Sep 29, 2011
Gadolinium oxide nanoparticles enhance MRI contrast
Ultra-small gadolinium oxide nanoparticles (Gd2O3) are being developed as positive contrast agents for molecular and cellular magnetic resonance imaging (MRI). Recent studies have demonstrated that these particles can be used to label and track cells in vivo. Positive contrast agents enhance the signal, which results in a local "brightening" in MRI scans. These agents could represent an attractive tool for examining cell diffusion processes. However, once internalized into cells, nanoparticles tend to agglomerate in cell endosomes. But how much aggregation takes place? And how does this affect the performance of Gd2O3 nanoparticles in MRI cell tracking studies?
To answer these questions, Canadian and Belgian researchers have conducted a series of investigations. The researchers: Marc-André Fortin and Luc Faucher from Université Laval, Québec, Canada, reported earlier this year on the use of US-Gd2O3 particles for "positively contrasted" cellular imaging, and were joined by Yves Gossuin from Université de Mons, Belgium.
Gadolinium (Gd) is a paramagnetic element widely used in MRI. However, most gadolinium complexes used nowadays are not suitable for molecular and cellular imaging because of the relatively weak unitary impact of each one of the gadolinium atoms on the relaxation time of hydrogen protons (providing the "signal" detected in MRI). To enhance the detectability of Gd-based contrast agents, one strategy is to bring hundreds of Gd atoms into so-called "ultra-small nanoparticles". Adequately coated, such particles are very efficiently ingested by cells and are considered as promising "probes" for cell tracking in MRI.
Field strength assessment
The team recently measured the efficiency of Gd2O3 suspensions for MRI applications (longitudinal and transverse relaxivities). Data acquired at magnetic field strengths typical of most hospital scanners (0.5–3 T), were compared with measurements at higher magnetic field strengths (7–11.7 T) as found in MRI systems mainly used in pre-clinical research.
At every magnetic field, the longitudinal relaxivity (r1) decreased upon agglomeration, while remaining high enough to provide positive contrast. The transverse relaxivity (r2) decreased slightly at 0.47 and 1.41 T, which is good for clinical MRI; however, it was enhanced at higher fields (7 and 11.7 T) upon agglomeration, thereby affecting the positive contrast enhancement effect. This is due to the total magnetic moment developed during agglomeration, since paramagnetic aggregates are considered as large magnetized spheres.
Given that agglomeration is susceptible to occur once particles are ingested in the cells, this is a significant finding to clearly establish the magnetic field strengths at which US-Gd2O3 particles might be preferentially used.
The researchers suggest the development of highly hydrated nanoparticle coatings to maintain the interaction of surface gadolinium with 1H protons in spite of aggregation. Modulating the thickness of the nanoparticle polymer coating would also help to prevent the decrease of transversal relaxation time at high magnetic fields, which is caused by the close proximity of Gd2O3 nanocrystals upon agglomeration.
The study clearly establishes the potential of ultra-small Gd2O3 nanoparticles as a "positive" contrast agent for MRI, which is particularly efficient and potentially very useful at clinical magnetic field strengths (1–3 T).
More information can be found in the journal Nanotechnology.
About the author
Luc Faucher is a PhD student at the Laboratoire de Biomatériaux pour l'Imagerie Médicale (BIM, Université Laval, Canada). The research group is directed by Dr Marc-André Fortin and focuses on the development of new biomaterials for imaging applications. Dr Fortin is professor at Université Laval's department of Engineering Materials and is also affiliated to the CHUQ research center. His main interests are the development of contrast agents for cell labelling, cytotoxic studies and imaging of biomaterials. Dr Yves Gossuin is assistant in chief at the Service de Physique Expérimentale et Biologique (Université de Mons, Belgium). Dr Gossuin is an expert in the theoretical aspects of contrast agents, and was assisted by PhD student Aline Hocq.