Researchers at the Hebrew University of Jerusalem, Tel Aviv Sourasky Medical Center and Shaare Zedek Medical Center have developed new magnetic resonance imaging (MRI) technology that noninvasively assesses iron levels in living human brains. The breakthrough sheds light on iron’s critical role in brain function, aging, and diseases like cancer, Alzheimer’s and Parkinson’s.
Iron is an important mineral for brain function. It is essential for energy in the brain, the building of the myelin sheath that insulates nerves, and repairing damaged tissue. Iron molecules are delivered to the brain by blood. The iron binds to proteins that either bring it to the brain cells or store it for later.
However, iron in the brain that does not bind to proteins can be dangerous and toxic and even lead to death.
“That’s why we need to maintain a very delicate balance of iron in the brain,” said Shir Filo, the lead author of the paper about the new MRI technology published in the peer-reviewed Nature Communications journal.
Filo is a PhD candidate in the computational neuroscience program at the Edmond and Lily Safra Center for Brain Sciences at Hebrew University. She is a member of Prof. Aviv Mezer’s lab, which is focused on in vivo mapping of human brain structures, mainly using MRI.
Filo told The Times of Israel that before the advent of this new technology, there was no way to measure the iron balance in a living brain. It was only possible to do so on postmortem brains or tumor tissue removed by surgery and sent to a pathologist for study.
“What we wanted to do was develop a quantitative means of measuring iron in a living brain, and we figured out how to do this using MRI scans,” Filo said.
The approach requires nothing more advanced than a standard MRI machine that one would find in a hospital or radiology clinic. The key was finding a way to “turn the MRI into less of a camera and more into a scientific measuring device,” as Filo put it.
She likened the usual images produced by an MRI scanner and interpreted by a trained physician’s eye to a person putting a hand on the forehead of someone who may be running a fever. Looking at the scans provides some information about possible problems with brain iron levels, just as a hand on the forehead indicates that the sick person feels hot.
“The technology that we have developed turns MRI scans into a thermometer, which lets you know exactly how many degrees above normal a person’s temperature is,” Filo explained, completing the metaphor.
Filo and her fellow researchers turned to physics — the language of the MRI — to measure a biological process within the brain. They combined different scans and applied physical calculations and models to them.
“We noticed that each of these scans is sensitive to a different kind of feature of the iron, and so when we combine them in a physical model that describes the way the MRI signal is sensitive to the effects of iron, we could produce measurements that are quantitative about the iron balance in the brain,” Filo said.
Filo and the others involved in this study are not the only researchers around the world looking into the use of quantitative MRI to better understand the brain. However, this study is unique in that part of it involved scanning 18 patients with brain tumors before they underwent surgery to determine iron levels. Those quantitative assessments were compared to others completed by pathologists on the same tissues after their removal.
“You don’t usually get to compare the same exact tissue. Usually, you have to compare what you calculated from the MRIs to some information from the literature or a postmortem. Here we actually had live tissue scans and get to test our approach this way — and we got really encouraging results,” Filo said.
In another part of the research, the team scanned the brains of 40 healthy patients, with a focus on the varying iron balances in different parts of the brain, each with their unique function. The scientists compared their findings to those in the literature and found a close correspondence.
“We had older and younger subjects in that part of the study, so we were able to study aging with this,” Filo noted.
Before the researchers even started studying the brain MRIs of healthy and sick individuals, they worked with synthetic samples imitating brain tissue. This way, they could control the iron balance in each of the various brain centers and make sure that their technique was sensitive to the differences.
Filo cautioned that the study’s positive results do not mean that this novel approach will immediately be applied in clinical settings. There is still a lot more to be done with the technique in the lab to better understand processes that occur in the brain.
But with this new ability to measure iron balances, Filo said she and her colleagues believe that they will soon be able to better understand the aging process and what happens in the brains of people with Alzheimer’s, Parkinson’s and other neurodegenerative diseases.
“We also hope our technology will provide doctors with information on the molecular specification of brain tumors before they operate on their patients. They will be able to make more informed decisions on how to operate, how urgently to operate, and perhaps be able to decide not to operate at all,” Filo said.