Hyperpolarized helium-3 magnetic resonance lung imaging of non-sedated infants and young children: a proof-of-concept study.

PURPOSE: To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. MATERIALS AND METHODS: HHe ventilation MRI was performed on seven children ≤4years old. Contiguous 2D-spiral helium-3 images were acquired sequentially with a scan time of ≤0.2s/slice. RESULTS: Motion-artifact-free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained. Gas was homogeneously distributed in healthy individuals; focal ventilation defects were found in patients with respiratory diseases. CONCLUSION: HHe ventilation MRI can aid assessment of pediatric lung disease even at a young age.

Intrahepatic and Peripheral CXCL10 Expression in Hepatitis C Virus-Infected Patients Treated With Telaprevir, Pegylated Interferon, and Ribavirin.

UNLABELLED: We assessed peripheral and liver CXCL10 levels in 15 patients treated with telaprevir/pegylated interferon/ribavirin. Induction of peripheral CXCL10 messenger RNA (mRNA) peaked (mean fold-induction [±SD], 3.1 ± 1.9) between treatment hour 6 and day 2, while induction of intrahepatic CXCL10 mRNA peaked (mean fold-induction [±SD], 1.3 ± 0.54) at hour 10 or day 4. Peripheral CXCL10 levels were higher at treatment hour 10 (P = .032) and day 2 (P = .009) in patients with undetectable virus 2 weeks after treatment initiation. Treatment hour 10 (P = .023) and peak (P = .034) intrahepatic CXCL10 levels were also higher in these patients. CXCL10 did not distinguish treatment responders from nonresponders. In conclusion, CXCL10 identified very rapid virological response in patients treated with a direct-acting antiviral. CLINICAL TRIALS REGISTRATION: NCT00892697.

Telaprevir-based treatment effects on hepatitis C virus in liver and blood.

UNLABELLED: Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug-resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated-interferon alpha/ribavirin. Hepatic fine needle aspiration was performed before treatment and at hour 10, days 4 and 15, and week 8 after initiation of antiviral therapy. We measured viral kinetics, resistance patterns, TVR concentrations, and host transcription profiles. All patients completed all protocol-defined procedures that were generally well tolerated. First-phase HCV decline (baseline/treatment day 4) was significantly slower in liver than in plasma (slope plasma: -0.29; liver, -0.009; P < 0.001), whereas second-phase decline (posttreatment days 4-15) did not differ between the two body compartments (-0.11 and -0.15, respectively; P = 0.1). TVR-resistant variants were detected in plasma, but not in liver (where only wild-type virus was detected). Based upon nonstructural protein 3 sequence analysis, no compartmentalization of viral populations was observed between plasma and liver compartments. Gene expression profiling revealed strong tissue-specific expression signatures. Human intrahepatic TVR concentration, measured for the first time, was lower, compared to plasma, on a gram per milliliter basis. We found moderate heterogeneity between HCV RNA levels from different intrahepatic sites, indicating differences in hepatic microenvironments. CONCLUSION: These data support an integrated model for HCV replication wherein the host hepatic milieu and innate immunity control the level of viral replication, and the early antiviral response observed in the plasma is predominantly driven by inhibition of hepatic high-level HCV replication sites.