR) and lateral bending (LB) in the sitting position. The current study fills the gap by measuring the coupled intervertebral motions of the subaxial cervical spine in ten asymptomatic young adults in an upright sitting position during active head LB and AR using a volumetric model-based 2D-to-3D registration method via biplane fluoroscopy. Subject-specific models of the individual vertebrae were derived from each subject’s CT data and were registered to the fluoroscopic images for determining the 3D poses of the subaxial vertebrae that were used to obtain the intervertebral kinematics. The averaged ranges of motion to one side (ROM) during AR at C3/C4, C4/C5, C5/C6, and C6/C7 were 4.2°, 4.6°, 3.0° and 1.3°, respectively. The corresponding values were 6.4°, 5.2°, 6.1° and 6.1° during LB. Intervertebral LB (ILB) played an important role in both AR and LB tasks of the cervical spine, experiencing greater ROM than intervertebral AR (IAR) (ratio of coupled motion (IAR/ILB): 0.23–0.75 in LB, 0.34–0.95 in AR). Compared to the AR task, the ranges of ILB during the LB task were significantly greater at C5/6 (p=0.008) and C6/7 (p=0.001) but the range of IAR was significantly smaller at C4/5 (p=0.02), leading to significantly smaller ratios of coupled motions at C4/5 (p=0.0013), C5/6 (p<0.001) and C6/7 (p=0.0037). The observed coupling characteristics of the intervertebral kinematics were different from those in previous studies under discrete static conditions in a supine position without weight-bearing, suggesting that the testing conditions likely affect the kinematics of the subaxial cervical spine. While C1 and C2 were not included owing to technical limitations, the current results nonetheless provide baseline data of the intervertebral motion of the subaxial cervical spine in asymptomatic young subjects under physiological conditions, which may be helpful for further investigations into spine biomechanics.     

2013 年江苏省药品注册管理工作报告

通过相关数据资料的统计、对比,2013 年对江苏省药品注册管理工作进行总结性回顾,以促进全省药品注册管理能力的提升,研究制订出更符合江苏实际的药品注册管理工作政策和措施。     

中国抗体药物产业现状与发展前景

我国抗体药物起步晚,研发与生产技术与国际水平相比尚有一定的差距,但我国抗体药物产业发展迅速,国家政策支持以及研发投入力度较大,目前已取得一定的成果,市场潜力巨大。根据近年来国内相关文献报道以及CFDA、CDE网站的数据库,对我国抗体药物的上市、注册、审批情况以及产业化现状、重点研发企业、发展方向等方面进行归纳总结。综述了我国抗体药物的研究进展及发展前景,为生物制药企业及从事生产研发的科研人员提供了参考依据。     

Separation and characterisation of light scattering transients from rod outer segments of vertebrate photoreceptors: design and performance of a Multi Angle Flash Photolysis Apparatus (MAFPA)

A device was built for the simple computer-controlled routine determination of the angular dependence of light scattering transients obtained from biological material. It was called Multi Angle Flash Photolysis Apparatus (MAFPA). The MAFPA allows the simultaneous registration of rapid, light-induced light scattering transients at eight scattering angles between 0 degree and 28 degrees. In typical applications changes in scattered light intensity as small as delta I/I = 4 X 10(-5) can be resolved at scattering angles less than 24 degrees, while at 28 degrees the resolution drops to delta I/I = 2 X 10(-4). The time resolution is 32 microseconds. The MAFPA was designed for high accuracy, ease of use and ruggedness. It is made from relatively inexpensive parts and can be copied fairly easily by a good machine/electronics shop. In this communication we describe the design of the MAFPA and how it was used for the characterisation of four structurally distinct light-induced light scattering signals from photoreceptor rod outer segments. These signals are known as P (or binding) signal, G- (or dissociation) signal, N (or rhodopsin) signal and as the ATP-dependent signal AL. The signals have been separated by means of their different angular dependence, their different saturation behavior and nucleotide requirement. A great number of detailed studies will have to be carried out before one can fully understand the physical and biochemical origin of these signals. At this point, however, it can be stated that the so-called 'dissociation signal', showing an angular dependence indicative of a change in refractive index or scattering mass, is not merely an inversion of the preceding 'binding signal', the latter clearly reflecting a gross structural change, i.e. a shrinkage of the disks. Moreover, there are conditions where P signals are observed to persist even after the completion of the subsequent dissociation signals. The two remaining signals N and AL show a pronounced angular dependence which is not easily interpreted. The fact that both exhibit a maximal amplitude at relatively small angles seems to indicate the participation of rather large structural domains.     

