After treatment, families often wait for MRI results with one painful question hanging over everything:
What are we really seeing?
Is the tumor active? Is it treatment-related change? Are aggressive cells still there before a standard scan can clearly show what is happening?
A Cure Starts Now-funded research project at Johns Hopkins is exploring a new way to answer those questions.
Dr. Jeff Bulte and his team are studying whether a specialized MRI technique can detect biological signs of some of the most aggressive cells in brain tumors, including DIPG/DMG. The goal is straightforward, even if the science is complex: help doctors see what standard MRI scans may be missing.
If successful, this research could one day give physicians a clearer picture of which tumor cells remain active after treatment, whether disease is returning, and when additional intervention may be needed.
Why Standard MRI Does Not Tell the Whole Story
Standard MRI scans are essential in brain tumor care. They help doctors see where a tumor is located, how large it is, and whether it appears to be growing or shrinking.
But structure is only part of the story.
After radiation or other treatment, conventional MRI can sometimes struggle to distinguish between active tumor growth and treatment-related changes in the brain. Families may hear words like swelling, inflammation, necrosis, progression, or pseudoprogression, all while waiting for clarity on what is actually happening.
Dr. Bulte’s work focuses on a different question:
Can MRI show tumor biology, not only tumor anatomy?
Instead of only looking at the size or shape of a tumor, his team is investigating whether MRI can help identify aggressive tumor cells based on biological features those cells carry.
The Tumor’s “Sugar Signature”
At the center of this research is a naturally occurring sugar called mannose.
Dr. Bulte’s team found that particularly aggressive cancer stem cells appear to carry unusually high levels of mannose and related sugars on their surface. Those sugars create a kind of biological signature.
The team first studied this in glioblastoma, an aggressive adult brain tumor. In patient tumor samples, the most aggressive tumor cells consistently carried this sugar-related signature. When researchers grew those cells in the laboratory and scanned them using MRI, the cells produced a distinct signal not seen in less aggressive tumor cells.
The team then tested the idea in animal models. Again, the MRI signal appeared in areas associated with aggressive tumor cells. To confirm the signal was connected to the sugar signature itself, researchers reduced the sugar content on the surface of the cells. When they did, the MRI signal decreased.
Those findings, recently published in Science Advances, gave the team strong evidence that this imaging method was detecting a real biological feature of aggressive tumor cells.
What Is HPTW MRI?
The specialized MRI technique being studied is called hydroxyl proton transfer-weighted MRI, or HPTw MRI.
Fortunately, the concept is easier to understand than the name.
Sugars contain chemical structures called hydroxyl groups. HPTw MRI is designed to detect signals associated with those sugar-related structures. Early in the research, the team believed the method was primarily detecting mannose. As the work progressed, they found other sugars may also contribute to the signal.
So instead of describing this as “mannose imaging,” the researchers now describe it as a broader sugar-sensitive imaging approach.
The purpose is not simply to see the tumor. The goal is to identify the cells most responsible for tumor growth, treatment resistance, and recurrence.
Bringing This Research to DIPG/DMG
After seeing promising results in glioblastoma, Dr. Bulte’s team began asking whether the same concept could apply to DIPG/DMG.
Using patient-derived DIPG/DMG cell lines, the researchers began studying whether these tumors carry similar sugar-related characteristics.
The early findings are encouraging. The team has already confirmed that DIPG/DMG cells show the abnormal sugar signatures and cellular characteristics they were hoping to find. That suggests some of the same biological features seen in aggressive glioblastoma cells may also be present in DIPG/DMG.
Now, the team is evaluating the imaging technique in preclinical DIPG/DMG models. Much of that work is expected to continue over the next year.
At the same time, researchers have built the infrastructure needed to begin studying this technique in patients through Johns Hopkins and the Kennedy Krieger Institute.
Is This a Treatment Trial?
No. The clinical studies being planned are focused on imaging, not therapy.
When families hear “clinical trial,” they often think of a new drug or experimental treatment. This research is different.
