This lecture will discuss the use of iron based contrast agents for cellular and molecular MRI. The mechanisms of contrast, detection limits, limitations and advances will be described.
Cell Tracking and Molecular Contrast
To detect cells using MRI they must be labeled with MR contrast material to make them distinct from the surrounding tissues. Most cell tracking studies utilize iron oxide based nanoparticles as contrast agents to label cells. The presence of iron within cells generates a large magnetic moment which causes disturbances in the local magnetic field (inhomogeneities). This leads to rapid dephasing, faster T2 and T2* relaxation, resulting in signal intensity loss. Areas containing iron-labeled cells therefore appear as regions of signal void, or signal hypointensity, in MR images, creating negative contrast (1). The susceptibility induced signal loss is more substantial for T2*-weighted GRE images and the size of the region of signal loss is influenced by the amount of iron, the echo time and the magnetic field strength (2).
A variety of iron oxide-based labels are available including superparamagnetic iron oxide particles (SPIO, 60-120nm), ultra-small iron oxide agents (USPIO, 10-30nm) and micron-sized iron oxide particles (MPIO, 0.75 mm and larger). This lecture will describe the various contrast agents currently commercially available for preclinical investigations in animals and the possibilities for clinical cell tracking. In experimental cellular MRI, there are two main approaches for labeling cells with iron particles (i) cells are loaded with magnetic particles prior to their injection or implantation and (ii) iron particles are administered intravenously resulting in labeling of cells in situ (3). The resulting signal hypo-intensities in MR images can be tracked in vivo providing information about the presence, location and migration of the iron-labeled cells.
An understanding of the current limitations of cell tracking with iron particles is important to our understanding of what advances and improvements are crucial to move this field forward. These will be discussed and include: the potential for transfer of label from the original cell to bystander cells, dilution of the label in proliferating cells, misinterpretation of the signal from iron-labeled cells due to other sources of signal loss and quantification of signal loss in MR images (3).
This lecture will also cover advances in the field related to both the cell labeling and the MRI hardware and software for detection of cells. Some of the advances in the field of preclinical tracking with iron-based labels include: improved methods for labeling cells, novel iron agents, and other contrast agents. Finally, developments in MRI hardware and pulse sequence technology which aim to push the limits of detection of labeled cells will be described and the limits of cellular detection with MRI will be compared/contrasted with that of other micro-imaging modalities.
1. Heyn et al. In vivo MRI of single cells in mouse brain with optical validation. Magn Reson Med. 2006 Jan;55(1):23-9.
2. Shapiro et al. In vivo detection of single cells by MRI. Magn Reson Med. 2006 Feb;55(2):242-9.
3. Makela et al. Cellular Imaging with MRI. Top Magn Reson Imaging. 2016 Oct;25(5):177-186