BackgroundCostimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer.MethodsB7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells.ResultsB7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018).ConclusionWe demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.

B7-H3 is one of the most recently identified members of the B7/CD28 superfamily of costimulatory molecules serving as an accessory modulator of T-cell response. Recently, B7-H3 expression has been reported in several human cancers indicating an additional function of B7-H3 as a regulator of antitumor immunity. However, its precise physiologic role is still elusive, because both stimulatory and inhibitory capacities have been demonstrated. This paper summarizes the available data on B7-H3 in the regulation of T-cell response focusing on its potential role in antitumor immunity.

Background and Purpose-Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods-Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δ t) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results-Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δ t : r=0.43, P=0.016/ε: r=0.45, P=0.01) and inversely with red blood cells counts (Δ t : r=−0.46, P=0.01/ε: r=−0.49, P=0.006). In the first cohort, Δ t was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi (P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δ t : median [ interquartile range]=12.53 [8.70-17.90]; ε: median [interquartile range]=0.054 [0.036-0.082]) and noncardioembolic thrombi (Δ t : median [interquartile range]=3.2 [2.17-6.44], P<0.001; ε: median [interquartile range]=0.020 [0.011-0.027], P<0.001) and were associated with pathogenesis (Δ t : β=0.45, P=0.016/ε: β=83.6, P=0.013) in a binary logistic regression model. Conclusions-Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.

BackgroundFibrofatty degeneration of myocardium in ARVC is associated with wall motion abnormalities. The aim of this study was to examine whether Cardiovascular Magnetic Resonance (CMR) based strain analysis using feature tracking (FT) can serve as a quantifiable measure to confirm global and regional ventricular dysfunction in ARVC patients and support the early detection of ARVC.MethodsWe enrolled 20 patients with ARVC, 30 with borderline ARVC and 22 subjects with a positive family history but no clinical signs of a manifest ARVC. 10 healthy volunteers (HV) served as controls. 15 ARVC patients received genotyping for Plakophilin-2 mutation (PKP-2), of which 7 were found to be positive. Cine MR datasets of all subjects were assessed for myocardial strain using FT (TomTec Diogenes Software). Global strain and strain rate in radial, circumferential and longitudinal mode were assessed for the right and left ventricle. In addition strain analysis at a segmental level was performed for the right ventricular free wall.ResultsRV global longitudinal strain rates in ARVC (−0.68 ± 0.36 sec−1) and borderline ARVC (−0.85 ± 0.36 sec−1) were significantly reduced in comparison with HV (−1.38 ± 0.52 sec−1, p ≤ 0.05). Furthermore, in ARVC patients RV global circumferential strain and strain rates at the basal level were significantly reduced compared with HV (strain: −5.1 ± 2.7 vs. -9.2 ± 3.6%; strain rate: −0.31 ± 0.13 sec−1 vs. -0.61 ± 0.21 sec−1). Even for patients with ARVC or borderline ARVC and normal RV ejection fraction (n=30) global longitudinal strain rate proved to be significantly reduced compared with HV (−0.9 ± 0.3 vs. -1.4 ± 0.5 sec−1; p < 0.005). In ARVC patients with PKP-2 mutation there was a clear trend towards a more pronounced impairment in RV global longitudinal strain rate. On ROC analysis RV global longitudinal strain rate and circumferential strain rate at the basal level proved to be the best discriminators between ARVC patients and HV (AUC: 0.9 and 0.92, respectively).ConclusionCMR based strain analysis using FT is an objective and useful measure for quantification of wall motion abnormalities in ARVC. It allows differentiation between manifest or borderline ARVC and HV, even if ejection fraction is still normal.

Summary This feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow using chemical shift encoding–based water-fat MRI. Acquired texture features like contrast and dissimilarity allowed for differentiation of pre- and postmenopausal women and may serve as imaging biomarkers in the future. Introduction While the vertebral bone marrow fat using chemical shift encoding water-fat magnetic resonance imaging (MRI) has been extensively studied, its spatial heterogeneity has not been analyzed yet. Therefore, this feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow by using texture analysis in proton density fat fraction (PDFF) maps. Methods Forty-one healthy pre- and postmenopausal women were recruited for this study (premenopausal ( n = 15) 30 ± 7 years, postmenopausal ( n = 26) 65 ± 7 years). An eight-echo 3D spoiled gradient echo sequence was used for chemical shift encoding–based water-fat separation at the lumbar spine. Vertebral bodies L1 to L5 were manually segmented. Mean PDFF values and texture features were extracted at each vertebral level, namely variance, skewness, and kurtosis, using statistical moments and second-order features (energy, contrast, correlation, homogeneity, dissimilarity, entropy, variance, and sum average). Parameters were compared between pre- and postmenopausal women and vertebral levels. Results PDFF was significantly higher in post- than in premenopausal women (49.37 ± 8.14% versus 27.76 ± 7.30%, p < 0.05). Furthermore, PDFF increased from L1 to L5 (L1 37.93 ± 12.85%, L2 38.81 ± 12.77%, L3 40.23 ± 12.72%, L4 42.80 ± 13.27%, L5 45.21 ± 14.55%, p < 0.05). Bone marrow heterogeneity based on texture analysis was significantly ( p < 0.05) increased in postmenopausal women. Contrast and dissimilarity performed best in differentiating pre- and postmenopausal women (AUC = 0.97 and 0.96, respectively), not significantly different compared with PDFF (AUC = 0.97). Conclusion Conclusively, an increased bone marrow heterogeneity could be observed in postmenopausal women. In the future, texture parameters might provide additional information to detect and monitor vertebral bone marrow alterations due to aging or hormonal changes beyond conventional anatomic imaging.

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Abnormal alterations in cerebrospinal fluid (CSF) flow are thought to play an important role in pathophysiology of various craniospinal disorders such as hydrocephalus and Chiari malformation. Three directional phase contrast MRI (4D Flow) has been proposed as one method for quantification of the CSF dynamics in healthy and disease states, but prior to further implementation of this technique, its accuracy in measuring CSF velocity magnitude and distribution must be evaluated. In this study, an MR-compatible experimental platform was developed based on an anatomically detailed 3D printed model of the cervical subarachnoid space and subject specific flow boundary conditions. Accuracy of 4D Flow measurements was assessed by comparison of CSF velocities obtained within the in vitro model with the numerically predicted velocities calculated from a spatially averaged computational fluid dynamics (CFD) model based on the same geometry and flow boundary conditions. Good agreement was observed between CFD and 4D Flow in terms of spatial distribution and peak magnitude of through-plane velocities with an average difference of 7.5% and 10.6% for peak systolic and diastolic velocities, respectively. Regression analysis showed lower accuracy of 4D Flow measurement at the timeframes corresponding to low CSF flow rate and poor correlation between CFD and 4D Flow in-plane velocities.