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International audience; Bispidine (3,7-diazabicyclo[3.3.1]nonane) provides a rigid and preorganized scaffold that is particularly interesting for the stable and inert complexation of metal ions, especially for their application in medical imaging. In this study, we present the synthesis of two bispidine ligands with N-methanephosphonate (H4L1) and N-methanecarboxylate (H3L2) substituents as well as the physico-chemical properties of the corresponding Mn2+ and Zn2+ complexes. The two complexes [Mn(L-1)](2- )and [Mn(L-2)](-) have relatively moderate thermodynamic stability constants according to potentiometric titration data. However, they both display an exceptional kinetic inertness, as assessed by transmetallation experiments in the presence of 50 equiv excess of Zn2+, showing only similar to 40 and 20% of dissociation for [Mn(L-1)](2- ) and [Mn(L-2)](-), respectively, after 150 days at pH 6 and 37°C. Proton relaxivities amount to r(1 )= 4.31 mM(-1 )s(-1 )([Mn(L-1)](2-)) and 3.64 mM(-1) s(-1 )([Mn(L-2)](-)) at 20 MHz, 25°C, and are remarkable for Mn2+ complexes with one inner-sphere water molecule (q = 1); they are comparable to that of the commercial contrast agent [Gd(DOTA)(H2O)](-). The presence of one inner-sphere water molecule and an associative water exchange mechanism was confirmed by temperature-dependent transverse O-17 relaxation rate measurements, which yielded k(ex)(298) = 0.12 x 10(7) and 5.5 x 10(7) s(-1 )for the water exchange rate of the phosphonate and the carboxylate complex, respectively. In addition, radiolabeling experiments with Mn-52 were also performed with H-2(L-1)(2-) showing excellent radiolabeling properties and quantitative complexation at pH 7 in 15 min at room temperature as well as excellent stability of the complex in various biological media over 24 h.

International audience; Drug-loaded liposomes are typical examples of nanomedicine. We show here that doxorubicin, the anti-cancer agent in the liposomal drug Doxil ® , can sensitize Ytterbium (Yb 3+ ) and generate its near infrared (NIR) emission. When doxorubicin and amphiphilic Yb 3+ chelates are incorporated into liposomes, the sensitized emission of Yb 3+ is dependent on the integrity of the particles which can be used to monitor drug release. We also established the first demonstration that the NIR Yb 3+ emission signal is observable in living mice following intratumoral injection of the Yb 3+ -doxorubicin-liposomes, using a commercial macroscopic setup equipped with a near-infrared camera.

O objetivo deste artigo é analisar as possibilidades pedagógicas para um ensino que favoreça o desenvolvimento do pensamento algébrico desde os primeiros anos, assumindo a Base Nacional Comum Curricular (BNCC) como ponto de partida e pautado em literatura recente acerca do tema. Trata-se de um ensaio em que são apresentados alguns aportes teóricos os quais evidenciam que a melhora das capacidades de raciocínio e comunicação de ideias progressivamente mais abstratas está relacionada com desafios e explorações a que os alunos são expostos desde bem pequenos em atividades que valorizam a criatividade e a resolução de problemas. Destacamos, ainda, que vários pesquisadores têm indicado a importância do estudo de padrões e regularidades em Early Algebra, considerando o desenvolvimento do pensamento algébrico como etapa fundamental para o aprendizado da álgebra. O texto apresenta algumas ideias de trabalho pedagógico com padrões e regularidades para a educação infantil e os anos iniciais do ensino fundamental com base nas indicações da BNCC e aponta para a importância de destacar esse tema na formação de professores.

With the purpose of researching the relationships between poetry and document arising from the concept of the archive, this study proposes material analysis of the work produced by the Por-tuguese experimental poet António Aragão with press clippings and establishes dialogues with other examples of collage and montage developed in the 20th-century and today.

