The Whole Picture
By Dan Harvey
Vol. 20 No. 6 P. 10
Advances in PET/CT integration are paving the way for faster, more complete imaging.
PET has long been perceived as the best imaging modality for noninvasive functional imaging due to its sensitivity. Still, PET presented certain challenges related to signal-to-noise ratio—which affects image quality, radiotracer dose amounts, and extended imaging times that can cause patient discomfort.
Recent technological developments have addressed—and even have appeared to overcome—these challenges. Building on earlier integration of PET with CT (PET/CT), these more recent advancements promise to change the way PET can be used in clinical practice and research. The developments are referred to as either whole-body or total-body PET/CT.
United Imaging Healthcare (UIH) is pioneering the concept of total-body PET/CT, which enables clinicians to place a patient’s body in a field of view that provides simultaneous imaging of all organs and tissues. It increases clinical throughput by accomplishing the work of three or four conventional PET scanners. In December 2018, UIH received FDA clearance for its total-body scanner, which can rapidly provide a 3D image of the entire human body in one bed position. The new technology produces a comprehensive scan in 30 seconds or less, which is about 40 times faster than conventional PET technology.
Development of this total-body technology began with a multi-institutional consortium led by researchers at UC Davis. This consortium was headed by Simon Cherry, PhD, a professor in the UC Davis department of biomedical engineering, and Ramsey Badawi, PhD, chief of nuclear medicine and a professor in the department of radiology at UC Davis.
Cherry is emphatic about referring to the UIH technology as total body, as opposed to whole body. “The ‘whole body’ terminology indicates that you place and then move the patient, in sequential fashion, through the scanner, imaging the body section by section, so to speak,” he explains.
The resulting images, he says, are then “stitched together” to form an image of the “whole body.” Such “whole-body” PET imaging has been done for decades, he says, but what the consortium and its industry partner are doing is substantially different.
“We’re capturing signal from the entire body at once,” Cherry says. “The patient doesn’t have to be moved through a scanner. Every organ and all tissue are imaged at the same time. That’s a considerable distinction from what was being done before.”
Cherry and Badawi and their team began working on the scanner development in 2011, after receiving a grant from the National Cancer Institute. In 2015, a grant from the National Institutes of Health (NIH) enabled them to move forward. But the initial idea goes back to 2005, Cherry says.
“We were working on the concept for a long time, and the NIH funding enabled us to develop the first total-body PET/CT scanner prototype,” he says.
From there, the UC Davis consortium wanted to collaborate with an industry partner. A relationship with UIH proved to be the most viable. UIH is an international company headquartered in Shanghai, China, with subsidiaries across the world, including the United States.
“We chose UIH in 2016 because the company was committed to turning the concept into a product,” Cherry recalls.
“Collaboration is important in bringing new ideas to life,” says Jeffrey M. Bundy, PhD, CEO of UIH Solutions, North American operations. “Academic partnerships and funding from organizations like NIH are critical. In this case, the NIH was a big catalyst. By working closely together with a common goal of patient care, we have reached a place where this technology has moved out of the prototyping phase into commercial product.”
“We’ve made the system available very quickly by building upon UIH’s existing technology,” Cherry says. “When you talk about speed, in terms of development, here we are in 2019, just three years after our first discussion with UIH, with the scanner built, approved, and available.”
The first human images were presented at RSNA 2018. As described in a report recently published in the Journal of Nuclear Medicine, the technology—branded EXPLORER—features an axial field of view of 194 cm and a transaxial field of view of 68.6 cm. The PET element, which includes lutetium oxyorthosilicate detector crystals decoded by silicon photomultipliers, was integrated with an 80-row, 160-slice CT scanner.
Bundy sums it up by explaining that the technology provides one-stage, simultaneous real-time imaging, rather than imaging done with multiple stages. “That’s the big difference, and not with just PET but with any tomographic imaging modality,” he says.
With its 194-cm field of view, the EXPLORER PET/CT can image the total human body in a single acquisition. This enables rapid, total-body pharmacokinetic studies. It captures significantly more of the available signal compared with conventional techniques, which enables clinicians to scan more quickly, as opposed to about 20 minutes, Cherry says. Because it can be hard for any patient to stay completely still for nearly half an hour, the reduced scan time improves patient comfort and satisfaction as well as image quality. Also, users can scan patients with much lower amounts of radiotracer, resulting in a lower radiation dose.
“This is very important for certain patient populations—the pediatric population, for example—where dose is a critical consideration,” Cherry says.
“But these developments are beneficial to any patient,” Bundy adds. “So even though this system takes much less time than a typical PET or MRI scan, we have looked at how to improve the patient experience. For instance, we have explored the possibility of allowing patients to watch videos while inside the scanner, to ease their minds during the procedure.”
Improved image quality is a substantial benefit, Cherry says. “That will help clinicians see small tumors and detect earlier low-grade disease. The hypothesis is that better images will enable us to see a lot more.” He says better images will raise more questions and, at the same time, help to answer those questions. While that claim may need to be supported by more research, Cherry believes that the technology will enable what he calls “a totally new clinical paradigm” as well as expanded research possibilities.
“With an imaging technique that provides simultaneous, entire body imaging, if we want to look at a new drug’s distribution throughout the body from the time after injection, we will be able to watch the concentration of the drug in every organ and tissue over time,” Cherry says. “Previously, we had no technique that could do that. This development will open up a whole host of research opportunities.”
