122 research outputs found
A strategy for probing the evolution of crystallization processes by low-temperature solid-state NMR and dynamic nuclear polarization
Crystallization plays an important role in many areas, and to derive a fundamental understanding of crystallization processes, it is essential to understand the sequence of solid phases produced as a function of time. Here, we introduce a new NMR strategy for studying the time evolution of crystallization processes, in which the crystallizing system is quenched rapidly to low temperature at specific time points during crystallization. The crystallized phase present within the resultant “frozen solution” may be investigated in detail using a range of sophisticated NMR techniques. The low temperatures involved allow dynamic nuclear polarization (DNP) to be exploited to enhance the signal intensity in the solid-state NMR measurements, which is advantageous for detection and structural characterization of transient forms that are present only in small quantities. This work opens up the prospect of studying the very early stages of crystallization, at which the amount of solid phase present is intrinsically low
Las frágiles y peligrosas medusas
International audienceIntroduction: Our aim was to explore the prognostic value of anthropometric parameters in patients treated with nivolumab for stage IV non-small cell lung cancer (NSCLC). Methods: We retrospectively included 55 patients with NSCLC treated by nivolumab with a pretreatment 18FDG positron emission tomography coupled with computed tomography (PET/CT). Anthropometric parameters were measured on the CT of PET/CT by in-house software (Anthropometer3D) allowing an automatic multi-slice measurement of Lean Body Mass (LBM), Fat Body Mass (FBM), Muscle Body Mass (MBM), Visceral Fat Mass (VFM) and Sub-cutaneous Fat Mass (SCFM). Clinical and tumor parameters were also retrieved. Receiver operator characteristics (ROC) analysis was performed and overall survival at 1 year was studied using Kaplan-Meier and Cox analysis. Results: FBM and SCFM were highly correlated (ρ = 0.99). In ROC analysis, only FBM, SCFM, VFM, body mass index (BMI) and metabolic tumor volume (MTV) had an area under the curve (AUC) significantly higher than 0.5. In Kaplan-Meier analysis using medians as cut-offs, prognosis was worse for patients with low SCFM (<5.69 kg/m2; p = 0.04, survivors 41% vs 75%). In Cox univariate analysis using continuous values, BMI (HR = 0.84, p= 0.007), SCFM (HR = 0.75, p = 0.003) and FBM (HR = 0.80, p= 0.004) were significant prognostic factors. In multivariate analysis using clinical parameters (age, gender, WHO performance status, number prior regimens) and SCFM, only SCFM was significantly associated with poor survival (HR = 0.75, p = 0.006). Conclusions: SCFM is a significant prognosis factor of stage IV NSCLC treated by nivolumab
Exploiting solid-state dynamic nuclear polarization NMR spectroscopy to establish the spatial distribution of polymorphic phases in a solid material
Solid-state DNP NMR can enhance the ability to detect minor amounts of solid phases within heterogenous materials. Here we demonstrate that NMR contrast based on transport of DNP-enhanced polarization can be exploited in the challenging case of early detection of a small amount of a minor polymorphic phase within a major polymorph, and we show that this approach can yield quantitative information on the spatial distribution of the two polymorphs. We focus on the detection of a minor amount (<4%) of polymorph III of m-aminobenzoic acid within a powder sample of polymorph I at natural isotopic abundance. Based on proposed models of the spatial distribution of the two polymorphs, simulations of 1H spin diffusion allow NMR data to be calculated for each model as a function of particle size and the relative amounts of the polymorphs. Comparison between simulated and experimental NMR data allows the model(s) best representing the spatial distribution of the polymorphs in the system to be established
Monitoring crystallization processes in confined porous materials by dynamic nuclear polarization solid-state nuclear magnetic resonance
Establishing mechanistic understanding of crystallization processes at the molecular level is challenging, as it requires both the detection of transient solid phases and monitoring the evolution of both liquid and solid phases as a function of time. Here, we demonstrate the application of dynamic nuclear polarization (DNP) enhanced NMR spectroscopy to study crystallization under nanoscopic confinement, revealing a viable approach to interrogate different stages of crystallization processes. We focus on crystallization of glycine within the nanometric pores (7–8 nm) of a tailored mesoporous SBA-15 silica material with wall-embedded TEMPO radicals. The results show that the early stages of crystallization, characterized by the transition from the solution phase to the first crystalline phase, are straightforwardly observed using this experimental strategy. Importantly, the NMR sensitivity enhancement provided by DNP allows the detection of intermediate phases that would not be observable using standard solid-state NMR experiments. Our results also show that the metastable β polymorph of glycine, which has only transient existence under bulk crystallization conditions, remains trapped within the pores of the mesoporous SBA-15 silica material for more than 200 days
Insights into the crystallization and structural evolution of glycine dihydrate by in situ solid-state NMR spectroscopy
In situ solid‐state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid‐state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the β polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently
Nouvelles modalités d’imagerie pour la radiothérapie : imagerie fonctionnelle et moléculaire
International audienceFunctional imaging with positron emission tomography (PET) is interesting to optimize radiotherapy planning, and probably to perform dose redistribution in many cancers. However, in 2015, fluorodeoxyglucose (FDG)-PET is validated only for therapy planning for lung cancer. The interest of dose painting, PET in non-lung cancers, the interest of other tracers (even PET hypoxia tracers), DW-MRI, and PET-MR for radiotherapy needs to be demonstrated in prospective multicentric phase III studies on large series of patients
NMR DOSY (comparison of the processing methods and chemical exchange measurements)
Cette thèse présente les applications de la Résonance Magnétique Nucléaire à l'étude du phénomène d'auto-diffusion. Après une introduction aux concepts théoriques de la mesure du coefficient d'auto-diffusion par RMN, les méthodes Pulsed Gradient Spin Echo (RMN PGSE) et Diffusion Ordered SpectroscopY (RMN DOSY) ont été décrites. La thèse s'articule en deux parties principales traitant respectivement de l'analyse des mélanges chimiques et de la perturbation induite par l'échange chimique sur les expériences de RMN diffusionnelle. Dans la première partie on introduit les limitations du traitement du signal des expériences de RMN PGSE et RMN DOSY, qui sont reliées aux problèmes mathématiques de la transformée de Laplace inverse. Dans la seconde partie, on présente les effets de l'échange chimique sur les expériences RMN PGSE et RMN DOSY et comment cet effet peut être utilisé pour mesurer précisément la constante d'échangeThis thesis can be viewed as the state-of-the-art of Diffusion Ordered NMR SpectroscopY (DOSY). More precisely we described various approaches to analyze the data so that the information obtained from the mixture analysis can be maximized. The limitations of the different methods and the perturbation arising from chemical exchange are also discussed. In the first part of the manuscript, we describe the numerical problems arising from NMR diffusion data processing and compare several methods available in the literature for avoiding such problems. In addition, pulse sequences and methodologies, will be discussed herein. Finally, we describe the perturbation induced by the chemical exchange on NMR diffusion experiments and how this perturbation can be used to extract precisely the exchange rate constant. With the help of these techniques, the hydration properties of the pyrimidine bases have been probedAIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF
Place de l’imagerie fonctionnelle dans la définition des volumes cible en cancérologie pulmonaire
International audienc
How to use PET/CT in the evaluation of response to radiotherapy.
International audienceRadiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI
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