Iron Oxide Nanoparticles Imaging Tracking by MR Advanced Techniques: Dual-Contrast Approaches (2012)

Recently a number of imaging modalities have been presented for cellular imaging including magnetic resonance imaging (MRI), optical imaging, and positron emission tomography (PET) based on the background of growing demand for molecular imaging to noninvasively and longitudinally visualize cell migration and track transplanted cells in vivo, also to monitor cell biodistribution.Cellular MRI, with its superb ability of resolving soft tissue anatomies in three-dimensions (3D) with high spatial resolution in comparison to other modalities, is particularly important as a noninvasive tool to provide unique information on the dynamics of cell migration in vivo (Modo, 2005; Arbab, 2008a;Zhang, 2008).In vivo MRI of cells is very useful for studying tumors, inflammation, stem cell therapy, and immune response, etc.Cells labeled with commercially available iron oxide nanoparticles (iron particles) can be imaged for weeks with MRI.The labeling procedure does not exhibit any alteration to cell viability or function (Bulte, 2004;Oude Engberink, 2007).Superparamagnetic iron oxides (SPIO) and ultra-small superparamagnetic iron oxide (USPIO) particles are commercial MR contrast agents for cell labeling due to their biocompatibility and strong effects upon T 2 and T 2 * relaxation.Several labeling methods have been developed to incorporate sufficient quantities of iron into cells.Cellular MRI has now been widely used for tracking transplanted iron-labeled therapeutic cells in vivo (Bulte, 2004;Oude Engberink, 2007).The technique has recently been introduced into the clinic (de Vries, 2005).The effect from iron particles is seen as hypointensity or negative-contrast on T 2 -and T 2 *-weighted images because of the shortening of T 2 and T 2 * relaxation times.However, concerns have been raised that the negative-contrast could be non-specific and difficult to differentiate from signal hypo-intensities resulting from susceptibility artifacts (i.e. from the presence of air or other field inhomogeneities), flow related signal losses, and calcification.Therefore, several positive-contrast and even dual-contrast imaging techniques have recently been developed for tracking iron-labeled cells.Dual-contrast imaging effectively permits detection of the presence of iron-labeled cells with both negative-and positive-contrast within a single image.This chapter illustrates negative-and positivecontrast MR techniques for tracking iron-labeled cells.Particular attention was paid to www.intechopen.comSmart Nanoparticles Technology 150 recently developed positive-contrast cell tracking techniques, the status of dual-contrast approaches of new MRI pulse sequences and image postprocessing techniques and their perspectives.The new advanced technology in imaging contrast of iron oxide NPs on multimodal platform will also be introduced. Negative-contrast MRI techniquesCellular MRI is a newly emerging field of MR research that allows the "non-invasive, quantitative, and repetitive imaging of targeted macromolecules and biological processes in living organisms" (Herschman, 2003).Cellular MRI requires that cells are labeled with MR contrast agent to make them distinct from the surrounding tissues.Iron oxide nanoparticles are regarded as the most extensively applied contrast agent in cell imaging and cell tracking studies based on the fact of their strong negative contrast effect, biocompatibility, variety in core size and coating surface, as well as ease of detection at microscopic level (Muja, 2009).SPIO and USPIO are currently the predominant MRI contrast agents.The description of the physical and chemical properties of SPIO and USPIO can be found in recent reviews (Herschman, 2003;Thorek, 2006;Muja, 2009).The sizes of monocrystalline iron oxide nanoparticles (MIONs) ≈ 3 nm in diameter, USPIO particles ≈ 15-30 nm, SPIO particles ≈ 60-180 nm and micron sized iron oxide particles (MPIOs) can be as large as 10 μm (Shapiro, 2005).Some of the SPIO and USPIO agents, such as Endorem (SPIO, Guebert), Ferumoxides (SPIO, Berlex) and Resovist (USPIO, Schering), are already approved by the Food and Drug Administration (FDA) and are extensively used for imaging of the liver, central nervous system (CNS) and lymphatic system (Arbab, 2004b; Helmberger, 2005;Manninger, 2005), etc. Cationic transfection agents such as poly-L-lysine or the FDA-approved protamine sulfate are used to increase labeling efficiency in vitro.SPIO particles may decrease T 2 * by magnetic susceptibility effect and T 2 by dipole-dipole interaction or scalar effect between protons and magnetic centre.A large magnetisation difference occurs as a result of the nonhomogeneous distribution of superparamagnetic particles, which gives rise to local field gradients that accelerate the loss of phase coherence of the spins contributing to the MR signal.Iron-labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell such that iron-labeled cells were visualized as signal voids on T 2 and T 2 * weighted images (negative-contrast MR imaging).Negative-contrast techniques are the most commonly used approach for the detection of the SPIO-labeled cells.While cell-based therapies have attracted well attention as novel therapeutics for the treatment of so many kinds of diseases, investigations (Zhang, 2005;Heyn, 2005Heyn, , 2006) ) have showed that single, living, highly phagocytic large cells, such as macrophages, or human endothelial cells can be tracked over time in MRI using a 3.0 T even 1.5 T scanner.As an example of stem cell-based studies, investigators (Anderson, 2005) demonstrated that MRI of iron-labeled stem cells was directly identified in neovasculature of a glioma model.The cells were labeled using the ferumoxides/poly-L-lysine complex in vitro and the labeled cells were then injected in the model, and their migration toward and incorporation into the tumor neovasculature was visualized in vivo with negative-contrast MRI.Other studies have shown that ferumoxides-TA labeled human MSCs will home to liver (Arbab, 2004a), tumors (Khakoo, 2006), or heart (Kraitchman, 2005), illustrated at negative-contrast imaging with MR scan and confirmed at histologic evaluation.A group (Zhu, 2006) labeled neural www.intechopen.com