Correlation of diffusion tensor tractography and intraoperative macrostimulation during deep brain stimulation for Parkinson disease.

Object The purpose of this study was to investigate whether diffusion tensor imaging (DTI) of the corticospinal tract (CST) is a reliable surrogate for intraoperative macrostimulation through the deep brain stimulation (DBS) leads. The authors hypothesized that the distance on MRI from the DBS lead to the CST as determined by DTI would correlate with intraoperative motor thresholds from macrostimulations through the same DBS lead. Methods The authors retrospectively reviewed pre- and postoperative MRI studies and intraoperative macrostimulation recordings in 17 patients with Parkinson disease (PD) treated by DBS stimulation. Preoperative DTI tractography of the CST was coregistered with postoperative MRI studies showing the position of the DBS leads. The shortest distance and the angle from each contact of each DBS lead to the CST was automatically calculated using software-based analysis. The distance measurements calculated for each contact were evaluated with respect to the intraoperative voltage thresholds that elicited a motor response at each contact. Results There was a nonsignificant trend for voltage thresholds to increase when the distances between the DBS leads and the CST increased. There was a significant correlation between the angle and the voltage, but the correlation was weak (coefficient of correlation [R] = 0.36). Conclusions Caution needs to be exercised when using DTI tractography information to guide DBS lead placement in patients with PD. Further studies are needed to compare DTI tractography measurements with other approaches such as microelectrode recordings and conventional intraoperative MRI-guided placement of DBS leads.

Interobserver and intraobserver variability of the apparent diffusion coefficient in treated malignant hepatic lesions on a 3.0T machine: measurements in the whole lesion versus in the area with the most restricted diffusion.

PURPOSE: To assess the inter/intraobserver variability of apparent diffusion coefficient (ADC) measurements in treated hepatic lesions and to compare ADC measurements in the whole lesion and in the area with the most restricted diffusion (MRDA). MATERIALS AND METHODS: Twenty-five patients with treated malignant liver lesions were examined on a 3.0T machine. After agreeing on the best ADC image, two readers independently measured the ADC values in the whole lesion and in the MRDA. These measurements were repeated 1 month later. The Bland-Altman method, Spearman correlation coefficients, and the Wilcoxon signed-rank test were used to evaluate the measurements. RESULTS: Interobserver variability for ADC measurements in the whole lesion and in the MRDA was 0.17 x 10(-3) mm(2)/s [-0.17, +0.17] and 0.43 x 10(-3) mm(2)/s [-0.45, +0.41], respectively. Intraobserver limits of agreement could be as low as [-0.10, +0.12] 10(-3) mm(2)/s and [-0.20, +0.33] 10(-3) mm(2)/s for measurements in the whole lesion and in the MRDA, respectively. CONCLUSION: A limited variability in ADC measurements does exist, and it should be considered when interpreting ADC values of hepatic malignancies. This is especially true for the measurements of the minimal ADC.

Diffusion-weighted MRI in metastatic gastrointestinal tumours (GIST): a pilot study on the assessment of treatment response in comparison with 18 F-FDG PET/CT

Purpose: To evaluate the clinical potential of diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) mapping for the assessment of gastrointestinal stromal tumour (GIST) response to targeted therapy in comparison with 18F-FDG PET/CT Methods and Materials: Five patients (3 W/2M, aged 56±13 y) with metastatic GIST underwent both a 18F-FDG PET/CT (Discovery LS, GE Healthcare) and a MRI (VIBE T1 Gd, DWI [b = 50,300,600] and ADC mapping) before and after change in therapy. Exams were first analysed blindly and then PET/CT images were coregistered to T1 Gd MR images for lesion detection. SUVmax and ADC were measured for the six largest lesions on MRI. The relationship between SUVmax and ADC was analysed using Spearman's correlation. Results: Altogether, 24 lesions (15 hepatic and 9 non-hepatic) were analysed on both modalities. Three PET/CT lesions (12.5%) were initially not considered on ADC and 4 lesions on the second PET/CT were excluded because of hepatic vascular activity spillover. SUVmax decreased from 7.2±7.7 g/mL to 5.9±5.9 g/mL (P = 0.53) and ADC increased from 1.2x10-3 mm2/s ± 0.4 to 1.4x10-3 mm2/s ± 0.4 (P = 0.07). There was a significant association between SUVmax decrease and ADC increase (rho= -0.64, P = 0.004). Conclusion: Changes in ADC from diffusion-weighted MRI reflect response of 18F-FDG-avid GIST to therapy. The exact diagnostic value of DWI needs to be investigated further, as well as the effect of lesion size and time under therapy before imaging. Furthermore, the proven association between SUVmax and ADC may be useful for the assessment of treatment response in 18F-FDG non-avid GIST.