International audience; Amyloid forms of many different proteins have been long identified as relevant biomarkers in important pathologies with high societal impact, including Aβ in Alzheimer's disease, amylin in type 2 diabetes, α-synuclein in Parkinson's disease, etc. With over eighty novel complexes reported in the last six years, metal-based agents designed for the detection of such amyloid fibrils represent a rapidly growing field in molecular imaging. While the majority of these examples are radiocomplexes for nuclear imaging and focus on the detection of Aβ in Alzheimer's disease, there is increasing interest in other peptides and pathologies, and few studies are also directed at magnetic resonance imaging probes. In this review, we survey the recent literature according to the chemical nature of the amyloid recognition moieties, most of which are derived from a few basic structures, including benzothiazole, benzofuran or stilbene. Relationships between chemical structure and amyloid binding properties and biodistribution, in particular brain delivery and brain clearance, are outlined in order to help further work in this emerging area of research.

Magnetic resonance imaging (MRI) is one of the most powerful imaging tools due to its very high resolution and the possibility of imaging the whole body. Its lack of sensitivity can be compensated for by the use of a contrast agent (CA), typically Gd3+-based complexes. Since most of the commercially available Gd3+-based CAs have no specificity, research in the area of molecular imaging (i.e. biomarkers detection) has been the subject of growing interest in the past decades. This leads to the design of more powerful CAs, which should enable early detection of disease and personalised medicine. In the first part of this chapter, recent advances in the detection of endogenous triggers (pH, cations, enzymes) will be described. In the second part, we will focus on the design of targeted CAs to detect deregulated proteins or receptors. Finally, we will concentrate on theranostics, i.e. combining an imaging technique with therapy. This offers endless possibilities for monitoring treatment efficacy in real-time or in the follow-up of therapies. The combination of MRI with different therapies (chemotherapy, photodynamic therapy and radiation therapy) will be described. Rather than an exhaustive review of each topic, this chapter aims at describing the state-of-the-art of the different methods with selected examples, together with strengths and limitations of those CAs.

International audience; Porous materials, such as zeolites, have great potential for biomedical applications, thanks to their ability to accommodate positively charged metal-ions and their facile surface functionalization. Although the latter aspect is important to endow the nanoparticles with chemical/colloidal stability and desired biological properties, the possibility for simple ion-exchange enables easy switching between imaging modalities and/or combination with therapy, depending on the envisioned application. In this study, the nanozeolite Linde type L (LTL) with already confirmed magnetic resonance imaging properties, generated by the paramagnetic gadolinium (GdIII) in the inner cavities, was successfully radiolabeled with a positron emission tomography (PET)-tracer zirconium-89 (89Zr). Thereby, exploiting 89Zr-chloride resulted in a slightly higher radiolabeling in the inner cavities compared to the commonly used 89Zr-oxalate, which apparently remained on the surface of LTL. Intravenous injection of PEGylated 89Zr/GdIII-LTL in healthy mice allowed for PET-computed tomography evaluation, revealing initial lung uptake followed by gradual migration of LTL to the liver and spleen. Ex vivo biodistribution confirmed the in vivo stability and integrity of the proposed multimodal probe by demonstrating the original metal/Si ratio being preserved in the organs. These findings reveal beneficial biological behavior of the nanozeolite LTL and hence open the door for follow-up theranostic studies by exploiting the immense variety of metal-based radioisotopes.

International audience; Dysregulated remodeling of the extracellular matrix (ECM) can lead to excessive accumulation of ECM proteins (primarily collagen, elastin/ tropoelastin, fibronectin and fibrin) resulting in tissue fibrosis. In many pathologies, changes in the molecular pattern of ECM components have been related to the progression and severity of fibrosis. Thus, magnetic resonance imaging (MRI) probes sensing specific ECM components hold promise for accurate staging of fibrotic diseases. This paper focuses on gadolinium-based contrast agents (GBCA) targeted to ECM components, including structural proteins and enzymes. According to available examples, they can be grouped into: 1) GBCA conjugated to targeting vectors that recognize and noncovalently bind to specific sites on the molecular target; 2) GBCA carrying a reactive chemical function able to bind covalently to the complementary chemical function of the molecular target; and 3) enzyme-responsive probes, whose relaxivity and pharmacokinetics change after enzymatic processing. Pros and cons of each approach are discussed.

