Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Martinez Vera, N.
Tracking of magnetite labeled nanoparticles in the rat brain using MRI
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2017. pp. [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Ropele Stefan
Schmidt Reinhold
Stollberger Rudolf

To date, there are no effective treatments to relieve the burden of Alzheimer's disease, which causes cognitive impairment and memory loss for patients. Present pharmaceuticals do not penetrate the blood-brain barrier well and therefore are not useful for immediate treatment approaches. Among different strategies to overcome this barrier, nanoparticles are a promising tool to enhance targeted brain drug delivery. In this thesis, nanoparticles for drug transport in the healthy rat brain were traced with a clinical magnetic resonance imaging (MRI) scanner. In this work, relaxation time mapping and susceptibility weighted MRI were performed on a 3 Tesla system. To trace nanoparticles phantom studies were performed to assess the T1 and T2 relaxation time constants of magnetically labeled nanoparticle (MLNP) formulations based on biodegradable human serum albumin. In vivo MRI in mice and rats studied the effect and dynamics of MLNP uptake. In the brain, T1 changes induced by MLNPs were quantitatively assessed by T1 relaxation time mapping in vivo and compared to post-mortem results from fluorescence imaging. Rapid T1 mapping in vivo was performed using an optimized DESPOT1-sequence, which also provided susceptibility weighted imaging contrast by a combination of magnitude and phase images. Following its intravenous injection, MLNP uptake was seen in the rat liver and spleen, while no focal effect was detectable in the brain. However, histogram analysis of T1 and susceptibility changes in the brain demonstrated a diffuse presence of MLNPs, which also scaled with post-mortem fluorescence intensity. In addition, the absolute concentration of magnetite in the brain after MLNP injection by utilizing the susceptibility shifting effect of magnetite was determined, which was also confirmed by post-mortem fluorescence intensity. The novel approaches used in this thesis demonstrate the feasibility of tracking small concentrations of magnetite labeled nanoparticles in the brain of living rodents. These methods could support further research and development of drug loaded nanoparticles in Alzheimer's disease and other disorders of the brain.

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