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.

Prospective validation of a rapid CT-based bone mineral density screening method using colored spinal images.

PURPOSE: To prospectively validate a method to accurately and rapidly differentiate normal from abnormal spinal bone mineral density (BMD) using colored abdominal CT images. METHODS: For this prospective observational study, 196 asymptomatic women ≥ 50 years of age presenting for screening mammograms underwent routine nonenhanced CT imaging of the abdomen. The CT images were processed with software designed to generate sagittal colored images with green vertebral trabecular bone indicating normal BMD and red indicating abnormal BMD (low BMD or osteoporosis). Four radiologists evaluated L1/L2 BMD on sagittal images using visual assessment of grayscale images, quantitative measurements of mean vertebral attenuation, and visual assessment of colored images. Mean BMD values at L1/L2 using quantitative CT with a phantom served as the reference standard. The average accuracy and time of interpretation were calculated. Inter-observer agreement was assessed using intraclass correlation coefficient (ICC). RESULTS: Mean attenuation at L1/L2 was highly correlated with mean BMD (r = 0.96/0.91, p < 0.001 for both). The average accuracy and mean time to assess BMD among four readers for differentiating normal from abnormal BMD was 66% and 6.0 s using visual assessment of grayscale images, 88% and 15.2 s using quantitative measurements of mean vertebral attenuation, and 92% and 2.1 s using visual assessment of colored images (p < 0.001 and p < 0.001, respectively). Inter-observer agreement was poor using visual assessment of grayscale images (ICC:0.31), good using quantitative measurements of mean vertebral attenuation (ICC:0.73), and excellent using visual assessment of colored images (ICC:0.90). CONCLUSION: Detection of abnormal BMD using colored abdominal CT images was highly accurate, rapid, and had excellent inter-observer agreement.

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.

Opportunistic bone density screening for the abdominal radiologist using colored CT images: a pilot retrospective study.

PURPOSE: The purpose of the study was to develop an accurate and reproducible method for detecting low spinal bone density on abdominal CT images. METHODS: For this IRB-approved HIPAA-compliant single-center retrospective study, nonenhanced CT images of the lower abdomen were obtained in 631 African-American participants. Mean attenuation of L3/L4 was associated with quantitative CT bone density (QCT) in a randomly selected training cohort (N = 511), and receiver operating characteristics analysis was used to identify the optimal mean attenuation threshold for differentiating normal from low bone density. Custom image processing software was used to generate grayscale and colored CT images of the midline spine, with green for normal and red for low bone density. Five radiologists independently assessed bone density at L3/L4 in a validation cohort (N = 120) using various methods: QCT, visual assessment of sagittal grayscale images (Grayscale), quantitative measurement of mean attenuation on a midline sagittal image (Attenuation), and visual assessment of a midline sagittal colored image (Color). Accuracy was calculated using the average QCT bone density as a reference standard. Inter-observer agreement was assessed using intraclass correlation coefficient (ICC). RESULTS: The optimal mean attenuation threshold for differentiating normal from low bone density at L3/L4 was 145 Hounsfield Units. The average accuracy of Grayscale, Attenuation, and Color methods was 58, 87, and 91% (p < 0.001), respectively. Inter-observer agreement was poor for Grayscale (ICC: 0.20; 95% CI 0.12, 0.28) and excellent for both Attenuation (ICC: 0.85; 95% CI 0.73, 0.91) and Color methods (ICC: 0.87; 95% CI 0.83, 0.90). CONCLUSION: Detection of low spinal bone density using colored abdominal CT images was highly accurate and reproducible.

Precision analysis of a quantitative CT liver surface nodularity score.

PURPOSE: To evaluate precision of a software-based liver surface nodularity (LSN) score derived from CT images. METHODS: An anthropomorphic CT phantom was constructed with simulated liver containing smooth and nodular segments at the surface and simulated visceral and subcutaneous fat components. The phantom was scanned multiple times on a single CT scanner with adjustment of image acquisition and reconstruction parameters (N = 34) and on 22 different CT scanners from 4 manufacturers at 12 imaging centers. LSN scores were obtained using a software-based method. Repeatability and reproducibility were evaluated by intraclass correlation (ICC) and coefficient of variation. Using abdominal CT images from 68 patients with various stages of chronic liver disease, inter-observer agreement and test-retest repeatability among 12 readers assessing LSN by software- vs. visual-based scoring methods were evaluated by ICC. RESULTS: There was excellent repeatability of LSN scores (ICC:0.79-0.99) using the CT phantom and routine image acquisition and reconstruction parameters (kVp 100-140, mA 200-400, and auto-mA, section thickness 1.25-5.0 mm, field of view 35-50 cm, and smooth or standard kernels). There was excellent reproducibility (smooth ICC: 0.97; 95% CI 0.95, 0.99; CV: 7%; nodular ICC: 0.94; 95% CI 0.89, 0.97; CV: 8%) for LSN scores derived from CT images from 22 different scanners. Inter-observer agreement for the software-based LSN scoring method was excellent (ICC: 0.84; 95% CI 0.79, 0.88; CV: 28%) vs. good for the visual-based method (ICC: 0.61; 95% CI 0.51, 0.69; CV: 43%). Test-retest repeatability for the software-based LSN scoring method was excellent (ICC: 0.82; 95% CI 0.79, 0.84; CV: 12%). CONCLUSION: The software-based LSN score is a quantitative CT imaging biomarker with excellent repeatability, reproducibility, inter-observer agreement, and test-retest repeatability.