International audience; Dysfunctional elastin turnover plays a major role in the progression of atherosclerotic plaques. Failure of tropoelastin cross-linking into mature elastin leads to the accumulation of tropoelastin within the growing plaque, increasing its instability. Here we present Gd4-TESMA, an MRI contrast agent specifically designed for molecular imaging of tropoelastin within plaques. Gd4-TESMA is a tetrameric probe composed of a tropoelastin-binding peptide (the VVGS-peptide) conjugated with four Gd(III)-DOTA-monoamide chelates. It shows a relaxivity per molecule of 34.0 ± 0.8 mM-1 s-1 (20 MHz, 298 K, pH 7.2), a good binding affinity to tropoelastin (KD = 41 ± 12 μM), and a serum half-life longer than 2 h. Gd4-TESMA accumulates specifically in atherosclerotic plaques in the ApoE-/- murine model of plaque progression, with 2 h persistence of contrast enhancement. As compared to the monomeric counterpart (Gd-TESMA), the tetrameric Gd4-TESMA probe shows a clear advantage regarding both sensitivity and imaging time window, allowing for a better characterization of atherosclerotic plaques.

A presente investigação pretende analisar obras da Poesia Experimental Portuguesa, iniciada na década de 1960, usando tópicos da visualidade que contribuam para uma reflexão alargada sobre esta produção no contexto interdisciplinar e internacional da Neovanguarda. O corpus de obras experimentais organiza-se em dois grupos para implementar métodos complementares de leitura, longitudinais e transversais, que recorrem a várias estratégias visuais. Um grupo tem um critério autoral e examina sobretudo publicações individuais de Poesia Visual de Ana Hatherly e António Aragão. O outro grupo privilegia afinidades processuais e temáticas utilizadas por diferentes autores do Experimentalismo. Como tal, este estudo tem como o principal objectivo perceber as implicações dos recursos materiais e visuais da Poesia Experimental portuguesa nos modos como as suas obras se dão a ler e a ver. The current research intends to analyze works of Portuguese Experimental Poetry, a movement initiated in the 1960s, using topics of visuality in order to enable a broader reflection upon this production within the interdisciplinary and international context of the Neo-avant-garde. The set of Experimental works is organized in two main groups to allow complementary reading methodologies, longitudinal and transversal, that make use of several visual strategies. One group is author-based and examines mostly individual editions of Visual Poetry published by Ana Hatherly and António Aragão. The other group is focused on specific procedural and thematic affinities shared by different Experimental practices. Therefore, the ultimate purpose of this study is to understand how material and visual resources used in Experimental Poetry widen the ways in which its own works offer themselves to the reader and to the viewer.

UIDB/00657/2020 UIDP/00657/2020 Com o intuito de indagar as relações entre poesia e documento suscitadas pela noção de arquivo, este estudo propõe leituras materiais de obras do poeta experimental português António Aragão realizadas com recortes de imprensa e estabelece diálogos com outros exemplos de colagem e montagem produzidos durante o século XX e a atualidade. With the purpose of researching the relationships between poetry and document arising from the concept of the archive, this study proposes material analysis of the work produced by the Por-tuguese experimental poet António Aragão with press clippings and establishes dialogues with other examples of collage and montage developed in the 20th-century and today publishersversion published

International audience; Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents. The attachment of a metal complex to amyloid recognition units typically leads to a decrease in peptide affinity. We show here that by separating a macrocyclic GdL chelate and a PiB targeting unit with a long hydrophobic C10 linker, it is possible to attain nanomolar affinities for both Aβ 1‐40 ( K d = 4.4 nM) and amylin ( K d = 4.5 nM), implicated respectively in Alzheimer’s disease and diabetes. The Scatchard analysis of surface plasmon resonance data obtained for a series of amphiphilic, PiB derivative GdL complexes indicate that their Aβ 1‐40 or amylin binding affinity varies with their concentration, thus micellar aggregation state. The GdL chelates also affect peptide aggregation kinetics, as probed by thioflavin‐T fluorescence assays. A 2D NMR study allowed identifying that the hydrophilic region of Aβ 1‐40 is involved in the interaction between the monomer peptide and the Gd 3+ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using 111 In labelled analogues. Their pancreatic uptake, ~3%ID/g, is promising to envisage amylin imaging in diabetic animals.

