An experimental imaging technique could help clinicians quickly identify the effectiveness of brain cancer treatment, change therapies if needed, and predict tumor aggressiveness.
An experimental imaging technique could help clinicians quickly identify the effectiveness of brain cancer treatment, change therapies if needed, and predict tumor aggressiveness. Called hyperpolarized magnetic resonance imaging, the technique tracks brain cancer activity by measuring the conversion rate of a glucose intermediate.
Some imaging methods already track cancer cells, which tend to have increased sugar uptake compared to normal cells. By injecting a small amount of radioactive glucose into a vein, a clinician can observe with a PET scan where cells metabolize glucose faster.
“PET tracers can tell us how much sugar is taken up in a cell, indicating a tumor, but it doesn’t say what the cancer cell does with that sugar,” said Kayvan Keshari, a biochemist and imaging specialist at Memorial Sloan Kettering Cancer Center (MSK). “Hyperpolarized MRI can not only trace a cell’s uptake but can also detect when a cancer cell converts it from one form to another. We can detect this rate of conversion in real time and spatially resolved.”
The new imaging technique builds on conventional MRI, which uses radio waves and a powerful magnet linked to a computer to record signals that provide detailed pictures of the body’s interior. Hyperpolarized MRI takes this process a step further by dramatically strengthening the signals.
Keshari’s team exposed the molecules to very low temperatures and irradiated them with microwaves (hyperpolarizing them) before orienting them to an MRI’s magnetic field. The hyperpolarization process boosted the normally weak signal of molecules more than 10,000-fold so they could be more clearly observed. The team optimized the advanced imaging technique, collaborating with colleagues from GE Healthcare, which manufactures a prototype hyperpolarizer.
Earlier research from Keshari’s laboratory showed that hyperpolarized MRI can accurately track metabolism in cancer cells. But brain tumors in patients offered a further challenge. The blood-brain barrier prevents many drugs or other compounds from reaching the brain.
To overcome that barrier, the MSK team developed a solution of pyruvate, a naturally occurring intermediate of glucose metabolism, which is transported through the blood-brain barrier. When exposed to hyperpolarization and metabolized, pyruvate is converted to another substance, lactate, by cancer cells, providing a real-time snapshot of a tumor’s metabolic change. Hyperpolarized pyruvate could become a useful marker for treatment responses in human brain tumors, Keshari said.
The pyruvate solution was placed inside a cryostat and exposed to the extremely low temperature of 1 Kelvin, close to absolute zero.
“With the MRI, we are microwaving the molecule that’s inside of a cryostat that’s inside a superconducting magnet,” Keshari said. “Once the hyperpolarized pyruvate solution is released, it passes though quality control, and then into an IV into the bloodstream of a patient. The pyruvate circulates through the body and goes through the brain barrier within 10 seconds. At that point, a clinical scanner starts imaging every five seconds, providing multi-dimensional data across the human brain. The whole exam lasts about 30 to 40 seconds.”
In this phase 1 study, recently published in Cancer Research, Keshari’s team studied the effect of hyperpolarized pyruvate in four people with brain tumors. The method showed increased pyruvate-to-lactate conversion in untreated tumors and tumors that had returned after treatment. “We can watch the agent come in and measure the conversion rate, which can be spatially resolved,” he said, adding that the patients did not appear to experience ill effects.
“From the time you start the procedure, the engineering must be perfect, a tour de force of optimal control,” Keshari said. “Hyperpolarized pyruvate quickly decays back to its polarization baseline, which is not observable.”
If any part of the engineering does not work properly, scanning can’t be restarted immediately because the signal is gone.
“You would have to repolarize and reinject, and you can’t just keep reinjecting a patient. You have one opportunity to take pictures, and if you don’t, it’s over for the day,” he said. The half-life in the human body is about 15 minutes, and it’s filtered out of the body within 45 minutes to an hour.
To study and refine the new technique through the patient treatment process, Keshari is collaborating with MSK neurosurgeons, neuroradiologists, and other members of the Department of Neurology and the Readiochemistry and Imaging Probe Core Facility. The technology could be developed to become a standard clinical tool available for major hospitals that already have MRI capability, Keshari said. The team hopes to automate the pharmacy preparation of the agent, the scanning, and the image reconstruction so this technology could become affordable and feasible for clinical use.
John Tibbetts is an independent writer who focuses on technology.