CHOP Researchers Pushing the Boundaries of Magnetic Resonance Imaging

Sodium MRI scan reveals a pediatric patient with a tumor centered in the brainstem after radiation treatment. Elevated signal in the tumor (in red) represents elevated sodium concentration in the tumor, which demands clinical attention.

Two magnetic resonance imaging (MRI) technologies under investigation at Children’s Hospital of Philadelphia Research Institute have the potential to redefine how doctors detect and treat a wide range of childhood diseases.

Direct sodium MRI is improving the detection and understanding of brain tumors, while delta wave MRI could offer new insights into brain function during traumatic injuries and psychiatric disorders.

Both noninvasive techniques do more than produce sharp images — they are helping clinicians pinpoint precisely how disease and injury affect the body on a granular level, said Timothy Roberts, PhD, Vice Chair of Research in the Department of Radiology and leader of the Program in Advanced Imaging Research (PAIR).

“These techniques have the potential to be transformational, and they’re the result of the multimodal environment at CHOP,” Dr. Roberts said. “PAIR is breaking the mold on interdisciplinary collaborations.”

Tracking Tumor Response in Real Time

When Aashim Bhatia, MD, joined CHOP’s Department of Radiology, he teamed up with Dr. Roberts, an imaging physicist; their combined expertise is advancing sodium MR neuroimaging, a largely uncharted but promising field of clinical research.

Conventional MRI uses a magnetic field that aligns hydrogen atoms in the body, since hydrogen is abundant in human tissue. The machine then sends radio waves to temporarily disrupt that alignment. When the hydrogen atoms return to their original state, they emit signals that the MRI machine detects to create detailed images of the body’s structures. Since tumors have different amounts of hydrogen than healthy tissue, they often appear brighter on a scan, allowing clinicians to track their growth and regression.

A shortfall of conventional MRI is that the effects of radiation and chemotherapy can cause signal changes and inflammation in the body that may look very similar to tumor growth. Radiologists are often unable to accurately detect whether the tumor is responding to treatment, or if the scan is simply showing post-treatment changes.

“Often a patient will be asked to come back in three months for another scan,” Dr. Bhatia said.

Sodium MRI, by contrast, uses sodium nuclei, rather than hydrogen nuclei in water molecules, to create images. While the concentration of sodium in normal cells is low, the ion is highly concentrated in tumor cells. This makes sodium MRI potentially more adept at distinguishing between active tumor and healthy tissue — or post-treatment changes.

“We think sodium MRI is more reflective of the cellular changes in these tumors, which will help us understand if the tumor is responding to treatment right away,” Dr. Bhatia said. “Then, a patient’s medical team can either change or continue on a treatment plan, without needing to wait months for a confirmatory scan.”

While Dr. Bhatia is a clinical radiologist who specializes in interpreting clinical imaging, Dr. Roberts is an imaging physicist who specializes in “imaging algebra” — analyzing multiple MRI images to make sense of their meaning. Together, the pair is among only a few researchers in the world studying sodium MRI to image pediatric brain tumors.

In preliminary studies led by Dr. Bhatia and Dr. Roberts, sodium MRI appears to be a helpful tool for clinical use. When compared to conventional MRI, sodium MRI could help researchers better predict which parts of the tumor in patients’ brains were responding to treatment.

The team’s next research steps will be to validate the technology in larger populations of patients and eventually seek approval from the U.S. Food and Drug Administration to use the tool in non-experimental settings. Dr. Bhatia’s work is supported by the American Brain Tumor Association, the Society of Pediatric Radiology, and the U.S. Department of Defense.

“We’re preparing our clinical scanners at CHOP for sodium MRI,” Dr. Roberts said. “If and when there is sufficient evidence that it works, we will be poised to switch this into clinical practice.”

The Future of Functional Imaging

While sodium MRI is shedding light on how tumors respond to treatment, delta wave MRI is opening a new window into how the brain functions during moments of disruption, such as trauma or psychiatric illness.

The burgeoning technique detects slow brain waves less than 4 Hz, which is in the delta frequency range. It allows researchers to quickly capture brain activity and offers better spatial detail than traditional electrophysiological methods like electroencephalogram (EEG) or magnetoencephalography (MEG). And unlike conventional MRI, delta wave MRI detects abnormal brain frequencies, making it especially valuable for detecting disease or injury. The slow frequency activity appears in many conditions, including Alzheimer’s disease, stroke, and traumatic brain injury (TBI).

“We’re proposing a new MRI imaging technique that, instead of imaging structure or chemicals, is sensitive to the electrophysiology of brain activity,” said Jeffrey Berman, PhD, an investigator in the Department of Radiology. “That’s important for many applications and pathologies where neuronal activity changes.”

Since this technique can image 10 volumes of brain activity every second, researchers like Dr. Berman can observe tiny fluctuations in rhythms and make detailed images.

“This is so innovative, because it shows where functional injury is located,” Dr. Roberts said. “And since something like a TBI can lead to so many symptoms, delta wave MRI has the potential to predict where in the brain certain symptoms are originating from.”

In a proof-of-concept study published in the American Journal of Neuroradiology, Dr. Berman and a team of researchers showed that delta wave MRI was able to capture images every 0.1 seconds while an adult patient was both awake and asleep.

The technique showed that delta waves increased during sleep, which is consistent with what is known from EEG studies, and the study created detailed brain maps during sleep, showing where slow waves were most powerful.

“In the next phase of research, we want to flex the collaborations we have within CHOP and Penn to look at a variety of conditions where slow wave activity is a marker of disease, damage, or severity,” Dr. Berman said.