It’s practically endemic in the modern world. The college student finishing a term paper as the sun comes up, the new parents feeding the baby at 3 a.m., the foreman on the graveyard shift — they’re all among the more than a third of adults in the U.S. who don’t get enough sleep. Long-term, sleep deprivation can have severe ramifications, beyond what can be remedied by a double espresso or a power nap. In fact, recent research indicates that regularly getting less than seven hours of sleep per night can raise your risk of developing dementia later in life by nearly a third.
This is of particular concern in the military, because only 30% of active-duty warfighters manage to sleep even six hours on average per night. To better understand the problem, the U.S. Department of Defense has awarded a $3.4 million grant to GE Research and the Uniformed Services University (USU), the U.S. government’s health sciences university, for a study that could yield new insights into the effects of sleep deprivation on human performance and brain health.
The team will use GE’s experimental, high-performance MRI system, MAGNUS — short for Microstructure Anatomy Gradient for Neuroimaging with Ultrafast Scanning. First unveiled in 2020, MAGNUS is a noninvasive brain-imaging platform that produces exquisitely detailed magnetic resonance imaging scans. “The clarity and quality of these images is unparalleled,” says Luca Marinelli, a senior principal scientist at GE Research, who is leading the study.
He and his colleagues at GE Research, in Niskayuna, New York, are working to advance the state of the art of MRI. Traditional MRIs use magnetic fields and electromagnetic radiofrequency waves to construct detailed pictures of structures inside the body. Patients typically lie inside a cylinder.
MAGNUS was designed specifically for brain imaging. It is a novel take on one of the key systems of an MRI scanner, the gradient coil, which has an inner diameter about the width of a large pizza. That’s just wide enough to fit a person’s head but not their shoulders — only the head of the subject goes inside the scanner, while most of the body is outside. The gradient coil is responsible for shaping the magnetic field inside the scanner bore to encode spatial position and image contrast. MAGNUS’s gradient coils are three times faster and more powerful than those in clinical MRI machines, to deliver images with high resolution and sensitivity to spatial structures such as axons and fine cortical features to a degree previously attainable only in postmortem or animal studies. The innovative asymmetric design of the MAGNUS gradient coil developed by the GE team, led by Thomas Foo, chief scientist in biology and applied physics, enabled this unprecedented performance in human brain imaging.
The GE researchers hope that boost in performance will help illuminate some of the brain’s inner workings and have started studying a biological pathway called the glymphatic system. Discovered a decade ago, this web of channels acts as a neurological showerhead, flushing out metabolic waste. “If you can clear that stuff out, you promote brain health by keeping the brain nice and tidy,” Marinelli says.
But if the cleansing process is disrupted, waste products may accumulate and cause damage. Researchers believe that disturbances to the glymphatic pathway could be linked to an increased risk of developing neurodegenerative illnesses such as Alzheimer’s disease. One possible disturbance is a lack of sleep. Experiments on animals and preclinical studies have shown that the flushing process is most active during deep sleep. This raises the question of whether disruptions to sleep — such as those experienced by 70% of active-duty warfighters — reduce the effectiveness of the clearing of waste from the brain, raising the likelihood of developing a neurodegenerative disease.
While supported by animal research, that hypothesis has proven difficult to test in humans. Cerebrospinal fluid (CSF), the watery liquid that rinses away toxic substances, moves very slowly through the glymphatic pathway — on the order of about 5 to 10 inches per hour. Previous attempts to depict glymphatic flow in humans have relied on invasive techniques to enhance visibility, such as the injection of heavy-metal-based contrast agents via spinal tap.
Now, with the DOD-funded study, MAGNUS could enable the first noninvasive in vivo measurements of the glymphatic pathway in humans. Because MAGNUS’s combination of gradient strength and speed allows it to sensitize data acquisition to the slow flow of CSF even without a contrast medium, GE and USU researchers hope to use it to map the glymphatic pathway over an entire sleep cycle. The study will include a mix of good sleepers and sleep-deprived subjects recruited by USU and will be led by co-principal investigator Lt. Cdr. Kent Werner.“The goal is to see if we can spot differences in the effectiveness and efficiency of glymphatic circulation in people who sleep well relative to people with sleep restriction,” Marinelli says.
MAGNUS is already being used in a study of traumatic brain injury in collaboration with USU researchers, and it promises to shed light on other poorly understood nervous system pathologies in the future. “To solve the most important problems in neurology, we need new tools,” Marinelli says. “MAGNUS is bringing image quality to brain scans that we’ve never seen before.”
The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office and this work was supported by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Defense Health Program, Congressionally Directed Medical Research Programs (CDMRP), Peer Reviewed Medical Research Program, Investigator-Initiated Research Award – Partnering PI (Principal Investigator) Option, in the amount of $2,509,233, under Award No. W81XWH2220038, and $910,559 under Award No. W81XWH-22-2-0037. MAGNUS also was developed under a separate CDMRP grant under Award No. W81XWH-16-2-0054 in the amount of $5,372,359. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense.
Image credit: iStock.