Can T1w/T2w ratio be used as a myelin‐specific measure in subcortical structures? Comparisons between FSE‐based T1w/T2w ratios,GRASE‐based T1w/T2w ratios and multi‐echo GRASE‐based myelin water fractions

Given the growing popularity of T₁‐weighted/T₂‐weighted (T₁w/T₂w) ratio measurements, the objective of the current study was to evaluate the concordance between T₁w/T₂w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T₂w image acquisition, and to compare the resulting T₁w/T₂w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole‐brain T₁w magnetization prepared rapid acquisition gradient echo (MPRAGE), T₂w FSE and three‐dimensional multi‐echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high‐dimensional, non‐linear warping, region of interest (ROI) analyses were performed to compare T₁w/T₂w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS ‘Eve’ atlas. Although the GRASE sequence systematically underestimated T₁w/T₂w values compared to the FSE sequence (revealed by Bland–Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r² = 0.62 for all ROIs, r² = 0.62 for WM structures and r² = 0.73 for SGM structures). However, correlations between either FSE‐based or GRASE‐based T₁w/T₂w ratios and MWFs were extremely low in WM structures (FSE‐based, r² = 0.000020; GRASE‐based, r² = 0.0014), low across all ROIs (FSE‐based, r² = 0.053; GRASE‐based, r² = 0.029) and moderate in SGM structures (FSE‐based, r² = 0.20; GRASE‐based, r² = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE‐based and GRASE‐based T₁w/T₂w ratios, and low correlations between T₁w/T₂w ratios and MWFs. This suggests that the two T₁w/T₂w ratio approaches measure similar facets of subcortical tissue microstructure, whereas T₁w/T₂w ratios and MWFs appear to be sensitized to different microstructural properties. On this basis, we conclude that multi‐echo GRASE sequences can be used in future studies to efficiently elucidate both general (T₁w/T₂w ratio) and myelin‐specific (MWF) tissue characteristics.     

Análisis del polimorfismo rs20541 (R130Q) del gen de la IL-13 en pacientes con enfermedades inflamatorias crónicas asociadas al envejecimiento

ObjectiveTo investigate whether there is association between the rs20541 (R130Q) polymorphism in the IL-13 gene with disease susceptibility and clinical subsets in patients with elderly-associated inflammatory chronic diseases.Material and methods78 patients with giant cell arteritis (GCA), 174 with polymyalgia rheumatica (PMR), 90 elderly-onset rheumatoid arthritis (EORA), and 465 healthy controls from the same geographic area were studied. The rs20541 (R130Q) polymorphism in the IL-13 gene was evaluated by PCR-RFLP. Circulating levels of IL-13 were measured by ELISA.ResultsA higher frequency of the AA genotype [2.349 (0.994-5.554)], as well as the allele A [1.589 (1.085-2.328] and the A carriers [1.656 (1.021-2.686)] (p < 0.05) was observed in the GCA patients. No significant differences were observed in the PMR and EORA patients as compared with the healthy controls. Neither difference was observed among the different disease groups studied. In GCA patients, differences in the genotype were associated with a worse prognosis. In PMR patients, the AA genotype was associated with higher levels of serum IL-13 than the GA one. However, such an association was not detected for controls and the other disease groups.ConclusionsGCA is more frequent in carriers of the rs20541 (R130Q) polymorphism in the IL-13 gene. The utility of this polymorphism to predict the GCA prognosis must be confirmed in studies with a higher number of patients.     

Blood-based biomarkers for monitoring antiangiogenic therapy in non-small cell lung cancer

Tumor angiogenesis pathways have been identified as important therapeutic targets in non-small cell lung cancer. However, no biomarkers have been described as predictors of response to antiangiogenic therapy in these patients. In this study, plasma levels of VEGF, bFGF, E-selectin, and S-ICAM and gene expression profiles of peripheral blood mononuclear cells from non-small cell lung cancer patients treated with chemotherapy plus bevacizumab were analyzed before and after treatment. Values were correlated with clinicopathological characteristics and treatment response. Plasma factor levels were measured using commercially available ELISA kits. The TaqMan^® human angiogenesis array was used to investigate the effect of treatment on gene expression profiles. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis was performed for differentially expressed genes using WEB-based GEne SeT AnaLysis Toolkit. Our results suggest a benefit for patients with increased plasma levels of VEGF, E-selectin, and S-ICAM in the course of bevacizumab treatment. Also, we identified differentially expressed genes between paired blood samples from patients before and after treatment, and significantly perturbed pathways were predicted. These changes in gene expression and levels of plasma factors could be used to assess the effectiveness of antiangiogenic therapy, in addition to standard clinical and radiological evaluations.