Single Stage, Multiple Audiences
The partners—the consortium developers and UIH—anticipate a wide range of applications. Beyond oncology, they envision the scanner being utilized to determine blood flow throughout the body, better recognize and study inflammation, and provide increased understanding of infections as well as immunological and metabolic disorders.
“We’re also anticipating the technology being applied to neurodegenerative disease, cardiology, and conditions where multiple organs are involved,” Bundy says.
One large question remains: Is this technology poised to move into the mainstream and, if not yet, how long will it take for widespread implementation to happen? In April 2019, the first scanner was installed at UC Davis. Bundy indicates that, at present, that has been the only installation.
“It’s going into one of [UC Davis’] clinical facilities,” he says, “but the technology will also be used for research and exploration purposes.”
What happens beyond that is hard to say, as many forces come into play when implementing new technology, Cherry says. He doesn’t think anyone questions the new clinical and research opportunities that the scanner offers, but there’s also an economic factor: These new scanners will be expensive.
“Hospitals tend to make decisions several years ahead of time, as far as replacing equipment. Think of it as a turnover time,” he says. “I don’t know how the economics will work out.”
Cherry says that there are two arguments in the arena. One says that the equipment is far too expensive and will never see widespread clinical usage. The second says that the cost of the instrument is only a small part of the cost of providing a PET scanning service. The fact that the scanner can scan more quickly means higher throughput, so it may be quickly adopted.
“The economics could be much more favorable than some people realize, especially in centers that have high patient volumes. But those are two extremes of an argument,” Cherry says, adding that we’ll just have to “wait and see.”
Meanwhile, UIH has been talking about implementation with many clinical institutions, both research institutions and hospitals, Bundy says. Anticipating increased dissemination of its technology, UIH is building a 100,000-square-foot manufacturing and customer support space in Houston for increased EXPLORER production.
A similar presentation—one that involved whole-body PET/CT imaging—was featured at RSNA 2018. It was centered on technology developed by Philips. Michael Knopp, MD, PhD, a professor of radiology and Novartis Chair of Imaging Research at The Ohio State University Wexner Medical Center, presented the results of a phase 2 clinical trial.
Knopp related that the phase 1 study was a preliminary feasibility study, and the phase 2 study built upon the previous findings. The researchers utilized technology that allowed a whole-body scan in at least two minutes. Knopp reports that the study was completed in 2018, and its main purpose was to evaluate the capabilities of the new approach, specifically, to see how it would be a viable alternative in the assessment of biodistribution and activities in a kinetic fashion.
The study focused on two primary populations that could benefit from “ultrafast” imaging. The first was claustrophobic people who were suffering pain. The second was pediatric patients, to see whether they could be successfully imaged under mild sedation instead of anesthesia. “We wanted to see if we could leverage digital PET technology and advanced reconstruction to perform such rapid imaging,” he explains.
The intraindividual study was designed to compare new-generation digital PET/CT with conventional systems. The researchers found that by “freezing motion” to a much larger extent, they could leverage the precision of improved detectability to provide image quality equivalent to conventional PET/CT in just one-tenth of the acquisition time, Knopp reports.
The researchers used Philips’ Vereos PET/CT solution; the machine features the company’s proprietary digital photon counting technology. “It was a more conventional system than what was used in the EXPLORER projects, but it still provided ultrafast imaging, which means that a patient doesn’t have to be positioned inside a tube,” Knopp says.
“[UIH’s] product is similar to an MR system, where the patient needs to be placed completely inside the imaging tube, but that makes such a system much more expensive, when you compare it to conventional PET systems,” Knopp says. “What we showed with the technology we used was that it was possible to do similar things with digital PET/CT.”
Although photon-counting CT is still considered an emerging technology, it allows for reduced radiation exposure, better resolution, decreased problems with artifacts, and alternative protocols related to injected agents. Its potential appears to be substantial.
Both Philips and UIH use solid-state detectors; silicon chips advance the detection capability, but each company has slightly different implementation of photon counting.
Knopp clarifies the difference between UIH’s and Philips’ approaches: “The EXPLORER project was basically ring after ring after ring, so that you have a z-axis that covers the entire body, similar to an ultralong MR with considerable extension of detection, so the patient is surrounded within the system. Many patients consider this confinement. The Philips system is open. Still, clinicians can acquire images extremely fast.”
Knopp says it takes about nine seconds for every 16 cm to acquire a whole-body acquisition. “That means we were able to image the whole body within two minutes. The Philips solution has very good resolution for time of flight, and its optimized reconstruction provides excellent image quality.”
Knopp says decisions about which systems to purchase are often based on cost. New developments, such as the EXPLORER, can be “three to four times more expensive than a conventional system.” But he is not denigrating the achievement of the UIH advancement.
“I think the EXPLORER project represents a fantastic technological development, one that provides additional insight into whole-body distribution, but when we are talking about clinical implementation—how we want to use it for patient care—I think our approach with the Philips technology is more practical and more feasible, and that’s because of the cost,” Knopp says.
In addition to cost, patient comfort is also an important consideration. “No patient likes to feel enclosed,” he says, adding that a relaxed patient leads to better image quality. “I think the approach we are taking is more feasible on how to translate some of these elements into clinical, day-to-day operations,” Knopp says.
As implementation is not yet widespread, the jury is still out about which method will achieve widespread use, but Knopp adds a point that’s hard to debate.
“The key point is that these new technologies allow PET to move forward into new and different directions,” he says. “PET should prove to be an even more important tool in the clinician’s set of imaging technologies.”
— Dan Harvey is a freelance writer based in Wilmington, Delaware.