RESEARCH

Contents:
MRI for investigating tissue engineering strategies
Quantitative MRI of microvascular physiology
Cellular MRI for non-invasive cell tracking and monitoring
Cellular MRI for early cancer detection and diagnosis
Rapid quantitative MRI

Magnetic resonance imaging (MRI) is a firmly established non-invasive 3D imaging modality that probes deep into the body and provides exquisite soft-tissue contrast at high spatial resolution for anatomical imaging. MRI can also provide information at the physiological, cellular, and molecular level, but a number of issues remain in this realm related to sensitivity, specificity, and quantification. Our lab is focused on developing reliable and robust quantitative MRI capabilities for physiological, cellular, and molecular imaging, with the aim of enabling MRI for advanced diagnostic and therapeutic applications. Our current focus is on applications in tissue engineering and regenerative medicine, cancer, and cardiovascular disease.
Currently our lab is exploring new ways to obtain information on important biological and biophysical parameters not currently accessible using non-invasive methods. Some examples include whether injected stem cells survive and develop into new tissue, how implanted scaffolds aid in regeneration, if a cancer cell is very aggressive, and if the tiny blood vessels that nourish our tissue are dysfunctional. Answers to these questions will enable better diagnostics and guide the development of effective treatments. Our research endeavours sit at the interface of multiple disciplines and require MRI physics development alongside working with new chemical agents for contrast-enhanced imaging, cell biology, animal models of disease, and mathematical/engineering concepts applied to solve biomedical problems. Specific areas of research include:

MRI for investigating tissue engineering strategies
This broad research program aims to advance the capabilities of non-invasive MRI for enabling critical advances in tissue engineering and regenerative medicine. Specific focus is given to developing MRI to provide physiological, cellular, and molecular information to investigate and optimize difficult tissue-engineering problems such as angiogenesis and cell-based therapy. While new MRI techniques are being specifically developed to optimize tissue-engineering approaches, some MRI techniques employed here will be translated directly from other applications, as described in the following.

Quantitative MRI of microvascular physiology
The microvasculature, or the nutritive blood vessels in our body, is essential to maintaining tissue health. Loss of proper microvascular function underlies a wide range of conditions, including cancer, stroke, and cardiovascular disease. This is why being able to evaluate the health of these small blood vessels is important for diagnosis and assessment of treatment effect. Yet, despite the ability of current advanced technologies to probe microvascular function, such as blood flow, in a non-invasive manner, it remains very difficult to detect the early signs of microvessel dysfunction. In this research program, we are developing new non-invasive imaging methods based on MRI to find those early changes sooner than we can today, in the hope that early detection will enable early intervention for improved outcome.

Cellular MRI for non-invasive cell tracking and monitoring
The ability to see cells inside a living body can transform how we detect and diagnose disease and monitor treatment. From differentiating healthy from unhealthy cells, to tracking therapeutic cells that are injected into the body, cellular imaging is an active biomedical research area. Yet, when we think of cellular imaging, we usually think of looking at samples under a microscope. This research program strives to develop a similar capability to look at cells but using MRI for non-invasive, deep-tissue penetration in a living subject. Our goal is to improve detection sensitivity and specificity to make MRI the technology of choice for non-invasive human cellular imaging.

Cellular MRI for early cancer detection and diagnosis
We were the first to show that early developing cancers that have not yet developed a significant blood supply, ones that are missed on conventional clinical MRI, can be detected using a cellular imaging approach. This is important, as metastasis often occurs in the early stages before the primary tumor becomes large enough to be detected. The ability to see cancer cells, when they are still low in number, is critical to finding cancers early, whether they are primary or metastatic tumors, and treating them when curable options may still be available. We are currently finding more sensitive methods to detect even smaller cancers and to determine their potential for metastasis.

Rapid quantitative MRI
This broad program encompasses both rapid image acquisition and near real-time data analysis. Unlike conventional clinical MRI scans, quantitative imaging entails a much lengthier acquisition time and the collection of very large datasets to tease out quantitative biophysical entities and underlying biological parameters, such as blood perfusion. Our lab has developed a number of rapid high-resolution 3D acquisition approaches for quantitative imaging. We continue to investigate more rapid acquisition methods through sparser sampling of the acquisition data space, as well as implement parallel data processing to greatly accelerate the analysis of large 3D and 4D MRI datasets.