The search for more biocompatible alternatives to Gd

International audience; The search for more biocompatible alternatives to Gd 3+-based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn 2+ chelates. Given the labile nature of Mn 2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L1 endows its Mn 2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140 days in the presence of 50 eq. of Zn 2+ (37°C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL1 (4.28 mM-1 s-1 at 25°C, 20 MHz) is remarkable for a monohydrated, small Mn 2+ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL1. Additionally, L1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.

Aims Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific magnetic resonance contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed. Methods and results We utilized the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilation and performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) and T1 mapping at 3 T, with subsequent ex vivo validation. In a cross-sectional study (n = 66; control = 11, infused = 55) we found that Gd-TESMA enhanced MRI was elevated and confined to dilated aortic segments (control: LGE=0.13 ± 0.04 mm2, control R1= 1.1 ± 0.05 s-1 vs. dilated LGE=1.0 ± 0.4 mm2, dilated R1 =2.4 ± 0.9 s-1) and was greater in segments with medium (8.0 ± 3.8 mm3) and large (10.4 ± 4.1 mm3) compared to small (3.6 ± 2.1 mm3) vessel volume. Furthermore, a proof-of-principle longitudinal study (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expression in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment with pravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87 ± 0.3 mm2 vs. 1.0 ± 0.44 mm2) or aortic dilation (4.86 ± 2.44 mm3 vs. 4.0 ± 3.6 mm3). Importantly, Gd-TESMA-enhanced MRI identified accumulation of tropoelastin in excised human aneurysmal tissue (n = 4), which was confirmed histologically. Conclusion Tropoelastin MRI identifies dysfunctional matrix remodelling that is specifically expressed in regions of aortic aneurysm or dissection and correlates with the development and rate of aortic expansion. Thus, it may provide an additive imaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with established aortopathy.

Background Candidemia is a nosocomial infection of increasing importance, associated with high morbidity and mortality. The aim of this study is to describe the species distribution, risk factors, management and outcomes of patients with candidemia. Methods We conducted a retrospective study at Centro Hospitalar Universitario de Sao Joao, Portugal, between January 2016 and December 2017. Results A total of 117 candidemia episodes (n = 114 patients) were included. Median age was 65 years, with an increased prevalence of older ages. Candida albicans (51.3%) was the most prevalent species, followed by C. glabrata (22.2%), C. parapsilosis (15.4%), C. tropicalis (4.3%) and C. lusitaniae (2.6%). Forty-two patients (35.9%) did not receive antifungal drugs after diagnosis of candidemia. Echinocandins were used as first-line drug therapy in half of the treated patients (50.7%). The median EQUAL Candida Score was 6/17 (IQR 6-9) for patients without central venous catheter (CVC) and 11/20 (IQR 6-14) for patients with CVC. The 30 days-mortality was 31,6% and was not significantly associated with the timing of antifungal therapy and the EQUAL Candida Score. Conclusion The distribution of Candida species has changed in recent years, with an increase in the proportion of C. albicans and C. glabrata. Rapid diagnostic tests, empiric antifungal therapy and source control are essential to improve the prognosis of patients with candidemia. More multicentric prospective studies are needed to evaluate the association of mortality with the timing of antifungal therapy or the EQUAL Candida Score.

International audience; Aggregation of misfolded proteins and progressive polymerization of otherwise soluble proteins is a common hallmark of a wide range of highly debilitating and increasingly prevalent diseases, including amyotrophic lateral sclerosis, cerebral amyloid angiopathy, type II diabetes and Parkinson's, Huntington's and Alzheimer's diseases. There is a growing interest in creating imaging agents to detect such aggregates in various imaging modalities, including PET, SPECT and MRI. We present here an overview of recent efforts from the perspective of early diagnosis of amyloid diseases, with a major focus on Aβ detection and metal complexes bearing PiB units.