The first goal is to learn whether the MRI findings seen in the laboratory can also be detected in patients. Researchers will study what the scans reveal and whether those findings match what is known about the disease.
Over time, this information may help guide treatment decisions. But these early studies are designed to better understand the imaging technique itself and learn how much useful information it can provide.
Every patient who participates helps researchers build critical knowledge that could improve the way physicians monitor these tumors in the future.
Why This Could Matter for Families
One of the hardest parts of brain tumor care is uncertainty.
A scan changes. A spot appears. Swelling increases. The tumor looks different. Families are left waiting to learn whether the change means active tumor, treatment effect, radiation injury, or something else entirely.
Dr. Bulte hopes this imaging approach could eventually provide more specific answers.
Because the sugar signature appears to be associated with living, aggressive tumor cells, the technique may help physicians identify residual disease or early recurrence sooner than current imaging methods allow.
Instead of relying only on indirect signs of tumor activity, doctors may one day be able to detect the cells most likely to drive progression.
In glioblastoma studies, Dr. Bulte’s team has already observed that this imaging technique highlights areas that look different from what appears on standard MRI scans. That suggests the technology may be capturing biological information conventional imaging cannot show.
If physicians can identify aggressive tumor cells earlier, they may be able to adjust treatment plans sooner rather than waiting for changes to become visible on standard imaging.
In the future, this could help inform decisions about additional radiation, chemotherapy, or other therapies when aggressive tumor cells remain present.
The technology could also have value in brain tumors where surgery is possible. If physicians can better identify the boundaries of aggressive tumor tissue, they may be better equipped to remove as much tumor as possible while protecting surrounding healthy brain tissue.
For families facing DIPG/DMG, one of the most important possibilities is clarity. Researchers hope this approach may eventually help distinguish between recurrent tumor and treatment-related effects such as radiation necrosis.
That distinction is painful, complicated, and deeply important. A clearer scan could mean clearer decisions.
What Still Needs to Happen?
Although the early findings are promising, this technology is not ready for routine clinical care yet.
Researchers still need to validate that what they see on MRI truly corresponds to aggressive tumor cells. That means comparing imaging findings with tumor tissue samples, blood biomarkers, and other biological measurements.
They also need to determine whether using this information improves patient care. The long-term question is whether earlier detection of residual or recurrent disease can help physicians make better treatment decisions and improve outcomes.
Because DIPG/DMG is rare, gathering enough patient data takes time. Eventually, researchers hope multiple institutions will participate in larger studies to determine whether this imaging method should become part of standard care.
Why This Research Could Be Practical
One of the most encouraging parts of this work is its potential practicality.
Dr. Bulte explained that many hospitals already have MRI systems capable of performing similar advanced imaging techniques. If future studies show clinical value, adoption may not require major investments in new equipment.
Researchers around the world have also developed guidelines for performing and interpreting related imaging methods. That means hospitals may eventually be able to incorporate this approach into existing MRI programs more easily than many people might expect.
There is still a long road ahead. But if this research continues to move forward, the path to broader use may be more realistic than with technologies requiring entirely new equipment or infrastructure.
The Role of Philanthropy
In a recent conversation with The Cure Starts Now, Dr. Bulte explained the role philanthropy plays in helping researchers move innovative ideas from the laboratory toward patient care.
His answer reflected something we often hear from investigators.
Traditional government funding can take years to secure. It often favors projects with substantial preliminary data. New ideas, especially high-risk and high-reward ideas, can struggle to receive support through conventional funding channels.
The Cure Starts Now funding allowed Dr. Bulte’s team to begin this work quickly after approval. Instead of waiting months or years for funding decisions, they were able to start generating data, testing the concept, and building momentum.
That is what research funding makes possible. It helps bold ideas move faster and gives scientists the chance to test questions others may not fund yet. It creates the early evidence needed to bring promising approaches closer to the children and families who need them most.
We are grateful to Dr. Bulte and his team for their dedication to advancing new approaches for DIPG/DMG. We look forward to sharing more as this important work continues.