Field map estimation with a region growing scheme for iterative 3-point water-fat decomposition.

Robust fat suppression techniques are required for many clinical applications. Multi-echo water-fat separation methods are relatively insensitive to B(0) field inhomogeneity compared to the fat saturation method. Estimation of this field inhomogeneity, or field map, is an essential and important step, which is well known to have ambiguity. For an iterative water-fat decomposition method recently proposed, ambiguities still exist, but are more complex in nature. They were studied by analytical expressions and simulations. To avoid convergence to incorrect field map solutions, an initial guess closer to the true field map is necessary. This can be achieved using a region growing process, which correlates the estimation among neighboring pixels. Further improvement in stability is achieved using a low-resolution reconstruction to guide the selection of the starting pixels for the region growing. The proposed method was implemented and shown to significantly improve the algorithm's immunity to field inhomogeneity.     

Spiral magnetic resonance coronary angiography--direct comparison of 1.5 Tesla vs. 3 Tesla.

BACKGROUND: MR coronary angiography (MRCA) has been demonstrated successfully at 3 Tesla (T). However, the advantages remain unclear. No systematic comparison of MRCA between 1.5 T and 3 T has been performed. Therefore, anatomic coverage, image quality, signal-to-noise ratio (SNR), contrast-to-noise ration (CNR), and susceptibility artifacts were compared in 23 subjects. METHODS AND RESULTS: Identical real-time (RT) and high-resolution (HR) sequences were implemented on the GE 1.5 T (Signa Twinspeed) and 3.0 T (Signa VH/i) whole body systems (GE, Milwaukee, WI). Both scanners were equipped with high-performance gradient systems capable of 40 mT/m peak amplitude and 150 mT/m/ms slew rate. Real-time localization of the coronary arteries was followed by a cardiac-gated, breath-hold HR sequence. Twenty-three subjects were recruited consecutively and underwent both 3 T and 1.5 T MRCA within one week. Coronary coverage based on the number of coronary segments visualized, image quality using a grading scale, SNR, CNR, and presence of susceptibility artifacts were analyzed. A significant improvement in SNR (47%), CNR (30%), and image quality were seen in 3 T. However, a significant increase in susceptibility artifacts was also noted. CONCLUSION: MRCA at 3 T significantly improves SNR, CNR, and image quality at the expense of susceptibility artifacts. Further optimization of the imaging parameters at 3 T may facilitate clinical implementation of MRCA.     

The role of internal pilot studies in increasing the efficiency of clinical trials

Investigators often design clinical trials without knowing precisely the values of such necessary parameters as the variances or the event rates in the control group. In order to determine reasonable values for such parameters, they may design a small pilot study external to the main trial. In this paper we propose designs, which we term internal pilot studies, that designate a portion of the main trial as a pilot phase. At the end of the internal pilot study, the investigators recompute preselected parameters and recalculate required sample size. The study then proceeds with the modifications dictated by the internal pilot. Final analyses of the results incorporate all data, disregarding the fact that part of the data came from a pilot phase. As one example of this type of design, we consider a study to compare two normally distributed means. By simulation, we show a numerical example for which the effect of the procedure on the alpha-level is negligible, but the potential gain in power considerable. We urge considering a similar approach for a number of types of endpoints.     

Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels

Serum mast cell tryptase levels are used as a diagnostic criterion and surrogate marker of disease severity in mastocytosis. Approximately 29% of the healthy population lacks alpha tryptase genes; however, it is not known whether lack of alpha tryptase genes leads to variability in tryptase levels or impacts on disease severity in mastocytosis. We have thus analyzed tryptase haplotype in patients with mastocytosis, computing correlations between haplotype and plasma total and mature tryptase levels; and disease category. We found: (1) the distribution of tryptase haplotype in patients with mastocytosis appeared consistent with Hardy-Weinberg equilibrium and the distribution in the general population; (2) the disease severity and plasma tryptase levels were not affected by the number of alpha or beta tryptase alleles in this study; and (3) information about the tryptase haplotype did not provide any prognostic value about the severity of disease. Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration.     

Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions

Previously we have shown that in vitro-packaged simian virus 40 (SV40) pseudovirions (IVPs) are an efficient delivery system for supercoiled DNA plasmids of up to 17.7 kb, with or without SV40 sequences. RNA interference (RNAi) is a naturally occurring gene-silencing mechanism mediated by small double-stranded RNA molecules (small interfering RNAs, siRNAs). This study demonstrates the first use of SV40 pseudovirions to deliver into human cells both principal types of RNAi effector molecules: plasmid-expressed short hairpin RNAs (shRNAs) and synthetic siRNAs. We first established the ability of human lymphoblastoid cells to support RNAi, using sequential transduction of .45 cells with packaged plasmid DNA expressing the green fluorescent protein (IVP-GFP), and an shRNA corresponding to the GFP (IVP-shGFP). SV40 mediates DNA transfer of nucleic acid to the cytoplasm, where RNAi-associated cleavage of mRNA principally occurs. Using SV40 pseudovirions, siRNA-mediated RNAi was observed in both .45 cells, after sequential transduction of IVP-GFP and IVP-packaged siRNAs corresponding to GFP (IVP-siGFP), and in HeLa cells stably expressing a GFP transduced with IVP-siGFP. Our findings indicate that SV40 pseudovirions may be a useful addition to the delivery systems currently being used for the transfer of RNAi effector molecules.     

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.     

Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men.