Check out our latest lay summary of a recent STARSTEM publication, Ultra Short Echo Time MRI of Iron-Labelled Mesenchymal Stem Cells in an Ovine Osteochondral Defect Model.

Dr Joshua Kaggie, Dr Frances Henson and team members from the University of Cambridge recently had this open access journal article published in Scientific Reports. Scientific Reports is an open-access journal publishing original research from across all areas of the natural sciences, medicine and engineering.

We asked the team to discuss their work.

What were you aiming to find out in this publication?

We would like to be able to image knee joints better, especially in the presence of stem cells labelled with iron oxides. Iron oxides cause rapid drop off in MRI signals, which can be compensated for by using a method called ‘ultra short echo time’ imaging to capture these signals.

 

Why is this important?

The use of stem cells is becoming increasingly studied, although we do not completely understand where these cells go and their effects on the joint. In order to ensure safe usage of the cells and push the technology, we need to understand how they interact inside live tissues, and thus, track them. To track these cells, they were labelled with iron-oxide particles or SPIONs – ‘super paramagnetic iron oxides’ – affect the magnetism in magnetic resonance imaging and cause rapid signal decays wherever the cells are concentrated. This imaging/tracking method allows us to confirm where the cells are located.

Interestingly, many models of osteoarthritis repair that work in mice do not work so well in larger animals, including sheep. Verification of osteoarthritic stem cell technologies in sheep is important in order to demonstrate safety prior to human trials.

 

Describe the methods chosen.

In this work, we use an MRI method, ‘ultra-short echo time imaging’ or UTE-MRI, captures the rapidly decaying MRI signals caused by these super-paramagnetic iron oxides and in hard-tissues like bone, to enable better measurements.

One of the fascinating aspects of UTE-MRI is that it uses a non-standard sampling pattern. In MRI, you can imagine that you sample the data like listening to a piano. You hit a key on the piano keyboard and listen. MRI is very similar to this, except this occurs with radiofrequencies rather than audible tones, but the principle is the same. You can sample the keyboard pattern one key at a time, up the musical scales one key at a time. This work alters the sampling pattern by collecting the signals earlier and uses a non-grid-like approach. It then also relies on advanced mathematics for image reconstruction beyond the typical MRI, called ‘non-linear Fourier transformations’.

This work imaged seven sheep stifles (or knees, except in sheep) with an osteoarthritis model, which was holes in their bone at the cartilage surface. We imaged their stifles with UTE-MRI and performed histology to confirm the presence SPIONs and to visualise how closely the histology matched the UTE-MRI data.

These two photos show cartilage and bone in a sheep that had an ‘osteochondral defect’, or hole in its bone. These images are an MRI (A) and histological sample imaged with a microscope (B). This MRI technique captures rapidly decaying MRI signals, thus called ‘ultra-short echo time imaging’.

 

How could this work benefit patients?

We were surprised in that the cells did not end up in the intended location, as we confirmed with histology and MRI. It was previously believed that stem cells honed to the site of the defect (or hole in the bone) in order to repair the tissue. This did not happen, which allows us to consider more interesting models, such as whether the cells recruit other cells to perform the repair.

If we can understand the mechanisms of repair, then we can target these mechanisms more accurately. By using more advanced imaging techniques, it allows us to visualise more clearly where the cells go into a large body system with a lot of different tissues.

We also hope that improvements on UTE-MRI can help in human imaging and diagnosis of bone/cartilage defects.

 

Who were your collaborators?

This work was done in collaboration with GE Healthcare.

 

What are the next steps?

This study leads into the follow-on study of using both MRI and photoacoustic imaging, and labelling the stem cells with MRI and photoacoustic agents, to confirm where the cells become located after injection and their effects on the repair of the tissue.

Our current work is on combining the use of iron-oxides and nanostars for imaging stem cells with two methods – magnetic resonance and photoacoustic imaging.

 

You can read the full paper online or download a PDF of the paper on our publications page.