. Diagnostic accuracy and interobserver variability of pulsed arterial spin labeling for glioma grading. Acta Radiol 2008;49:450Á457.Background: Although pulsed arterial spin labeling (PASL) enables the reliable qualitative grading of brain tumors, its use in quantification for glioma grading may be hampered by the limited interobserver variability associated with low spatial resolution. Purpose: To assess the interobserver variability and diagnostic accuracy of the relative tumor perfusion signal intensity (rTPS) calculated using PASL in glioma grading. Material and Methods: Fifty-eight patients with 61 cerebral astrocytomas underwent conventional MR imaging and PASL. Receiver operating characteristic analyses were used to determine the optimum thresholds for tumor grading. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying highgrade gliomas were also calculated. Cohen's k statistic was used to determine the levels of interobserver variability in the quantitative analysis of PASL. Results: The sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 77.1, 73.1, 79.4, and 70.4%, respectively. A threshold value of 1.28 for rTPS provided a sensitivity, specificity, PPV, and NPV of 82.9, 96.2, 96.7, and 80.6%, respectively. There was a statistically significant difference in the rTPS between low-and high-grade astrocytomas (1.14 vs. 1.47, P B0.05). In the interobserver variability analysis, substantial agreement was obtained for the quantitative rTPS measurement from PASL (k 00.72). Conclusion: Quantitative perfusion measurement with PASL can improve the diagnostic accuracy of preoperative glioma grading, as compared to the application of conventional imaging alone. However, the interobserver variability for quantification is substantial.

Inhibitor development is the most significant complication in the therapy of haemophilia A (HA) patients. In spite of many studies, not much is known regarding the mechanism underlying inhibitor development. To understand the mechanism, we analysed profiles of differentially expressed genes (DEGs) between inhibitor and non-inhibitor HA via a microarray technique. Twenty unrelated Korean HAs were studied: 11 were non-inhibitor and nine were HA with inhibitor (≥5 BU mL(-1)). Microarray analysis was conducted using a Human Ref-8 expression Beadchip system (Illumina) and the data were analysed using Beadstudio software. We identified 545 DEGs in inhibitor HA as compared with the non-inhibitor patients; 384 genes were up-regulated and 161 genes were down-regulated. Among them, 75 genes whose expressions were altered by at least two-fold (>+2 or <-2) were selected and classified via the PANTHER classification method. The expressions of signal transduction and immunity-related genes differed significantly in the two groups. For validation of the DEGs, semi-quantitative RT-PCR (semi-qRT-PCR) was conducted with the six selected DEGs. The results corresponded to the microarray data, with the exception of one gene. We also examined the expression of the genes associated with the antigen presentation process via real-time PCR. The average levels of IL10, CTLA4 and TNFα slightly reduced, whereas that of IFNγ increased in the inhibitor HA group. We are currently unable to explain whether this phenomenon is a function of the inhibitor-inducing factor or is an epiphenomenon of antibody production. Nevertheless, our results provide a possible explanation for inhibitor development.