Clinician researchers at Aarhus University Hospital in Denmark were early adopters of total-body multiparametric PET/CT imaging and are now working with Biograph Vision Quadra™. The team is focused on identifying the critical applications where the precise quantification of tracer dynamics can yield the most significant clinical benefits.
Photography by Gorm Branderup | Data courtesy of Aarhus University Hospital, Denmark
While clinicians rely heavily on static (e.g., single time point) PET/CT imaging with fludeoxyglucose injection F 18 (FDG) for accurate diagnoses and evaluation of treatment paths in many clinical areas, continued innovation in clinical PET/CT imaging is driving an increased utilization of total-body multiparametric PET/CT. This dynamic imaging acquisition method makes it possible for clinicians to measure the true metabolic rate of tracer uptake (MRFDG) rather than using a static image of FDG’s standardized uptake value (SUV) by incorporating a kinetic Patlak model. Having this information can offer clinicians added clarity to distinguish between actual tissue tracer uptake and free tracer in the blood pool. Understanding that difference means the potential to identify false positives that are often diagnosed as residual malignancy in cancers such as lymphoma, breast cancer, and vasculitis, for example.
The combination of multiparametric and Biograph Vision Quadra, a PET/CT system providing a 106-cm large axial field of view (LAFOV) and enhanced sensitivity, is furthering the potential of PET to provide faster and more precise clinical information. Aarhus University Hospital in Denmark is one clinical site who is experienced with these powerful tools. While the road to establishing total-body multiparametric PET/CT imaging and analysis as routine clinical practice may be long, Biograph Vision Quadra is providing Aarhus University Hospital in Denmark new avenues of exploration.
Sharing knowledge and key findings in total-body multiparametric PET/CT
Clinician researchers at Aarhus University Hospital in Denmark were early adopters of total-body multiparametric PET/CT imaging using Biograph Vision™1 PET/CT and are now working with Biograph Vision Quadra. Their pioneering efforts are focused on identifying the critical applications where the precise quantification of tracer dynamics can yield the most significant clinical benefits. The team has shared key findings from their research, but equally important, they’ve shared their work creating a population-based input function to reduce scan time. This has enabled the complex imaging acquisition parameters required for dynamic imaging to be quickly assimilated into clinically routine protocols with minimal additional scan time. Without this important work, total-body multiparametric imaging acquisitions would be more complicated and take much longer, creating a significant barrier to widespread adoption and utilization.
“We made a point to share our population-based input function,” says André Dias, MD, PhD, nuclear medicine physician and staff specialist at Aarhus University Hospital. “So, it’s out there for everyone to use. And it’s set up in a way that people can just download the files and use them on their scanners.”2
In combination with shorter dynamic scan protocols, LAFOV PET/ CT scanners such as Biograph Vision Quadra offer an extended axial field of view and sophisticated software packages that facilitate automatic calculation of multiparametric imaging for analysis and support more widespread use of total-body multiparametric PET/CT imaging. The original acquisition time of 70 minutes has been reduced to 20 minutes, which is comparable to a standard clinical PET/CT scan.
We also try to publish all our observations,” adds Lars Gormsen, MD, PhD, nuclear medicine physician, consultant, and clinical professor at the Department of Nuclear Medicine and PET-Centre of Aarhus University Hospital. “I would have liked to have known the normal values for normal tissue and organs because then I wouldn’t have had to find them myself. But if we can share this information, I think that’s probably a major contribution to the nuclear medicine physicians who are also doing this. We published normal values3 and are publishing repeatability coefficients and the changes we see from test to test so that people can use this information and tailor their future studies. The data can begin to be used on a larger scale as the utilization of total-body multiparametric PET/CT increases.”
The Aarhus team is collecting data for several studies, from lymphoma to breast cancer and inflammation. Some of their research includes larger patient cohorts, such as the lymphoma group, and other studies are on a much smaller scale. In terms of data gathering, the team is committed to publishing as they go and realizes that following long-term patient outcomes can take years.