Voxel-based analysis in radiation oncology: A methodological cookbook

Recently, 2D or 3D methods for dose distribution analysis have been proposed as evolutions of the Dose Volume Histogram (DVH) approaches. Those methods, collectively referred to as pixel- or voxel-based (VB) methods, evaluate local dose response patterns and go beyond the organ-based philosophy of Normal Tissue Complication Probability (NTCP) modelling. VB methods have been introduced in the context of radiation oncology in the very last years following the virtuous example of neuroimaging experience. In radiation oncology setting, dose mapping is a suitable scheme to compare spatial patterns of local dose distributions between patients who develop toxicity and who do not.In this critical review, we present the methods that include spatial dose distribution information for evaluating different toxicity endpoints after radiation therapy. The review addresses two main topics. First, the critical aspects in dose map building, namely the spatial normalization of the dose distributions from different patients. Then, the issues related to the actual dose map comparison, i.e. the viable options for a robust VB statistical analysis and the potential pitfalls related to the adopted solutions. To elucidate the different theoretical and technical issues, the covered topics are illustrated in relation to practical applications found in the existing literature.We conclude the overview on the VB philosophy in radiation oncology by introducing new phenomenological approaches to NTCP modelling that accounts for inhomogeneous organ radiosensitivity.     

Challenges and Research Needs for Risk Assessment of Pesticides for Registration in Africa

Risk assessment is necessary for registration and risk management of new pesticides. The aim of this article is to discuss challenges that risk assessors in Africa face when conducting risk assessment of pesticides. Risk assessment requires toxicity assessment, environmental fate studies, and the use of models for occupational, dietary, residential, and environmental exposure assessments. Toxicity studies are very costly with the result that toxicity data used to register pesticides in Africa are often sourced from northern hemisphere countries. Assessors also often use exposure modeling results from the northern hemisphere. This is not an ideal approach as occupational exposure is influenced by agricultural practices, climatic conditions, and other factors. Furthermore, residential exposure models require time-location-activity information, exposure factors, and toxicokinetic rate constants for particular pesticides. Dietary exposure assessment needs accurate and comprehensive local food consumption data. Authorities in African countries should therefore generate the required data, despite these being very costly and tedious. Authorities should also provide guidance on the type of models and standard scenarios for estimating predicted environmental concentrations in various environmental compartments. It is recommended that higher educational institutions in Africa should incorporate risk assessment in general and pesticide toxicity and exposure models in particular in their curricula.     

Automated tracking of stem cell lineages of Arabidopsis shoot apex using local graph matching

Shoot apical meristems (SAMs) of higher plants harbor stem‐cell niches. The cells of the stem‐cell niche are organized into spatial domains of distinct function and cell behaviors. A coordinated interplay between cell growth dynamics and changes in gene expression is critical to ensure stem‐cell homeostasis and organ differentiation. Exploring the causal relationships between cell growth patterns and gene expression dynamics requires quantitative methods to analyze cell behaviors from time‐lapse imagery. Although technical breakthroughs in live‐imaging methods have revealed spatio‐temporal dynamics of SAM‐cell growth patterns, robust computational methods for cell segmentation and automated tracking of cells have not been developed. Here we present a local graph matching‐based method for automated‐tracking of cells and cell divisions of SAMs of Arabidopsis thaliana. The cells of the SAM are tightly clustered in space which poses a unique challenge in computing spatio‐temporal correspondences of cells. The local graph‐matching principle efficiently exploits the geometric structure and topology of the relative positions of cells in obtaining spatio‐temporal correspondences. The tracker integrates information across multiple slices in which a cell may be properly imaged, thus providing robustness to cell tracking in noisy live‐imaging datasets. By relying on the local geometry and topology, the method is able to track cells in areas of high curvature such as regions of primordial outgrowth. The cell tracker not only computes the correspondences of cells across spatio‐temporal scale, but it also detects cell division events, and identifies daughter cells upon divisions, thus allowing automated estimation of cell lineages from images captured over a period of 72 h. The method presented here should enable quantitative analysis of cell growth patterns and thus facilitating the development of in silico models for SAM growth.     

Ecological Risk Assessment Approaches Within the Regulatory Framework

Ecological risk assessment has a short history but a framework similar to human health risk assessment. The Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) played a significant role in the development of the ecological risk process. Data developed and risk procedures used within TSCA and FIFRA have become generally standardized. Fundamental components of the risk process require data on the effects of chemicals in the form of concentration (or dose) — response profiles for species and an exposure profile to quantify the magnitude, spatial and temporal patterns of exposure relevant to significant biological endpoints being studied. Risk characterization generally involves comparing exposure and effects using point estimates (e.g., quotient method) but risk estimation is moving toward a probabilistic approach by comparing distributions of values with more consideration of the sources of uncertainty. Ecological testing guidelines in TSCA and FIFRA are discussed along with the risk characterization process used in each statute.     

Computer-aided hepatic tumour ablation: requirements and preliminary results

Surgical resection of hepatic tumours is not always possible, since it depends on different factors, among which their location inside the liver functional segments. Alternative techniques consist in local use of chemical or physical agents to destroy the tumour. Radio frequency and cryosurgical ablations are examples of such alternative techniques that may be performed percutaneously. This requires a precise localisation of the tumour placement during ablation. Computer-assisted surgery tools may be used in conjunction with these new ablation techniques to improve the therapeutic efficiency, whilst they benefit from minimal invasiveness. This paper introduces the principles of a system for computer-assisted hepatic tumour ablation and describes preliminary experiments focusing on data registration evaluation. To keep close to conventional protocols, we consider registration of pre-operative CT or MRI data to intra-operative echographic data.