Functional MRI evaluation of liver tumour response after radiofrequency: short- and mid-term evolution of diffusion parameters

Purpose: To evaluate the short- and mid-term evolutions of the apparent diffusion coefficient of lesions treated with RF, in order to determine if the ADC can be used as a marker of tumour response. Methods and Materials: Twenty patients were treated for a liver malignancy with RF and were examined on a 1.5 T/3.0 T machine with T2, gadolinium-enhanced T1 and diffusion sequences: before treatment (< 1 month), just after treatment (< 1 month) and midterm (3-6 months). The ADC was measured in the whole lesion and in the area with the most restricted diffusion (MRDA). The ROI size was also measured on the diffusion map. The Pearson/ANOVA tests were used. Results: All patients were successfully treated with complete disappearance of CE. The lesional size on T2 showed a negative evolution in time (p < 0.002). The ADC in the whole lesion showed a bell-shaped evolution (increasing just after RF, then decreasing, p = 0.02). The ROI size on the diffusion map followed a similar course (p = 0.01). For the MRDA, such evolutions were also found, but they were not significant. There was a negative correlation between CE and the ADC (p < 0.02) and between the lesional size on T2 and ADC (p = 0.03) in the whole lesion. There were also positive correlations between the ROI size and ADC (p = 0.0008) and between CE and the size on T2 (p = 0.0002). The ADC in MRDA showed some non-significant correlations with other variables. Conclusion: The lesions successfully treated with RF have a clear and predictable evolution in terms of T2 size, CE and ADC.

Man Made Black Holes and Big Bangs: Diffusion and Integration of Scientific Information into Everyday Thinking

Drawing on Social Representations Theory, this study investigates focalisation and anchoring during the diffusion of information concerning the Large Hadron Collider (LHC), the particle accelerator at the European Organisation for Nuclear Research (CERN). We hypothesised that people focus on striking elements of the message, abandoning others, that the nature of the initial information affects diffusion of information, and that information is anchored in prior attitudes toward CERN and science. A serial reproduction experiment with two generations and four chains of reproduction diffusing controversial versus descriptive information about the LHC shows a reduction of information through generations, the persistence of terminology regarding the controversy and a decrease of other elements for participants exposed to polemical information. Concerning anchoring, positive attitudes toward CERN and science increase the use of expert terminology unrelated to the controversy. This research highlights the relevance of a social representational approach in the public understanding of science.

Scalable inference of heterogeneous reaction kinetics from pooled single-cell recordings.

Mathematical methods combined with measurements of single-cell dynamics provide a means to reconstruct intracellular processes that are only partly or indirectly accessible experimentally. To obtain reliable reconstructions, the pooling of measurements from several cells of a clonal population is mandatory. However, cell-to-cell variability originating from diverse sources poses computational challenges for such process reconstruction. We introduce a scalable Bayesian inference framework that properly accounts for population heterogeneity. The method allows inference of inaccessible molecular states and kinetic parameters; computation of Bayes factors for model selection; and dissection of intrinsic, extrinsic and technical noise. We show how additional single-cell readouts such as morphological features can be included in the analysis. We use the method to reconstruct the expression dynamics of a gene under an inducible promoter in yeast from time-lapse microscopy data.

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A Knudsen flow reactor has been used to quantify functional groups on the surface of seven different types of combustion particle samples: 3 amorphous carbons (FS 101, Printex 60, FW 2), 2 flame soots (hexane soot generated from a rich and a lean diffusion flame), and 2 Diesel particles (SRM 2975, Diesel soot recovered from a Diesel particulate filter). The technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. Six probe gases have been selected for the quantification of important functional groups: N(CH3)3 for the titration of acidic sites, NH2OH for carbonyl functions of aldehydes and ketones, CF3COOH and HCl for basic sites of different strength, O3 and NO2 for oxidizable groups. The limit of detection was generally well below 1% of a formal monolayer of adsorbed probe gas. Results obtained with N(CH3)3 were higher for the FW 2 amorphous carbon (post-oxidized sample, according to the manufacturer) and the Diesel particles (between 5.2·10 13 and 5.8·10 13 molecule/cm2), indicating a higher state of oxidation than for the other samples (between 1.3·10 12 and 3.7·10 12 molecule/cm2). The ratio of uptakes of CF3COOH and HCl inferred the presence of basic oxides on the particle surface, owing to the larger stability of the acetate compared to the chloride counter ion in the resulting pyrylium salt. The reactivity of the FS 101 amorphous carbon (3.7·10 15 molecule/cm2) and the hexane flame soot (between 1.9·10 15 and 2.7·10 15 molecule/cm2) towards O3 was very high, indicating the presence of a huge amount of oxidizable or reduced groups on the surface of these samples. Besides the quantification of surface functional groups, the kinetics of reactions between particles and probe gases has also been studied. The uptake coefficient γ0 was roughly correlated with the amount of probe gas taken up by the samples. Indeed, the presence of a high density of functional groups led to fast uptake of the probe gas. These different findings indicate that the particle surface appeared multi-functional, with the simultaneous presence of antagonistic functional groups which do not undergo internal chemical reactions, such as acid-base neutralization. Results also point to important differences in the surface reactivity of the samples, depending on the combustion conditions. The relative distribution of the surface functional groups may be a useful indicator for the state of oxidation and the reactivity of the particle surface.

Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy.

BACKGROUND: Leprosy is characterized by a spectrum of clinical manifestations that depend on the type of immune response against the pathogen. Patients may undergo immunological changes known as "reactional states" (reversal reaction and erythema nodosum leprosum) that result in major clinical deterioration. The goal of the present study was to assess the effect of Toll-like receptor 2 (TLR2) polymorphisms on susceptibility to and clinical presentation of leprosy. METHODS: Three polymorphisms in TLR2 (597C--&gt;T, 1350T--&gt;C, and a microsatellite marker) were analyzed in 431 Ethiopian patients with leprosy and 187 control subjects. The polymorphism-associated risk of developing leprosy, lepromatous (vs. tuberculoid) leprosy, and leprosy reactions was assessed by multivariate logistic regression models. RESULTS: The microsatellite and the 597C--&gt;T polymorphisms both influenced susceptibility to reversal reaction. Although the 597T allele had a protective effect (odds ratio [OR], 0.34 [95% confidence interval {CI}, 0.17-0.68]; P= .002 under the dominant model), homozygosity for the 280-bp allelic length of the microsatellite strongly increased the risk of reversal reaction (OR, 5.83 [95% CI, 1.98-17.15]; P= .001 under the recessive model). These associations were consistent among 3 different ethnic groups. CONCLUSIONS: These data suggest a significant role for TLR-2 in the occurrence of leprosy reversal reaction and provide new insights into the immunogenetics of the disease.

Reverse transcription quantitative real-time polymerase chain reaction reference genes in the spared nerve injury model of neuropathic pain: validation and literature search.

BACKGROUND: The reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used, highly sensitive laboratory technique to rapidly and easily detect, identify and quantify gene expression. Reliable RT-qPCR data necessitates accurate normalization with validated control genes (reference genes) whose expression is constant in all studied conditions. This stability has to be demonstrated.We performed a literature search for studies using quantitative or semi-quantitative PCR in the rat spared nerve injury (SNI) model of neuropathic pain to verify whether any reference genes had previously been validated. We then analyzed the stability over time of 7 commonly used reference genes in the nervous system - specifically in the spinal cord dorsal horn and the dorsal root ganglion (DRG). These were: Actin beta (Actb), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal proteins 18S (18S), L13a (RPL13a) and L29 (RPL29), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS). We compared the candidate genes and established a stability ranking using the geNorm algorithm. Finally, we assessed the number of reference genes necessary for accurate normalization in this neuropathic pain model. RESULTS: We found GAPDH, HMBS, Actb, HPRT1 and 18S cited as reference genes in literature on studies using the SNI model. Only HPRT1 and 18S had been once previously demonstrated as stable in RT-qPCR arrays. All the genes tested in this study, using the geNorm algorithm, presented gene stability values (M-value) acceptable enough for them to qualify as potential reference genes in both DRG and spinal cord. Using the coefficient of variation, 18S failed the 50% cut-off with a value of 61% in the DRG. The two most stable genes in the dorsal horn were RPL29 and RPL13a; in the DRG they were HPRT1 and Actb. Using a 0.15 cut-off for pairwise variations we found that any pair of stable reference gene was sufficient for the normalization process. CONCLUSIONS: In the rat SNI model, we validated and ranked Actb, RPL29, RPL13a, HMBS, GAPDH, HPRT1 and 18S as good reference genes in the spinal cord. In the DRG, 18S did not fulfill stability criteria. The combination of any two stable reference genes was sufficient to provide an accurate normalization.