Background: Elastolysis and ineffective elastogenesis favor the accumulation of tropoelastin, rather than cross-linked elastin, in atherosclerotic plaques. We developed gadolinium-labeled tropoelastin-specific magnetic resonance contrast agents for tropoelastin imaging in animal models. Methods and Results: Two peptides, VVGSPSAQDEASPLS and YPDHVQYTHY, were selected to target tropoelastin. In vitro binding, relaxivity, and biodistribution experiments enabled characterization of the probes and selecting the best candidate for in vivo magnetic resonance imaging. Magnetic resonance imaging was performed in atherosclerotic apolipoprotein E–deficient mice and New Zealand white rabbits with stable and rupture-prone plaques using a gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent. In addition, human carotid endarterectomy specimens were imaged ex vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and cross-linked elastin (64%±7% versus 1%±2%; P =0.001), had high in vitro relaxivity in solution (r 1-free =11.7±0.6 [mmol/L] −1 s −1 , r 1-bound to tropoelastin =44±1 [mmol/L] − 1 s − 1 ), and favorable pharmacokinetics. In vivo mice vascular enhancement (4 weeks=0.13±0.007 mm 2 , 8 weeks=0.22±0.01 mm 2 , 12 weeks=0.33±0.01 mm 2 ; P 1 relaxation rate (4 weeks=[0.90±0.01]/s, 8 weeks=[1.40±0.03]/s, 12 weeks=[1.87±0.04]/s; P 2 ; R 1 =[1.37±0.03]/s) and control (0.10±0.005 mm 2 ; R 1 =[0.87±0.05]/s) mice showed less enhancement. Rupture-prone rabbit plaques had higher R 1 relaxation rate compared with stale plaques (R 1 =[2.26±0.1]/s versus R 1 =[1.43±0.02]/s; P =0.001) after administration of the gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent that allowed detection of rupture-prone plaques with high sensitivity (84.4%) and specificity (92.3%). Increased vascular R 1 relaxation rate was observed in carotid endarterectomy plaques after soaking (R 1pre =[1.1±0.26]/s versus R 1post =[3.0±0.1]/s; P =0.01). Ex vivo analyses confirmed the magnetic resonance imaging findings and showed uptake of the contrast agent to be specific for tropoelastin. Conclusions: Magnetic resonance imaging of tropoelastin provides a novel biomarker for atherosclerotic plaque progression and instability.

We propose quantitative assessment of zinc by combining nuclear and MR imaging. We use a cocktail of a Gd3+-complex providing a Zn2+-dependent MRI response and its 165Er3+ analogue allowing for concentration assessment. 165Er is readily obtained in a cyclotron and purified, which is indispensable for successful quantification of metal ions.

Este artigo propoe uma analise do livro Mais Exactamente P(r)o(bl)emas (1968), escrito pelo poeta experimental portugues Antonio Aragao, com base numa abordagem material que utiliza os conceitos de colagem, montagem e assemblagem.

Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder leading to progressive and irreversible decline of cognitive functions. Together with neurofibrillary tangles, the formation of brain extracellular plaques containing amyloid-β peptides is a major neuropathological hallmark associated with AD. The development of clinical imaging techniques for early detection of AD is a primary health objective. We present here an overview of recent progress in the chemistry of molecular probes for the in vivo MRI detection of Aβ deposits in the brain to improve early diagnosis of AD.

We propose quantitative assessment of zinc by combining nuclear and MR imaging. We use a cocktail of a Gd3+-complex providing a Zn2+-dependent MRI response and its 165Er3+ analogue allowing for concentration assessment. 165Er is readily obtained in a cyclotron and purified, which is indispensable for successful quantification of metal ions.

