Grid-free interactive and automated data processing for MR chemical shift imaging data

Purpose  

Today’s available chemical shift imaging (CSI) analysis tools are based on Fourier transform of the entire data set prior to interactive display. This strategy is associated with limitations particularly when arbitrary voxel positions within a 3D spatial volume are needed by the user. In this work, we propose and demonstrate a processing-resource-efficient alternative strategy for both interactive and automated CSI data processing up to three spatial dimensions.     

Definition of a diagnostic score of malignant hyperthermia using P-31 magnetic resonance spectroscopy

OBJECTIVES: To assess the metabolic muscular disorders associated with malignant hyperthermia (MH) using 31-P MRS, in order to develop a diagnostic tool for MH. STUDY DESIGN: Retrospective analysis of a series of case. PATIENTS: Group of 39 subjects, including 13 MH susceptible (MHS), and 26 not susceptible (MHN) members of recognized MHS families, according to the results of the in vitro contracture tests. METHODS: Each subject underwent two protocols, both including rest, exercise and recovery periods. Exercise was performed successively under aerobic and ischaemic conditions. RESULTS AND DISCUSSION: A significant early acidosis was recorded for the MHS group under both conditions of exercise (normoxia and ischaemia). However, the sensitivity of this parameter (77%) was not high enough to be considered as discriminant. Therefore a MRS score has been defined, corresponding to the sum of metabolic anomalies (acidosis, anomalies in PCr tum-over and in ATP or phosphomonoesters concentrations) recorded throughout both protocols. This score provided satisfactory results for both sensitivity (93%) and specificity (93%). CONCLUSION: 31-P MRS can act as a reliable diagnostic tool for MH.     

Use of immunoaffinity columns for clean-up of diarrhetic toxins (okadaic acid and dinophysistoxins) extracts from shellfish prior to their analysis by HPLC/fluorimetry

Diarrhetic Shellfish Poisoning (DSP) is a severe gastro-intestinal disease caused by consumption of seafood contaminated by microalgal toxins, mainly okadaic acid (OA) and structurally related toxins, dinophysistoxins (DTXs). Regulatory monitoring is generally based on rodent bioassays which, however, present some technical and ethical disadvantages. The most promising technique of analysis of these toxins involves an HPLC separation with spectrofluorimetric detection after derivatization of the toxins with a fluorescent reagent. The lack of specificity of the extraction procedure (liquid-liquid partition), and the presence of interfering compounds in the matrix, does not allow the determination and the quantification of low amounts of toxins in seafood. In this paper, the authors report the development and the characterization of immunoaffinity columns (IAC), which were elaborated using anti-okadaic acid monoclonal antibodies, for a specific retention of the OA group of toxins. The coupling yield and the stability of these columns were investigated as well as their capacity to remove interfering compounds. Cross-reactivity was observed between the antibodies and the DTX-1 and the DTX-2, allowing the detection of the different toxins in a single analysis. Different spiked (1mugOA/ g) or naturally-contaminated (mussel digestive gland: 2mugOA/g; algae: 165mugOA/g) matrices were tested. The recovery for OA varied from 55 to 95% according to the matrices. The IAC purification was then included as a step of a global [IAC/HPLC/spectrofluorimetric detection] method and the performance of the method was evaluated. Estimations of the linearity and the accuracy (percentages of the presumptive response for OA in the range + 101% to + 114%) were satisfactory in accordance with the method validation criteria.     

Synthesis of anti-microtubule biaryls and preliminary evaluation as vascular-disrupting agents

A series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki–Miyaura coupling and Brønsted‐acid‐mediated cyclodehydration as key steps. The vascular‐disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of microtubule assembly, antiproliferative activity against cancer cell lines and normal endothelial cells, modification of endothelial cell morphology, and disruption of endothelial cell cords. Two of these compounds showed promising activities in these assays, with profiles similar to that of the reference drug NAC and markedly different from that of colchicine. Altogether, these results show that dibenzoxepines represent promising new leads for the development of more selective vascular‐disrupting agents.     

Automated target preparation for microarray-based gene expression analysis

DNA microarrays have rapidly evolved toward a platform for massively paralleled gene expression analysis. Despite its widespread use, the technology has been criticized to be vulnerable to technical variability. Addressing this issue, recent comparative, interplatform, and interlaboratory studies have revealed that, given defined procedures for "wet lab" experiments and data processing, a satisfactory reproducibility and little experimental variability can be achieved. In view of these advances in standardization, the requirement for uniform sample preparation becomes evident, especially if a microarray platform is used as a facility, i.e., by different users working in the laboratory. While one option to reduce technical variability is to dedicate one laboratory technician to all microarray studies, we have decided to automate the entire RNA sample preparation implementing a liquid handling system coupled to a thermocycler and a microtiter plate reader. Indeed, automated RNA sample preparation prior to chip analysis enables (1) the reduction of experimentally caused result variability, (2) the separation of (important) biological variability from (undesired) experimental variation, and (3) interstudy comparison of gene expression results. Our robotic platform can process up to 24 samples in parallel, using an automated sample preparation method that produces high-quality biotin-labeled cRNA ready to be hybridized on Affymetrix GeneChips. The results show that the technical interexperiment variation is less pronounced than with manually prepared samples. Moreover, experiments using the same starting material showed that the automated process yields a good reproducibility between samples.     

巴黎地区轨道交通系统

Greater Paris is famous for its extensive metro and RER（express rail）system.By the end of 2006,there were 14 metro lines in Paris as illustrated in Figure 1,and 5 RER lines as illustrated in Figure 2.     

Investigation of metabolic myopathies by P-31 MRS using a standardized rest-exercise-recovery protocol: a survey of 800 explorations

A standardized P-31 magnetic resonance spectroscopy (MRS) protocol for the exploration of muscle metabolism by P-31 MRS in trained and untrained subjects as well as in patients with intolerance to exercise has been developed to meet the specific requirements of a clinical environment. This protocol is based on a short-term intense exercise which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been established to characterize the normal metabolic response to the protocol. As a matter of fact, the comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying diseases. Deviations from normality can be directly interpreted in terms of specific pathologies in some favourable cases. In most cases, P-31 MRS provides valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. For malignant and exertional hyperthermias, P-31 MRS constitutes a diagnostic tool with 100% sensitivity, as compared to contracture tests. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. This procedure is already approved for reimbursement in the public hospital system in Marseille, France.