High resolution 3T fMRI in anesthetized monkeys

Although there are numerous 3 T MRI research devices all over the world, only a few functional studies at 3 T have been done in anesthetized monkeys. In the past, anesthetized preparations were reported to be misleading when exploring cortical brain regions outside the primary sensory areas. Nonetheless, a great improvement has been achieved in the limited effect of anesthetic agents on the reactivity of the brain.Here, we re-address the feasibility and potential applications of the brain oxygen level dependent (BOLD) fMRI signal in Macaca mulatta monkeys that have been lightly anesthetized with sevoflurane and curarized. The monkeys were studied with commercially available coils and sequences using a 3 T clinical magnet. We obtained sagittal T1 scout images, gray matter double inversion recovery, standard gradient echo sequences and gradient echo functional imaging sequences. Given that fMRI signals are most readily identified in the cerebral cortices, we optimized Echo Planar Imaging sequences to reproduce significant changes in the BOLD signal subsequent to a visual stimulation paradigm.Our results provide a satisfactory signal to noise ratio with a limited standard deviation range, when compared with studies on alert macaques.We suggest that the 3 T magnet remains a valuable tool to analyze neural pathways in the macaque brain under light anesthesia and report the use of spatially resolved fMRI in higher visual areas of anesthetized monkeys. This methodology avoids the need for time-consuming training of awake monkeys, is stable over many hours, provides reproducible data and could be applied successfully to future functional studies.     

Comparing the Detectability of Hepatocellular Carcinoma by C-Arm Dual-Phase Cone-Beam Computed Tomography During Hepatic Arteriography With Conventional Contrast-Enhanced Magnetic Resonance Imaging

Purpose  

To evaluate the sensitivity of dual-phase cone-beam computed tomography during hepatic arteriography (CBCTHA) for the detection of hepatocellular carcinoma (HCC) by comparing it with the diagnostic imaging “gold standard”: contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver.     

Comparison of the effects of erythropoietin and its carbamylated derivative on behaviour and hippocampal neurogenesis in mice

Erythropoietin (EPO), a well known haematopoietic growth factor, possesses neuroprotective and neurotrophic effects which have been recently reported to improve cognition and to modulate emotional processing. We investigated the effects of EPO and of its non-erythropoietic carbamylated derivative (CEPO) on memory- and emotion-related behaviour in the adult mouse. Locomotor activity, memory performances (place and object recognition tasks), anxiety- (light/dark transition test) and despair-like behaviours (tail suspension test) were assessed over 6 weeks of repeated EPO or CEPO administration (40 μg/kg, twice a week). Given the potential involvement of hippocampal neurogenesis in memory, we also assessed the effects of EPO and CEPO on neurogenesis in the dentate gyrus. Both treatments improved spatial and non-spatial recognition memory and increased the number of NeuN/BrdU double-labeled cells in the dentate gyrus. These effects seem to be, at least partly, independent from an haematopoietic action since administration of CEPO leads to the similar results. Moreover, CEPO decreased, albeit modestly, despair-related behaviour and tended to decrease anxiety-like behaviour. These results suggest that CEPO is as an attractive molecule for the treatment of neuropsychiatric diseases associating memory and/or emotional disorders.     

Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients.The association between the development of metastasis and the risk of thrombotic complications has been documented since 1865. Armand Trousseau was the first to establish a direct correlation between thrombophlebitis and the development of cancer (Trousseau, 1865). A rather common complication and one of the leading causes of death in patients with cancer is the risk of developing thromboembolic diseases (Kakkar and Williamson, 1999; Stein et al., 2006; Schiavetti et al., 2008). The incidence of thrombosis is high in adenocarcinomas such as ovarian, prostate, lung, and gastrointestinal carcinomas (Blom et al., 2006b), and it is particularly high (up to 57%) in patients suffering from pancreatic cancer (Sack et al., 1977; Blom et al., 2006a). In the latter case, thromboembolic diseases are the second most common cause of mortality, accounting for 44% of total deaths after cancer progression (Neoptolemos et al., 2001). The recurrence of thrombotic complications may also be the first manifestation of underlying malignant disease (Prandoni et al., 1992).The pathogenesis of the thrombotic state in cancer is associated with the generation of a local and systemic hypercoagulable/thrombotic state that confers a growth advantage to tumor cells. It is now known that activation of the coagulation cascade and aggregation of blood platelets around cancer cells protects the cells from the different degradative pathways present in the blood, and also facilitates dissemination of cancer cells to various sites of metastasis (Gasic et al., 1976; Sierko and Wojtukiewicz, 2007). This supports a model in which the presence of tissue factor (TF), generation of thrombin, and activation of platelets favor the aggressive biology of cancer. Nevertheless, the cause of this association remains unclear.Different reports suggest a potential role for circulating microparticles (MPs) in the establishment of a thrombotic state in cancer (Kim et al., 2003; Del Conde et al., 2007; Tilley et al., 2008). MPs are defined as cell-derived membrane fragments and range in size from 0.1 to 1 µm in diameter. They are characterized by their presence at the surface of negative phospholipid moieties that are essential for initiation of blood coagulation (Ghosh et al., 2008); they also bear at least one of the antigenic markers distinctive of the parent cell (Abid Hussein et al., 2003). Aggregated platelets, leukocytes, erythrocytes, and endothelial lineages constitute the most important sources of circulating MPs under many pathophysiological situations, including thrombosis, inflammation, and angiogenesis (Müller et al., 2003). Recent clinical studies have shown that the concentration of circulating TF-bearing MPs is significantly greater in patients with cancer (Tilley et al., 2008), including patients with pancreatic cancer (Del Conde et al., 2007; Hron et al., 2007; Tesselaar et al., 2007), suggesting that these MPs may be responsible for the thrombotic state associated with cancers. Meanwhile, the cellular origins of such MPs have not been determined (Hron et al., 2007; Zwicker et al., 2007; Langer et al., 2008) and may include platelets (Hron et al., 2007; Tesselaar et al., 2007), cancer cells (Dvorak et al., 1981), or monocytes (Falati et al., 2003; Myers et al., 2003; Vandendries et al., 2007). At their surface, platelet-derived MPs express activated integrins (e.g., α_IIbβ₃ or α_vβ₃) and receptors (i.e., GPVI and GPIb-IX-V) known to be involved in thrombus formation. Monocyte-derived MPs that have been isolated, labeled, and infused into a recipient mouse accumulate at the site of a laser-induced injury by binding to P-selectin expressed on activated platelets through P-selectin glycoprotein ligand 1 (PSGL-1; Falati et al., 2003; Vandendries et al., 2007). To date, no study has determined the role of cancer cell–derived MPs in thrombus formation in vivo.In the present study, we hypothesize that cancer cell–derived MPs bearing PSGL-1 are involved in the development of a thrombotic state. We demonstrate that pancreatic cancer cells are able to produce MPs in vitro that express active TF and PSGL-1. We show that cancer cell–derived MPs circulate in the bloodstream and accumulate at the site of injury in a P-selectin–dependent manner in vivo. Finally, we observe that cancer cell–derived MPs, but not their parental cells, accelerate thrombus formation in a mouse model of cancer.     

Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus

Background

In patients with chronic hepatitis C virus, liver biopsy is the gold standard for assessing liver disease stage; nevertheless, it is prone to complications, some of them serious. Non-invasive methods have been proposed as surrogate markers for liver fibrosis. It was shown that serum hyaluronic acid (HA) level increases with the development for liver fibrosis. The aim of this study was to evaluate the diagnostic value of HA as well as to determine the HA level cut-off for predicting the presence or absence of fibrosis, severe fibrosis, and cirrhosis.

Results

405 patients with chronic hepatitis C were prospectively included with biomarker measurement and liver biopsy done the same day: 151 in the training set (only biopsy lengths of 25 mm or more) and 254 in the validation set. For the discrimination of significant fibrosis, severe fibrosis, and cirrhosis in the training set, the areas under curve (AUCs) were 0.75 ± 0.03, 0.82 ± 0.02, and 0.89 ± 0.03, respectively. Absence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 16, 25, and 50 μg/l, respectively (with negative predictive values of 82%, 89%, and 100%, in the same order). Presence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 121, 160, and 237 μg/l, respectively (with positive predictive values of 94%, 100%, and 57%, in the same order).

Conclusion

In the validation set, HA was accurate in predicting significant fibrosis, severe fibrosis, and cirrhosis with AUCs of 0.73, 0.77, and 0.97, respectively. Moreover, accurate HA level cut-offs were defined for predicting significant fibrosis, severe fibrosis, and cirrhosis. Thus, the study supports that HA level may be clinically useful as a non-invasive marker for liver fibrosis and/or cirrhosis.     

Outcomes of Transcatheter Arterial Embolization with a Modified N-Butyl Cyanoacrylate Glue for Spontaneous Iliopsoas and Rectus Sheath Hematomas in Anticoagulated Patients

Purpose

To assess the efficacy and safety of n-butyl cyanoacrylate methacryloxy sulfolane (NBCA-MS) transcatheter arterial embolization for anticoagulation-related soft-tissue bleeding and to evaluate predictive factors of clinical success and 30-day mortality.

MRI diagnosis and follow-up of hepatic infarction in a patient with antiphospholipid syndrome in early pregnancy

Hepatic infarction is rare in hemolysis, elevated liver enzymes, and low platelets syndrome. We described a case of a 24-year-old woman who was admitted at week 17 of pregnancy with an antiphospholipid syndrome. Magnetic resonance imaging was the imaging modality of choice for diagnosing hepatic infarction, guiding treatment, ensuring the early detection of bleeding, and monitoring liver recovery.     

Serum Arginase,a Biomarker of Treatment Efficacy in Human African Trypanosomiasis

Arginase serum levels were increased in human African trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes l-arginine to l-ornithine, which is essential for parasite growth. Moreover, l-arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy.