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Hydrophobic-core PEGylated graft copolymer-stabilized nanoparticles composed of insoluble non-nucleoside reverse transcriptase inhibitors exhibit strong anti-HIV activity

Wed, 10/05/2016 - 10:18am

Benzophenone-uracil (BPU) scaffold-derived candidate compounds are efficient non-nucleoside reverse transcriptase inhibitors (NNRTI) with extremely low solubility in water. We proposed to use hydrophobic core (methoxypolyethylene glycol-polylysine) graft copolymer (HC-PGC) technology for stabilizing nanoparticle-based formulations of BPU NNRTI in water. Co-lyophilization of NNRTI/HC-PGC mixtures resulted in dry powders that could be easily reconstituted with the formation of 150-250 nm stable nanoparticles (NP). The NP and HC-PGC were non-toxic in experiments with TZM-bl reporter cells. Nanoparticles containing selected efficient candidate Z107 NNRTI preserved the ability to inhibit HIV-1 reverse transcriptase polymerase activities with no appreciable change of EC50. The formulation with HC-PGC bearing residues of oleic acid resulted in nanoparticles that were nearly identical in anti-HIV-1 potency when compared to Z107 solutions in DMSO (EC50=7.5+/-3.8 vs. 8.2+/-5.1 nM). Therefore, hydrophobic core macromolecular stabilizers form nanoparticles with insoluble NNRTI while preserving the antiviral activity of the drug cargo.

Library based x-ray scatter correction for dedicated cone beam breast CT

Wed, 10/05/2016 - 10:17am

PURPOSE: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability.

METHODS: The authors precompute a scatter library on simplified breast models with different sizes using the geant4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correction on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation.

RESULTS: Since the time-consuming MC simulation for library generation is precomputed, the authors' method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors' method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal views.

CONCLUSIONS: The library-based scatter correction does not require increase in radiation dose or hardware modifications, and it improves over the existing methods on implementation simplicity and computational efficiency. As demonstrated through patient studies, the authors' approach is effective and stable, and is therefore clinically attractive for CBBCT imaging.

Grading of Regional Apposition after Flow-Diverter Treatment (GRAFT): a comparative evaluation of VasoCT and intravascular OCT

Wed, 10/05/2016 - 10:17am

BACKGROUND: Poor vessel wall apposition of flow diverter (FD) stents poses risks for stroke-related complications when treating intracranial aneurysms, necessitating long-term surveillance imaging. To facilitate quantitative evaluation of deployed devices, a novel algorithm is presented that generates intuitive two-dimensional representations of wall apposition from either high-resolution contrast-enhanced cone-beam CT (VasoCT) or intravascular optical coherence tomography (OCT) images.

METHODS: VasoCT and OCT images were obtained after FD implant (n=8 aneurysms) in an experimental sidewall aneurysm model in canines. Surface models of the vessel wall and FD device were extracted, and the distance between them was presented on a two-dimensional flattened map. Maps and cross-sections at potential locations of malapposition detected on VasoCT-based maps were compared. The performance of OCT-based apposition detection was evaluated on manually labeled cross-sections using logistic regression against a thresholded ( > /=0.25 mm) apposition measure.

RESULTS: VasoCT and OCT acquisitions yielded similar Grading of Regional Apposition after Flow-Diverter Treatment (GRAFT) apposition maps. GRAFT maps from VasoCT highlighted 16 potential locations of malapposition, of which two were found to represent malapposed device struts. Logistic regression showed that OCT could detect malapposition with a sensitivity of 98% and a specificity of 81%.

CONCLUSIONS: GRAFT delivered quantitative and visually convenient representations of potential FD malapposition and occasional acute thrombus formation. A powerful combination for future neuroendovascular applications is foreseen with the superior resolution delivered by intravascular OCT.