Members of the MPI group: Erica Mason, Clarissa Cooley, Larry Wald, Emiri Mandeville and Joe Mandeville. Photo by Caroline Magnain.
Functional MRI has proved a transformative technology, yielding previously unimaginable insights into the workings of the brain. But what if there were another approach, one with dramatically higher sensitivity, that could shed even more light on these mysteries? What might we learn then?
Larry Wald is aiming to find out.
In late 2017 Wald, the Director of the Magnetic Resonance Physics & Instrumentation Group in the Martinos Center, was awarded a grant through the National Institutes of Health’s BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) that will support design and construction of a magnetic particle imaging (MPI) scanner for imaging of the human brain. Once completed and validated, the technology will offer an exciting new means to study activity in the brain. Ultimately, it could replace fMRI as the premier functional neuroimaging tool.
Magnetic particle imaging is not entirely unlike magnetic resonance imaging. Introduced a little more than a decade ago, it uses many of the same principles and shares many of the same technologies as the latter imaging modality. MPI differs in one crucial way, though: It directly detects the magnetization of nanoparticles injected into the body, rather than relying on secondary effects of magnetic resonance relaxation times. Directly imaging the source of contrast like this is what allows for the vastly improved sensitivity.
Today there are maybe a dozen groups around the world pursuing development of MPI. The researchers in these groups have been focused on a variety of possible applications, including applications in oncology; cell tracking; and cardiovascular, gastrointestinal and lung imaging. Notably, though, with all of the activity surrounding MPI, the researchers have neglected one particular area of interest: that is, the brain.
Wald was struck by this. He watched the groups setting often lofty goals for the technology while studiously avoiding the application directly in front of them. “I thought, ‘Everyone is ignoring the easy stuff,’” he says. “If these magnetic particles stay in the blood, and if you then directly detect the particle concentration, you are detecting blood. We have lots of interesting stuff to do with a blood detector in the brain: functional brain imaging!”
Deciding to dig a little deeper, Wald in 2014 applied for and was awarded one of the first BRAIN Initiative grants by the National Institutes of Health. With the support of this grant, he and his group set to work assessing the potential of MPI, examining the barriers to its use for neuroimaging in humans and, through simulations, testing the performance of various MPI scanner designs. (An MGH Research Scholar Award, which Wald received the following year for the project “Magnetic Particle Imaging for Breast Cancer Screening and Monitoring,” afforded further opportunities to explore the potential of the technology.)
The results of the work were encouraging. Wald and colleagues concluded that a first-generation human-size MPI scanner could offer tenfold higher sensitivity than conventional functional MRI with similar spatial resolution, with the possibility of improvement with further development.
In the wake of the research, they knew that a human-size MPI scanner with the potential to revolutionize neuroimaging was in fact achievable. Now all that remained for them was to make it.
Building a bigger mousetrap
The opportunity to construct the scanner came in 2017, when Wald applied for and was awarded his second BRAIN Initiative grant. This grant will support the construction and validation of an MPI device for use in humans, as outlined during the earlier research. Wald knows there will be challenges to face. “There is currently no human MPI scanner,” he reminds us. “And there is a reason for this: It’s hard.” But he has no doubt that the team he has assembled—which also includes Clarissa Cooley, Ken Kwong, Emiri Mandeville, Joe Mandeville, Erica Mason and Wim Vanduffel—will be able to address them.
What sorts of challenges will they need to tackle? The greatest difficulties may lie in translating the technology for human-size imaging—scaling up the field generation and detection, for example. Wald also anticipates a variety of “industrial type” challenges in designing and building the scanner. Not least: figuring out how to keep a two-ton, water-cooled electromagnet spinning around the subject’s head.
If successful, the new scanner will open up a range of applications for MPI, both in the lab and otherwise.
“We are betting that it will be a valuable tool for neuroscience,” Wald says. “But also, in the clinic, it could monitor for hemorrhage or, with targeted agents, look for tumors. We are hoping to have a solid proof of principle for these at the end of our five-year grant.”