Stroke is one of the leading causes of death and disability worldwide. Time is of the essence for successful diagnosis and treatment of stroke patients given the fact that two million neurons die every minute after the onset of a stroke.

Monitoring blood flow in brain vessels is one of the best ways to diagnose stroke but brain imaging today mainly relies on techniques like X-ray computed tomography and magnetic resonance angiography. Although these methods are non-invasive and efficient, they cannot image structures several microns in size and are also slow.

SPIO nanoparticles

MPI was invented at the beginning of this century and provides fast, background-free, sensitive, directly quantifiable, 4D information on how superparamagnetic iron oxide (SPIO) nanoparticles are distributed. It is the first biomedical imaging technique that truly depends on the physical properties of a nanoscale material – in this case, the way the SPIOs relax after being subject to alternating magnetic fields. The technique exploits the fact that magnetic nanoparticles relax faster in a finite magnetic field than in no field at all and researchers directly obtain an image of the magnetic nanoparticle tracers by mapping how their magnetism decays.

Thanks to its high spatial resolution, the technique can be used to obtain images of blood flow in brain vessels in real time, but until now this has never been proven in an in vivo experiment because of the lack of MPI scanners that are sensitive enough at high temporal resolution.

Mice with cerebral ischemia

A team of researchers led by Tim Magnus of the University Medical Center Hamburg-Eppendorf in Germany worked with a preclinical MPI scanner developed by Philips Medizin System and manufactured by Bruker. This machine relies on a so-called field free point (FFP) for spatial encoding and works at different frequencies of around 25 kHz and a magnetic field strength of up to 14 mT.

Magnus and colleagues studied mice with cerebral ischemia (induced by inserting a microfilament in the internal carotid artery of the animals, which blocks blood flow into the medial cerebral artery). After injecting the SPIOs, the researchers imaged the mice brain blood vessels with MPI and found that the imaging signal decreased in the ischemic hemisphere because of blood flow deficits in this region. This observation allowed them to precisely detect an ischemic stroke of a few mm3 in size, which is the same as they were able to with a 7T small animal MRI scanner but in real time.

Portable MPI scanners on stroke or intensive care units

Although there are still many hurdles to overcome before MPI can become a stand-alone imaging technique for stroke patients, it does show promise, say the researchers. “The technology behind MPI allows the construction of portable MPI scanners,” they write in their paper, published in ACS Nano DOI: 10.1021/acsnano.7b05784, “and the first prototypes of such small, single-sided mobile MPI scanners have already been developed.”

"The most realistic application will be continuous monitoring of cerebral perfusion in patients with stroke, bleeding and subarachnoid hemorrhage," team member and lead author of the study Peter Ludewig tells nanotechweb.org. "At the moment, there is no technique for continuous monitoring, just clinical examinations every three hours, so a deterioration in the patient's health between these examinations can be missed."

The researchers say that they will also have to make sure that the SPIO nanoparticles are not toxic over the long term. That said they do state that: “Resovist, which is a clinically approved SPIO contrast agent, has already been used in humans with a similar safety profile, as compared to MRI contrast agents, and can even be applied in patients with renal failure”.