Encapsulation of VEGF₁₆₅ into magnetic PLGA nanocapsules for potential local delivery and bioactivity in human brain endothelial cells

Angiogenesis is an important repairing mechanism in response to ischemia. The administration of proangiogenic proteins is an attractive therapeutic strategy to enhance angiogenesis after an ischemic event. Their labile structures and short circulation times in vivo are the main obstacles that reduce the bioactivity and dosage of such proteins at the target site. We report on poly(D,L-lactic-co-glycolic acid)(PLGA) nanocapsules (diameter < 200 nm) containing bioactive vascular endothelial growth factor-165 (VEGF165) in the inner core and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in the polymeric shell. The system showed good encapsulation efficiencies for both VEGF165 and SPIONs and a sustained protein release over 14 days. In vitro studies confirmed protein bioactivity in the form of significantly increased proliferation in human microvascular brain endothelial cell cultures once the protein was released. Through magnetic resonance imaging (MRI) measurements we demonstrated excellent T2 contrast image properties with r2 values as high as 213 mM-1 s-1. In addition, magnetic VEGF165-loaded PLGA nanocapsules could be displaced and accumulated under an external magnetic field for guiding and retention purposes. We therefore suggest that using VEGF165-loaded magnetic PLGA nanocapsules may become a new targeted protein-delivery strategy in the development of future pro-angiogenic treatments, as for instance those directed to neurorepair after an ischemic event

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI–Dynamic Contrast-Enhanced challenge

PURPOSE: (Formula presented.) has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for (Formula presented.) quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging–Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize (Formula presented.) measurement. METHODS: A framework was created to evaluate (Formula presented.) values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for (Formula presented.) quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' (Formula presented.) values, the applied software, and a standard operating procedure. These were evaluated using the proposed (Formula presented.) score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the (Formula presented.) score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0–1 = lowest–highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in (Formula presented.) analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within (Formula presented.) estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI–Dynamic Contrast-Enhanced challenge

Purpose: K trans has often been proposed as a quantitative imaging biomarker for diagnosis,prognosis,andtreatmentresponseassessmentforvarioustumors.Noneofthe many software tools for K trans quantification are standardized. The ISMRM OpenScience Initiative for Perfusion Imaging–Dynamic Contrast-Enhanced (OSIPI-DCE)challenge was designed to benchmark methods to better help the efforts to standardize K trans measurement. Methods: A framework was created to evaluate K trans values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants’ K trans values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIPIgold score defined with accuracy, repeatability, and reproducibility components. Results: Across the 10 received submissions, the OSIPIgold score ranged from28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively(0–1=lowest–highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. Conclusions: This study reports results from the OSIPI-DCE challenge and high-lights the high inter-software variability within K trans estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology