Powerful New Brain PET Scanner Is Opening New Research Pathways

At the Yale Positron Emission Tomography (PET) Center, an ultra-high-performance brain-dedicated scanner called the NeuroEXPLORER (NX) is redefining what is possible in brain PET imaging.

With a 10-fold sensitivity increase and over two times the spatial resolution of the previous state-of-the-art brain PET scanner, the NX can detect signals from much smaller structures, imaging them in greater detail. This could allow for earlier disease detection and open new research opportunities to study conditions like Alzheimer’s disease, Parkinson’s disease, and brain cancer.

Yale School of Medicine (YSM) researchers are now demonstrating what this increased resolution and sensitivity can enable, with recently published findings in the European Journal of Nuclear Medicine and Molecular Imaging and the Journal of Nuclear Medicine.

“It’s very exciting,” says Richard Carson, PhD, professor of radiology and biomedical imaging at YSM and one of the principal investigators behind the development of the NX. “This opens the door to perform studies which we would not have dreamed of doing before.”

In the new studies, the research team compared the NX to the High-Resolution Research Tomograph (HRRT), the previous state-of-the-art brain-dedicated PET scanner. They also tested whether the NX could provide an alternative to the invasive arterial blood sampling required for quantitative PET research.

Installed at Yale in 2023, the NX was developed through a collaboration between researchers at YSM, the University of California-Davis, and United Imaging Healthcare of America.

“We were excited to finally see how the NX is performing in real-world scenarios,” says Tommaso Volpi, MD, PhD, a postdoctoral associate in Carson’s lab and lead author of the two new studies. “The whole PET community has been involved in formulating a list of which applications they wanted to see first addressed on the NX, and these two studies were definitely on their (and our) bucket list.”

To directly compare NX and the HRRT, Volpi and the team scanned the brains of seven participants using seven different radioactive tracers. Radioactive tracers are administered to patients before their scan, and they emit signals that are detected by the PET scanner and converted into images of the brain. A wide variety of tracers have been used in these studies, targeting many functions in the brain, including glucose metabolism and neuroreceptor/transporter density.

The results were striking. “You can really visualize these interesting structures that before you wouldn’t see,” Volpi says. “If you just look at these images, you can see how detailed they are, and how much exciting information we can extract from them.”

For example, when looking at a tracer that targets receptors for dopamine, an important neurotransmitter in the brain, the NX showed the entire mammillothalamic tract, an important part of a circuit involved in spatial navigation and memory. The substantia nigra, a dopamine-producing brain region heavily implicated in Parkinson’s disease, was also clearly visible. With the HRRT, Volpi says, you would only get a glimpse of these structures.

“If a neurologist can actually look at these detailed structures and assess whether this is a healthy individual or a patient with Parkinson’s disease, it could have very substantial impact,” he adds.

Given NX’s capacity to produce such high-resolution images, Volpi and his team were also interested in testing its ability to measure activity from small blood vessels feeding the brain, an essential piece of data in quantitative brain PET research.

Researchers need to know how much tracer is in the blood in order to accurately model what is happening in the brain. Typically, this would be measured with blood samples, but this process is both invasive for patients and cumbersome for researchers and clinicians. There’s been growing interest in using image-derived measurements instead, wherein the PET scanner itself is used to assess tracer levels and generate what is known as a blood time-activity curve. With such high resolution, the NX was able to do just that.

“With previous scanners, you just don’t have good enough resolution to really image the blood activity,” Volpi says. “But with the NeuroEXPLORER, the early blood peak is correctly recovered for the first time.”

This early phase blood time-activity curve refers to the first minutes after tracer is administered, where the blood activity is very high. While the late phase of the curve still needs additional work, the early phase could be used to quantify the delivery of the tracer, which can serve as a measure of cerebral blood flow.

“This is a first step that was just not available to brain PET before,” Volpi says.

The unique engineering behind the NX is responsible for its success. The scanner was designed to have a longer field of view, which means it can image a larger area than a standard brain PET scanner, i.e. not just the head but also the entire neck. It also has smaller detector elements, which consist of crystals inside the PET scanner that detect the radioactive signals from the tracer. Decreasing the size of those crystals allows the scanner to more precisely pinpoint the location of the radiation inside the brain.

The researchers also added a feature called “depth of interaction,” which shows the exact location where the radiation interacts with the crystal, creating higher-resolution brain images.

With such high sensitivity, less radioactive tracer is needed to generate a high-quality brain image. This could allow researchers to study the developing adolescent brain, as the amount of radiation will now be well below the safety limits for this age group.

“Diseases like autism and schizophrenia really evolve in the childhood and teenage years. Right now, studies in these areas are done after you’re 18 years old when the radiation risks are presumed to be low,” says Carson, who is also a professor of biomedical engineering at Yale School of Engineering. “Now that we can drop the radiation dose down by a factor of 10 or more, we have the potential to open these research areas.”

The high sensitivity and resolution of the NX might also allow clinicians to see how well a brain tumor is responding to treatment by distinguishing what could be a recurring tumor from what might be just treatment-induced inflammation, a differentiation that has typically been very difficult to make. Simultaneous tracking of neurotransmitters and synapses could provide insights into the mechanisms of Parkinson’s disease, and early identification of small brain regions implicated in Alzheimer’s disease; longitudinal follow-ups with those patients could provide insights into the progression and potential differential diagnoses of the disease.

“The ability to follow patients with this high sensitivity allows us to make a more accurate and precise measurement, and we can see small changes or see them in a shorter period of time, and that’s going to be just incredibly exciting and impactful,” says Carson.