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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.

Radiology and Global Health: The Case for a New Subspecialty

Mon, 10/03/2016 - 7:20am

In high- and medium-income countries, the use of radiology has grown substantially in the last several decades. But in the developing world, access to medical imaging remains a critical problem. Unlike more structured efforts in the field of global health, interventions in global radiology have been largely unplanned, fragmented and sometimes irrelevant to the needs of the recipient society, and have not resulted in any significant progress. Access to medical imaging around the world remains dismal. There is a therefore a clear and urgent need for the radiology community to develop a vision for global radiology, beginning with defining the scope of the subject and establishing measurable goals. Agreement must be reached to declare global radiology as a bona fide subspecialty of radiology. This should soon be followed by the establishment of divisions of Global Radiology in academic radiology departments. Resident and medical students should be taught how physicians in low -income countries practice medicine without access to adequate radiology. As part of training and electives, residents and medical students should accompany global health teams to countries where the need for radiology services is great. Global scholar exchange and sabbatical opportunities should be offered to staff radiologists. Successful implementation of a unified vision of global radiology has the potential to improve access to medical imaging on a large scale. Radiology journals dedicated to the promotion of global radiology can play an important role in providing forums of discussion, analyses and sharing of field experiences. In this discussion we have attempted to make a case for assigning global radiology a subspecialty status.

UMCCTS Newsletter, September 2016

Fri, 09/30/2016 - 8:24am

This is the September 2016 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

UMCCTS Newsletter, August 2016

Fri, 09/30/2016 - 8:24am

This is the August 2016 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

UMCCTS Newsletter, July 2016

Fri, 09/30/2016 - 8:24am

This is the July 2016 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

UMCCTS Newsletter, June 2016

Fri, 09/30/2016 - 8:24am

This is the June 2016 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

UMCCTS Newsletter, May 2016

Fri, 09/30/2016 - 8:24am

This is the May 2016 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

Treatment of Cancer Pain

Fri, 09/30/2016 - 7:20am

Pain is one of the first concerns most cancer patients express when newly diagnosed or meeting a new physician. They are concerned about how much pain they presently have, how much pain they are likely to experience, and their physicians’ commitment to treating cancer pain. The reality is that many cancer patients will never experience pain during their course and for those that do, the great majority can be well-managed with the tools described in this chapter in Cancer Concepts: A Guidebook for the Non-Oncologist. It is incumbent on every physician to understand the mechanisms of cancer pain and the fundamentals of treating it.