International audience; Lanthanide complexes have attracted much attention in the biomedical field, and today various imaging applications make use of their versatile magnetic and luminescence properties. In this minireview, we give insight into the mechanistic aspects that allow modulation of the relaxation or chemical exchange saturation transfer (CEST) features, and thus the magnetic resonance imaging (MRI) efficiency of paramagnetic lanthanide chelates in order to create agents that are capable of providing an MRI response as a function of a specific biomarker. We focus on the detection of neurotransmitters, enzymatic activities, and amyloid peptides. We also describe two selected theranostic strategies: 1) a novel approach directed at monitoring drug release from liponanoparticles and 2) molecular or nanoparticle probes for the MRI visualization of photosensitizer delivery in photodynamic therapy.

International audience; A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r1 relaxivity of 23.4 mM-1s-1 at 3T, 25 oC) is a photo-activated cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation.

This article belongs to the Special Issue Targeted Drug Delivery., Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes., This research was funded by FCT (Portuguese Foundation for Science and Technology), grant numbers EXCL/QEQ-MED/0233/2012, UID/Multi/04349/2013 and PTDC/MED-QUI/29649/2017. CFGCG and MMCAC thank FCT and FEDER through the COMPETE Program for funding the CQC (UID/QUI/00313/2013 and PEst-OE/QUI/UI0313/2014). P.L-L. thanks Ministry of Economy, Industry and Competitiviy for SAF2017-83043-R, and Comunity of Madrid, FEDER and FSE for S2017/BMD-3688.

Background— The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. Methods and Results— To induce AAAs, ApoE –/– mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Conclusions— Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.

International audience

Despite advances in prevention, risk assessment and treatment, coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western countries. The lion’s share is due to acute coronary syndromes (ACS), which are predominantly triggered by plaque rupture or erosion and subsequent coronary thrombosis. As the majority of vulnerable plaques does not cause a significant stenosis, due to expansive remodeling, and are rather defined by their composition and biological activity, detection of vulnerable plaques with x-ray angiography has shown little success. Non-invasive vulnerable plaque detection by identifying biological features that have been associated with plaque progression, destabilization and rupture may therefore be more appropriate and may allow earlier detection, more aggressive treatment and monitoring of treatment response. MR molecular imaging with target specific molecular probes has shown great promise for the noninvasive in vivo visualization of biological processes at the molecular and cellular level in animals and humans. Compared to other imaging modalities; MRI can provide excellent spatial resolution; high soft tissue contrast and has the ability to simultaneously image anatomy; function as well as biological tissue composition and activity.

International audience; We report first prototypes of responsive lanthanide(III) complexes that can be monitored independently in three complementary imaging modalities. Through the appropriate choice of lanthanide(III) cations, the same reactive ligand can be used to form complexes providing detection by (i) visible (Tb3+) and near-infrared (Yb3+) luminescence, (ii) PARACEST- (Tb3+, Yb3+), or (iii) T1-weighted (Gd3+) MRI. The use of lanthanide(III) ions of different natures for these imaging modalities induces only a minor change in the structure of complexes that are therefore expected to have a single biodistribution and cytotoxicity.

Determining the shelf life has become a factor of major importance in the development of foods designed to meet consumer demands in terms of quality and safety. The goal of the present study was to investigate the shelf life of vacuum-packed dried tomatoes, stored at both room and refrigeration temperature (4 °C) for a period of 180 days. The following determinations were performed during the storage period studied: microbiological analysis, instrumental color, lycopene, and ascorbic acid. Sorption isotherms were determined at both temperatures (room temperature and 4 °C). The microbiological quality of vacuum-packed dried tomatoes remained unchanged during 180 days for the refrigerated samples and 90 days for the samples stored at room temperature. The rate constant (k) of lycopene degradation of the refrigerated samples and the samples stored at room temperature was 3.209 × 10−5 and 12.994 × 10−5/day, respectively. The rate constant (k) of ascorbic acid degradation was 3.339 × 10−4/day for cold storage and 76.655 × 10−4/day for storage at room temperature. The tomatoes stored at room temperature were subjected to analysis over 90 days of storage, period after which both the appearance and sensory characteristics of the product fell below the levels of consumer acceptability. As for the tomatoes stored at refrigeration temperature, the original sensory characteristics were maintained throughout the entire storage period of 180 days.