Automatic evaluation of the Valsalva sinuses from cine-MRI

To be published in Magn Reson Mater PhyInternational audienceAlthough, there is no global consensus on their measurement, MRI appears to be particularly attractive for the study of the sinuses of Valsalva (SV). The purpose of this study was to automatically evaluate the SV from cine-MRI using a standardized method. An automatic method based on mathematical morphology was elaborated to segment the aortic root from cross-sectional cine-MRI, and to detect relevant points, such as the commissures, the cusps and the centre of the SV. The distances between these points allow a metric evaluation of the SV. Our method was tested on synthesized data and 41 patient data sets and radii calculations were compared with manual processing. On the patient data sets, there are excellent correlation and concordance between manual and automatic measurements for images at diastole (r= 0.97; y = 0.97 x + 0.57; p<10-5; mean of differences = 0.2 mm; standard deviation of differences = 2.0 mm) and at systole (r= 0.96; y = 0.96 x + 1.2; p<10-5; mean of differences < 0.1 mm; standard deviation of differences = 2.4 mm). Our automatic method provides reliable morphometric evaluation of the SV. Measures of distances between relevant points allow a precise evaluation of each cusp of the SV. This robust evaluation can be helpful in the follow-up of patients with aortic root diseases

Cancer-Targeting Ultrasmall Silica Nanoparticles for Clinical Translation: Physicochemical Structure and Biological Property Correlations

Although a large body of literature exists on the potential use of nanoparticles for medical applications, the number of probes translated into human clinical trials is remarkably small. A major challenge of particle probe development and their translation is the elucidation of safety profiles associated with their structural complexity, not only in terms of size distribution and heterogeneities in particle composition but also their effects on biological activities and the relationship between particle structure and pharmacokinetics. Here, we report on the synthesis, characterization, and long-term stability of ultrasmall (<10 nm diameter) dual-modality (optical and positron emission tomography) and integrin-targeting silica nanoparticles (cRGDY–PEG–Cy5–C′ dots and ¹²⁴I-(or ¹³¹I-) cRGDY–PEG–Cy5–C′dots) and the extent to which their surface ligand density differentially modulates key in vitro and in vivo biological activities in melanoma models over a range of ligand numbers (i.e., ∼6–18). Gel permeation chromatography, established as an important particle characterization tool, revealed a two-year shelf life for cRGDY–PEG–Cy5–C′ dots. Radiochromatography further demonstrated the necessary radiochemical stability for clinical applications. The results of subsequent ligand density-dependent studies elucidate strong modulations in biological response, including statistically significant increases in integrin-specific targeting and particle uptake, cellular migration and adhesion, renal clearance, and tumor-to-blood ratios with increasing ligand number. We anticipate that nanoprobe characteristics and a better understanding of the structure–function relationships determined in this study will help guide identification of other lead nanoparticle candidates for in vitro and in vivo biological assessments and product translation

Melanocortin‑1 Receptor-Targeting Ultrasmall Silica Nanoparticles for Dual-Modality Human Melanoma Imaging

The poor prognosis associated with malignant melanoma has not changed substantially over the past 30 years. Targeted molecular therapies, such as immunotherapy, have shown promise but suffer from resistance and off-target toxicities, underscoring the need for alternative therapeutic strategies that can be used in combination with existing protocols. Moreover, peptides targeting melanoma-specific markers, like the melanocortin-1 receptor (MC1-R), for imaging and therapy exhibit high renal uptake that limits clinical translation. In the current study, the application of ultrasmall fluorescent (Cy5) silica nanoparticles (C′ dots), conjugated with MC1-R targeting alpha melanocyte stimulating hormone (αMSH) peptides on the polyethylene glycol (PEG) coated surface, is examined for melanoma-selective imaging. αMSH peptide sequences, evaluated for conjugation to the PEG-Cy5-C′ dot nanoparticles, bound to MC1-R with high affinity and targeted melanoma in syngenetic and xenografted melanoma mouse models. Results demonstrated a 10-fold improvement in MC1-R affinity over the native peptide alone following surface attachment of the optimal αMSH peptide. Systematic in vivo studies further demonstrated favorable in vivo renal clearance kinetics as well as receptor-mediated tumor cell internalization of as-developed radiolabeled particle tracers in B16F10 melanoma bearing mice. These findings highlight the ability of αMSH-PEG-Cy5-C′ dots to overcome previous hurdles that prevented clinical translation of peptide and antibody-based melanoma probes and reveal the potential of αMSH-PEG-Cy5-C′ dots for melanoma-selective imaging, image-guided surgery, and therapeutic applications