Calcium fluoride based multifunctional nanoparticles for multimodal imaging.

New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF2:(Tb3+,Gd3+) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5-10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd3+ ions on the surface, the NPs reduce the MR T1 relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg-1·s-1. Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL-1 was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF2:(Tb3+,Gd3+) NPs are suitable for medical imaging.

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

UNLABELLED: : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. SIGNIFICANCE: Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

Comparison of multiple quantitative MRI parameters for characterization of the goat cartilage in an ongoing osteoarthritis: dGEMRIC, T1ρ and sodium.

RATIONALE AND OBJECTIVES: Osteoarthritis (OA) is a degenerative joint disease leading to cartilage deterioration by loss of matrix, fibrillation, formation of fissures, and ultimately complete loss of the cartilage surface. Here, three magnetic resonance imaging (MRI) techniques, dGEMRIC (delayed Gadolinium enhanced MRI of cartilage; dG1=T1,post; dG2=1/T1,post-1/T1,pre), T1ρ,and sodium MRI, are compared in a preclinical in vivo study to evaluate the differences in their potential for cartilage characterization and to establish an examination protocol for a following clinical study. MATERIALS AND METHODS: OA was induced in 12 caprine knees (6 control, 6 therapy). Adipose derived stem cells were injected afterwards as a treatment. The animals were examined healthy, 3 and 16 weeks postoperatively with all three MRI methods. Using statistical analysis, the OA development and the degree of correlation between the different MRI methods were determined. RESULTS: A strong correlation was observed between the dGEMRIC indices dG1 and dG2 (r=-0.87) which differ only in considering or not considering the T1 baseline. Moderate correlations were found between T1ρ and dG1 (r=0.55), T1ρ and dG2 (r=0.47) and at last, sodium and dG1 (r=0.45). The correlations found in this study match to the biomarkers which the methods are sensitive to. CONCLUSION: Even though the goat cartilage is significantly thinner than the human cartilage and even more in a degenerated cartilage, all three methods were able to characterize the cartilage over the whole period of time during an ongoing OA. Due to measurement and post processing optimizations, as well as the correlations detected in this work, the overall measurement time in future goat studies can be minimized. Moreover, an examination protocol for characterizing the cartilage in a clinical study was established.

Dynamic MR imaging of a minipig's knee using a high-density multi-channel receive array and a movement device.

OBJECT: To construct an optimised, high-density receive array and a movement device to achieve dynamic imaging of the knee in orthopedic large animal models (e.g., minipigs) at 1.5 T. MATERIALS AND METHODS: A 13-channel RF receive array was constructed, and the crucial choice of the array element size (based on considerations like region of interest, geometry of the minipig's knee, achievable signal-to-noise ratio, applicability of parallel imaging, etc.) was determined using the Q factors of loops with different sizes. A special movement device was constructed to guide and produce a reproducible motion of the minipig's knee during acquisition. RESULTS: The constructed array was electrically characterised and the reproducibility of the cyclic motion was validated. Snapshots of dynamic in vivo images taken at a temporal resolution (308 ms) are presented. Some of the fine internal structures within the minipig's knee, like cruciate ligaments, are traced in the snapshots. CONCLUSION: This study is a step towards making dynamic imaging which can give additional information about joint injuries when static MRI is not able to give sufficient information, a routine clinical application. There, the combination of a high-density receive array and a movement device will be highly helpful in the diagnosis and therapy monitoring of knee injuries in the future.