Endovascular management of chronic total occlusions of the inferior vena cava and iliac veins.

OBJECTIVE: Percutaneous recanalization and stenting is currently the standard of care for symptomatic chronic total occlusions (CTOs) of the iliofemoral veins. CTO lesions involving the inferior vena cava (IVC) present a more complex patient subset. In this series we describe our single-center experience with endovascular recanalization of symptomatic occlusions of the IVC. METHODS: Patients were evaluated with duplex ultrasound imaging, venous function tests, and venography before intervention. Occluded segments were recanalized, balloon dilated, and stented. The basic stent technique modified over time to accommodate the iliocaval junction, presence of IVC filters, and lesions extending to the renal veins and atrium. RESULTS: Between November 2000 and August 2015, 71 patients (41 men [58%]) underwent IVC endovascular recanalization procedures for symptomatic chronic IVC occlusions. Patients were an average age of 51 years (range, 23-77 years). Underlying contributing factors for venous occlusion included IVC filter occlusion in 38 (54%), caval ligation/clipping in 4 (6%), and hypercoagulable disorder in 27 (38%). The technical success rate was 85% (n = 60). The proximal extent of the stents were infrarenal in 40 (67%), suprarenal in 11 (18%), or intrathoracic in 9 (15%). There was minimal perioperative morbidity (2 hematomas, 1 renal failure) and no postoperative mortality. Average follow-up was 48.0 ± 43.3 months (range, 6-172 months). Primary, primary assisted, and secondary patency rates at 60 months were 52%, 85%, and 93%, respectively. Significant improvement in pain and swelling was seen in 91% and 83%, respectively; and complete cumulative relief of pain and swelling was 66% and 41% respectively. Ulcers were present in 18 patients and healed completely without recurrence in 14 (78%) after recanalization. The Venous Clinical Severity Score was 8.4 ± 5.1 (range, 4-27) before the intervention and 3.9 ± 3.2 (range, 0-14) after the intervention (P < .001). CONCLUSIONS: Endovascular recanalization of chronic total IVC occlusions can be performed with minimal morbidity and mortality. When successful, symptoms can be substantially improved, with excellent patency.

Deep venous thrombosis associated with caval extension of iliac stents.

BACKGROUND: It is generally difficult to place an iliac vein stent precisely at the iliocaval junction with venographic control or even with intravascular ultrasound guidance. Furthermore, mechanical properties of the Wallstent (Boston Scientific, Marlborough, Mass) can predispose precisely placed stents to distal displacement or stent collapse. Our center has thus advocated extending Wallstents 3 to 5 cm into the inferior vena cava to prevent complications of missed proximal lesions or stent migration. This technique has gradually been accepted, and concerns of jailing of contralateral flow were not initially recognized. We analyzed deep venous thrombosis (DVT) incidence following iliocaval stenting with two alternative techniques: (1) Wallstents with 3- to 5-cm extension into the inferior vena cava; and (2) a modified Z-stent (Cook Medical, Bloomington, Ind) technique, in which overlapping Wallstents end at the iliac confluence and caval extension is performed with a Z-stent placed at the top of the stack. The function of the Z-stent is to provide improved radial force at the iliocaval confluence and to prevent jailing of contralateral flow with larger stent interstices. METHODS: There were 755 limbs with consecutive Wallstent caval extensions (2006-2010) and 982 limbs with Z-stent extensions (2011-2015) analyzed for DVT incidence postoperatively. RESULTS: Demographics were similar for both groups. Mean age was 56 and 58 years in the Wallstent and Z-stent groups, respectively. There was a female predominance (Wallstent, 69%; Z-stent, 67%) and a higher incidence of left-sided disease (Wallstent, 66%; Z-stent, 56%) in both groups. There was a slightly higher incidence of post-thrombotic disease in the Z-stent subgroup (Wallstent, 53%; Z-stent, 68%). Cumulative freedom from contralateral DVT was 99% and 90% in the Z-stent and Wallstent groups, respectively (P < .001) during the 5 years following stent placement. However, all three patients with DVT contralateral to a Z-stent actually had high placement of the Wallstent across the confluence. Thus, no patients with proper Z-stent technique had a contralateral DVT. Cumulative freedom from ipsilateral DVT was 97% and 82% in the Z-stent and Wallstent groups, respectively (P < .001) during the 5 years following stent placement. The decrease in incidence of ipsilateral DVT appeared to be attributable to decreased missed distal lesions with increased operator experience and not attributable to the Z-stent itself. CONCLUSIONS: Contralateral DVT incidence was significantly lower with the Z-stent modification. In addition, the Z-stent modification provides greater radial strength at the iliac-caval confluence and simplifies simultaneous or sequential bilateral stenting. Use of proper technique and intravascular ultrasound is essential to limit the incidence of ipsilateral DVT.