A recent research paper in the journal Medical Physics sheds new light on the use of non-invasive magnetic particle spectroscopy to evaluate blood clots associated with a number of different diseases – ranging from stroke to myocardial infarction to deep vein thrombosis – holding out the promise of significantly earlier and more accurate diagnosis.  So, how exactly does magnetic particle spectroscopy work?  How can it be used it to assess blood clots?  And how might this approach be implemented in clinical settings?

The paper describes an investigation into how magnetic spectroscopy of nanoparticle Brownian rotation, a type of magnetic particle spectroscopy that’s particularly sensitive to the Brownian rotation of magnetic nanoparticles, was used to detect and characterize blood clots (Med. Phys. 10.1002/mp.12983).

As co-author John Weaver, professor of radiology at the Dartmouth‐Hitchcock Medical Center, explains, nanoparticle spectroscopy is used to measure the magnetization produced by magnetic nanoparticles in an alternating magnetic field – with an in-depth knowledge of the spectrum allowing users to measure “how free the nanoparticles are to follow the magnetic field”.

“Bound nanoparticles are less free than unbound nanoparticles, so we used spectroscopy to measure the number of bound nanoparticles,” Weaver explains. “If the nanoparticles are coated with antibodies, you can measure the molecular concentration of the molecule the antibody binds.”

The ties that bind

As part of their experiments, the research team coated magnetic nanoparticles with molecules that bind thrombin, the molecule that initiates the clotting process in blood.  Thrombin helps bind both cells and molecules in the initial stage of clotting.  New clots have a great deal of thrombin on their surface and, as the clots age, molecules of fibrin – an insoluble protein formed from fibrinogen during the blood clotting process, which forms a fibrous mesh to impede the flow of blood – become organized and clots present less surface thrombin.

“We reported an initial study where we measured the number of nanoparticles bound to the clot and how tightly they were bound.  In this preliminary study, we found that new clots have more nanoparticles bound to them and that the nanoparticles bound to the clots are more tightly bound,” says Weaver.

Put simply, this means that the “relaxation time” of the bound nanoparticles reduces as clots become more mature and organized. As such, the total number of nanoparticles that are capable of binding the clot gets lower and lower as clots age.  This discovery allowed the research team to confirm that the way nanoparticles interact with thrombin in clot formation differs over time.  On older clots, the nanoparticles bind the thrombin on the surface, whereas in clots still under development they bind a number of thrombin molecules or even become “trapped” in the clot matrix during formation.

At this stage, Weaver says that he and the rest of the research team are developing technology to evaluate the clot composition and structure in patients who are suffering acute ischemic stroke.  When clots have lodged in the large arteries supplying the brain, it is now becoming the standard of care to remove the clot with endovascular surgery.  However, he stresses that the success of this therapy may depend “on the nature of the clot, especially its mechanical stability”.

“The clinical application of nanoparticle spectroscopy will require the development of in vivo methods to deliver the nanoparticles, obtain sufficient signal from the nanoparticles on the clot and characterize the clot accurately,” Weaver adds.