Microbubble-mediated delivery of human adenoviruses does not elicit innate and adaptive immunity response in an immunocompetent mouse model of prostate cancer.

BACKGROUND: Gene transfer to malignant sites using human adenoviruses (hAds) has been limited because of their immunogenic nature and host specificity. Murine cells often lack some of the receptors needed for hAds attachment, thus murine cells are generally non-permissive for human adenoviral infection and replication, which limits translational studies. METHODS: We have developed a gene transfer method that uses a combination of lipid-encapsulated perfluorocarbon microbubbles and ultrasound to protect and deliver hAds to a target tissue, bypassing the requirement of specific receptors. RESULTS: In an in vitro model, we showed that murine TRAMP-C2 and human DU145 prostate cancer cells display a comparable expression pattern of receptors involved in hAds adhesion and internalization. We also demonstrated that murine and human cells showed a dose-dependent increase in the percentage of cells transduced by hAd-GFP (green fluorescent protein) after 24 h and that GFP transgene was efficiently expressed at 48 and 72 h post-transduction. To assess if our image-guided delivery system could effectively protect the hAds from the immune system in vivo, we injected healthy immunocompetent mice (C57BL/6) or mice bearing a syngeneic prostate tumor (TRAMP-C2) with hAd-GFP/MB complexes. Notably, we did not observe activation of innate (TNF-α and IL-6 cytokines), or adaptive immune response (neutralizing antibodies, INF-γ+ CD8+ T cells). CONCLUSIONS: This study brings us a step closer to demonstrating the feasibility of murine cancer models to investigate the clinical translation of image guided site-specific adenoviral gene therapy mediated by ultrasound-targeted microbubble destruction.

Computed Tomography and Dual-Energy X-Ray Asorptiometry body composition parameter harmonisation to universalise adipose tissue measurements in a population-based cross-sectional study.

To harmonise computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) body composition measurements allowing easy conversion in longitudinal assessments and across cohorts to assess cardiometabolic risk and disease. Retrospective cross-sectional observational study from 1996 to 2008 included participants in the Pennington Center Longitudinal Study (PCLS) (N = 1967; 571 African American/1396 White). Anthropometrics, whole-body DXA and abdominal CT images were obtained. Multi-layer segmentation techniques (Analyze; Rochester, MN) quantified visceral adipose tissue (VAT). Clinical biomarkers were obtained from routine blood samples. Linear models were used to predict CT-VAT from DXA-VAT and examine the effects of traditional biomarkers on cross-sectional-VAT. Predicted CT-VAT was highly associated with measured CT-VAT using ordinary least square linear regression analysis and random forest models (R2 = 0.84; 0.94, respectively, p < .0001). Model stratification effects showed low variability between races and sexes. Overall, associations between measured CT-VAT and DXA-predicted CT-VAT were good (R2 > 0.7) or excellent (R2 > 0.8) and improved for all stratification groups except African American men using random forest models. The clinical effects on measured CT-VAT and DXA-VAT showed no significant clinical difference in the measured adipose tissue areas (mean difference = 0.22 cm2). Random forest modelling seamlessly predicts CT-VAT from measured DXA-VAT to a degree of accuracy that falls within the bounds of universally accepted standard error.

A deceptive mass on neonatal ultrasound and a fetal brain MRI-confirmed complex dural arteriovenous fistula postnatally: illustrative case.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) are direct, aberrant connections between dural arteries and cerebral veins. In neonates, delayed diagnosis results in grim outcomes. Treatment involves endovascular management because of its success and tolerability. Here, the authors present a case of a complex dAVF initially recognized with an in utero neurosonogram and fetal magnetic resonance imaging (MRI). OBSERVATIONS: A 21-week fetal ultrasound of a nonspecific brain mass was confirmed with fetal MRI as a 2.7-cm T1-hyperintense posterior fossa mass. Although a large flow void in the left middle cranial fossa was present, postnatal computed tomography angiography ultimately revealed a high-flow dAVF communicating with the left transverse sinus. In the early postnatal period, the patient developed hydrocephalus. After successful partial embolization, 6-week postangiogram brain MRI indicated disease progression with the development of a venous varix causing brainstem compression. Repeat embolization resulted in complete cessation of early venous drainage. LESSONS: Neonatal dAVFs are exceedingly rare and result in futile outcomes; however, detection in utero is possible. Although definitive therapy must be performed postnatally, constant monitoring and early delivery can prevent complications. Attention to fetal ultrasound is essential, and knowledge of fetal MRI in the detection of these complex lesions can significantly improve outcomes.

Planning C2 pedicle screw placement with multiplanar reformatted cervical spine computed tomography.

OBJECT: Careful preoperative planning with thin-slice computed tomography (CT) scan is useful for hardware placement at C2. Prior studies have shown considerable variability in the proportion of C2 vertebrae considered safe for pedicle screw placement, depending on the imaging technique used. Our work sought to more carefully define that proportion using a refined imaging technique on a large number of submillimeter CT scans. MATERIALS AND METHODS: We reviewed 150 submillimeter cervical spine studies randomly selected from CT scans performed at a Level 1 trauma center. OsiriX™ image analysis software was used to propagate a 5-mm cylinder through the plane of the pedicle on paracoronal reformatted CT scans. Hounsfield unit attenuation was used to determine whether the cylinder violated the pedicle. Binomial data were generated to determine the proportion of pedicles that would allow safe screw placement. RESULTS: We analyzed 300 pedicles in 150 patients. Using a standard C2 pedicle starting point, 32% of pedicles were breached by the 5-mm diameter cylinder. When screw trajectory was adjusted by moving the cylinder to fit the pedicle isthmus, establishing an optimized starting point, only 14% of pedicles were breached. Average pedicle length was 27.3 mm for screws that would have crossed the isthmus versus 13.2 mm for screws that would have stopped short due to potential breach. CONCLUSIONS: Findings of the current work suggest that preoperative imaging analysis or navigation can be useful adjuncts when anatomical variants are present.