Development of Quantitative In Vivo Cellular and Molecular MR Imaging Techniques

The Problem

There are a number of important yet unanswered biological questions about how cells and molecules behave in the body, i.e. in vivo. Although researchers have discovered a large amount of information using cutting edge tools to map individual cells down to the genome, in many cases we still don't understand how overall cell populations actually interact and behave in the body. Several imaging techniques have been developed that allow monitoring of cells over time in vivo, but the techniques that offer the best quality images only result in qualitative information, limiting our observations.

There are no existing imaging technologies to provide non-invasive, quantitative information in the body that can be measured over long periods of time. Quantitative information is essential to allow us to evaluate subtle changes in how cells and molecules migrate to different areas around the body in response to various types of external distortions like diseases and drugs. This information will yield valuable insight into a variety of biological processes, particularly in the field of immunology, where there are a number of types of cells with very complex interactions, such as cancer.

The Solution

Magnetic resonance imaging (MRI) is an imaging technique well known for its ability to image a large variety of materials, from human tissue to concrete. It can also be used to track individual cells and molecules that have been labeled with a contrast agent. This program will develop and evaluate MRI-based quantitative measures of biological agents tagged with superparamagnetic iron oxide (SPIO).

For quantification of SPIO-labeled cells, the first part of my program will involve developing and evaluating an novel MRI method called TurboSPI. I will be working to increase imaging speed and quantitative accuracy of this technique to enable its use in biological systems, as it could give us important information on determining not only concentrations of iron, but cell number and total volume.

For the quantification of SPIO-labeled molecules such as peptides, I am proposing the development of a novel quantitative sequence based on an exciting new technique called magnetic resonance fingerprinting (MRF) combined with a method that has already been shown to have high sensitivity to SPIO-labeled cells. This technique will allow the generation of several MRI parameter maps, allowing accurate quantification of SPIO-labeled molecules, and potentially cells as well.

Impact

This program of research describes a coherent sequence of projects that will develop and validate novel tools for use in quantification of individual cells and molecules labeled with SPIO using MRI. This work will result in advanced imaging technologies that can be broadly applied in a number of biological fields and can improve our understanding of basic immunological behavior, particularly with respect to cancer therapies.