9 research outputs found

    Influence des composés matriciels sur le signal IRM du cartilage

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    NANCY1-SCD Medecine (545472101) / SudocSudocFranceF

    Designing dedicated rapamycin nanoparticles for articular vectorization: A holistic pharmacological approach

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    International audienceIntroduction: Rapamycin, an immunosuppressant, is a mTOR inhibitor leading to autophagy restoration. It is a candidate (10 μM) for experimental intra-articular (IA) treatment of osteoarthritis (OA), autophagy being defective in OA. Material and methods: We performed in vitro cytotoxicity on human chondrocytes, synoviocytes, and mesenchymal stem cells (MSCs) after 24 h exposure in hypoxia and normoxia with various rapamycin concentrations (10 nM to 100 μM). We then evaluated autophagic (beclin1 and Atg7) and catabolic (MMP13) genes with 10 μM rapamycin exposure for 24 h. We also developed rapamycin-loaded nanoparticles (NPs) for IA injection to assess NPs' cytotoxicity vs free rapamycin. We finally studied in vivo pharmacokinetic parameters of free (IV & IA) or NPs-loaded rapamycin (IA) (10 μM) injections in blood and synovial tissue in rat knees: AUC, T1/2, and MRT. Results: In vitro, we observed the concentrationdependent toxicity of free rapamycin for chondrocytes, synoviocytes, and MSCs. The IC50 was: 68.7, 79.7, and 79.7 μM in normoxia and 79.1, 29.9 and 38.5 μM in hypoxia, respectively. No difference was observed for autophagic genes in the three cellular types, but the IL1β-induced MMP13 level decreased. Rapamycin NPs showed similar dose-dependent toxicity on articular cells. In vivo, we determined (10 μM) an AUC higher for IV free rapamycin than for IA injection (AUCIA free and AUCIA NP), with respectively 4248, 28, and 74 μg/ min/L in blood. We observed a difference between AUCIA free and AUCIA NP (3735 and 10513 μg/min/L) concerning synovium. T1/2 and MRT were higher after NPs than free rapamycin injections: 57.8-5.0 h, vs. 80.6-5.5 h, respectively. Histology revealed no knee injury. Discussion/Conclusion: In vitro, rapamycin (10 μM) did not induce articular cytotoxicity and reduced IL1β's phlogistic effects. Rapamycin NPs did not induce cytotoxicity on articular cells at 10 μM. In vivo, IA administration of 10 μM rapamycin NPs increased its local residency vs. free rapamycin with lower systemic diffusion

    Design of a Four-Channel Surface Receiver Coil Array Without Preamplifiers for the Decoupling Between Elements: Validation for High-Resolution Rat Knee MR Imaging

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    International audienceIn Magnetic Resonance Imaging (MRI), multi-channel coil arrays are increasingly being used to improve Signal-to-Noise Ratio (SNR) in order to increase spatial and/or temporal image resolution. Recent decoupling technique allows conception of two-channel surface transceiver coil arrays; this technique based on common conductor does not require additional preamplifier for the decoupling between elements. In this case the coil array loops are directly connected to the independent transmit/receive switches and preamplifiers of the MR system. Using this common conductor decoupling technique, a topology of a four-channel coil array was developed and described in this paper. A four-channel surface receiver coil array was designed to perform the simultaneous acquisition of both rat knee joints at 7T. Without the use of additional preamplifiers, a good decoupling between channels was obtained and very high spatial resolution 3D images with a voxel size of 49 × 49 × 98 µm 3 were achieved in 1h22min scan time. Acquisitions allowed the quantification of cartilage morphological parameters such as thickness and volum

    A dedicated two-channel phased-array receiver coil for high-resolution MRI of the rat knee cartilage at 7 T

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    International audienceIn the field of small animal studies, the array coil imaging has become increasingly important. In this paper, a dedicated two-channel array coil operating at 300 MHz (7 T) for high-resolution MRI (HR-MRI) of the rat knee cartilage is presented. The average gain in signal-to-noise ratio (SNR) compared to a 15-mm multipurpose surface coil was 2.2. This SNR gain was used to improve the spatial resolution of 3-D acquisitions by decreasing the voxel size from 59 x 59 x 156 microm(3) to 51 x 51 x 94 microm(3) without time penalty. Also, a set of two array coils was used to perform a simultaneous acquisition of both knee joints of a rat, maintaining the same scanning time without SNR or spatial resolution degradation compared to the single knee joint acquisition. This two-channel array coil is a key element to perform HR-MRI and extract cartilage morphological parameters such as thickness and volume

    Age-related quantitative MRI changes in healthy cartilage: preliminary results.

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    International audienceOBJECTIVES: As the early form of OA is characterized by elevated water content in the cartilage tissue, the purpose of this study was to verify in vivo if age-related changes in patellar cartilage in healthy volunteers can be detected using quantitative MRI with T2 mapping and volume measurement MRI methods. DESIGN: Thirty healthy volunteers of various classes of age (18 to 65 years old) were enrolled in this study. MR images of the patellar cartilage were acquired at 1.5T. Patellar cartilage volume and T2 maps were determined. RESULTS: Despite non-significance, there was a trend in reducing cartilage volume with ageing (r: -0.25). In contrast global T2 slightly increased with ageing (r: 0.46). BMI (r: 0.51) and bone volume (r: 0.69) are well correlated to cartilage volume. CONCLUSION. Age-related physiologic changes in the water content of patellar cartilage can be detected using MRI. The proposed T2-mapping method, coupled with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA
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