The NMR Center has a strong program in developing techniques for cellular and molecular imaging, non-invasively, by MRI. The research programs involve the development of novel contrast agents and cell labeling techniques that can be used to 'tag' different cell types and the development new MRI image acquisition and signal processing techniques for detecting and quantifying labeled cells in vivo.

The ability to track and identify cell populations non-invasively by MRI has profound implications in basic sciences and medicine. With these tools, the biomedical research community will have the ability to probe the discrete mechanisms of diseases and investigate the efficacy of novel therapies, as well as, clinically monitor the therapeutic treatments in patients.

We currently have active programs developing and investigating the properties of novel cellular contrast agents based on super-paramagnetic iron oxide, gadolinium chelates, and fluorine compounds.

Examples of research:

Tracking immune cell infiltration in a model of acute cardiac transplant rejection

The above images show short-axis cardiac-gated MRI images of donor hearts that are transplanted into the abdomen of the recipient rat as a model for acute cardiac transplant rejection. (Labels, RV:right ventricle, LV:left ventricle) This is a working heart transplantation model where the heart beat and circulation are similar to those of the native heart. Images A and C show allograft hearts undergoing Grade 3 rejection. Image B is an isograft control (no immunological rejection occurs). By using different iron-oxide based cellular contrast agents, different contrast patterns are observed as labeled macrophages infiltrate the heart. In image A, the immune cells are labeled with micron-sized iron oxide (MPIO) particles, and individual contrast agent labeled cells are observed as punctate dark spots. In Image C, the immune cells are labeled with nano-sized iron oxide particels (USPIO), and large areas of dark contrast are observed. In the isograft control, Image C, no labeled immune cells are observed infiltrating the transplanted heart. This model of organ rejection and the contrast agent and imaging technologies being developed will allow us to better understand the mechanism of organ rejection and potentially lead to improved clinical method to detetect organ rejection, non-invasively, by MRI.

Tracking cells by Fluorine MRI

We have developed a cell labeling and imaging platform based on labeling cells with perfluoropolyether (PFPE) nanoparticles. Cells can be labeled with the PFPE nanoparticles, and 19-F MRI is selective for only the labeled cells. A conventional MRI can then be used to place the labeled cells in their corresponding anatomical context. Furthermore, the PFPE nanoparticles can be used to efficiently label many different cell types. In the example shown above, dendritic cells (DCs) were labeled and the labeled cells injected into a mouse. The image of the labeled cells (19-F images) are displayed in a "hot-iron" intensity scale, and the anatomical images are shown in grayscale. The three panels on the far left (image a) are of a mouse quadricep after intramuscular injection of DCs (asterisk indicates injection site) The 19-F and 1-H images (from left to right) and a "composite" 19-F/1-H image. Image b shows a composite image of DC migration into the popliteal lymph node following a hind foot pad injection. And image c shows a composite image through the torso following intravenous inoculation with labeled DCs. Cells are apparent in the liver (L), spleen (S), and weakly in the lungs (Lu). This new cellular imaging platform will provide the tools necessary to better underdstand the celluar mechanisms of diseases, develop new therapeutic treatments, and assist in translating these therapies from the bench to the bedside.

Recent publications in molecular and cellular imaging:

Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. more

MRI detection of macrophages labeled using micrometer-sized iron oxide particles. more

Theoretical MRI contrast model for exogenous T2 agents. more

In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. more

Immune Cells Detection of the In Vivo Rejecting Heart in USPIO-Enhanced Magnetic Resonance Imaging. more

Non-Invasive Detection and Staging of Cardiac Transplant Rejection. more

In vivo imaging platform for tracking immunotherapeutic cells. more

A new transgene reporter for in vivo magnetic resonance imaging. more