“We begin with small clinical projects just to learn more about a certain indication and how to evaluate the images,” reports Ole Munk, PhD, professor of medical physics in the Department of Nuclear Medicine and PET-Centre at Aarhus University Hospital, “but it takes time to gather enough data to implement these projects or translate them into routine clinical practice.”
“Other colleagues are also gathering data using total-body multiparametric PET/CT and doing interesting research,” adds Dias. “It will take a lot of patients and a lot of time, so this really needs to be a community effort to gather this data.”
Total-body multiparametric PET/CT for lymphoma
The Aarhus team continues their work on a large lymphoma study, seeing it as the prime candidate for the clinical application benefiting most from dynamic PET/CT imaging at present. Approximately 1,000 lymphoma patients undergo FDG PET/CT scans annually at the Aarhus facility, with dynamic PET/CT images also being acquired alongside each standard scan. An irreversible Patlak model is used to calculate the metabolic rate of FDG uptake.
“Those are the patients we hope will benefit from it,” Gormsen explains. “We’re still gathering data to determine whether we can distinguish between inflammatory reactions in lymph nodes and residual disease in lymphoma. I will look at the standard SUV PET/CT images first, and if there’s something that I’m not entirely sure is actual uptake, I look at the dynamic image and make sure what I’m seeing is real.”
The Aarhus team collaborates with oncology colleagues who are interested in seeing both sets of lymphoma images. Evaluations are based on visual inspection of the images. However, the team believes, and early results indicate, that quantification of tracer dynamics can allow for better discrimination between disease and false positives and that multiparametric images have the potential to aid in that evaluation. The team continues to collect data for the lymphoma study and believes it may be valuable as patients progress through their disease.
“If we want to look at the prognostic value in lymphoma, for instance,” says Gormsen, “you have to wait the three to five years to see the outcome of the patient depending on the lymphoma because some lymphomas have a lot of outcome very rapidly, but for others, we may not get any data for at least one or two years. These studies will generally take a little bit longer because we’re following the patient throughout the progress of their disease.”
Fortifying theranostics with dynamic PET/CT imaging
Theranostics is arguably the most significant recent advancement in precision therapy. As interest and practice in theranostics grow, the demand for more precise quantification to show efficacy also intensifies. With this in mind, the Aarhus team is also investigating the clinical impacts of dynamic imaging with tracers other than FDG.
“We’ve published a paper4 on PSMA prostate cancer in which we looked at two different PSMA tracers, (68Ga) Ga-PSMA-11 and [18F]PSMA-1007, and how multiparametric imaging could influence the image interpretation,” Dias comments. “We’re looking at more precise quantification. The point would be to see if this more precise quantification is parallel to a clinical outcome for the patient and also a treatment response. That’s the kind of study we’re doing both in lymphoma and also in prostate cancer patients.”
“We’re looking at more precise quantification. The point would be to see if this more precise quantification is parallel to a clinical outcome for the patient and also a treatment response.”
Total-body multiparametric PET/CT for breast cancer and vasculitis
The team conducted a small study in breast cancer patients to examine the detectability of malignant lesions using dynamic PET/CT, compared to traditional PET/CT imaging. Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning for these patients. Though standard SUV PET/CT imaging is known to have limited sensitivity for ALN metastases, the findings indicated that dynamic PET/CT has potential in this clinical application. Even with a small cohort, the team found that lesion visibility was best in the dynamic PET/CT images, and three additional lesions were detected that were not seen on the standard SUV PET/CT images.5
In another small study, the Aarhus team measured estrogen receptor (ER) kinetics with total-body multiparametric PET/CT to explore whether dynamic imaging improved quantification and lesion visibility in breast cancer patients. Results indicated that the multiparametric imaging scans offered superior lesion visibility and could potentially aid in correct ER classification and treatment decisions.6
The team hopes that others in the imaging community will begin to utilize total-body multiparametric PET/CT imaging and analysis to gather and share data on potential clinical impact across clinical applications.
In cardiovascular patients, the team uses dynamic PET/CT imaging to subtract the activity in the blood pool and make it easier to see the vessel wall.
“We’ve been looking at low-grade inflammation and large vessel vasculitis,” adds Gormsen. “When you can remove the activity in the blood pool, you can see the discreet increase in residual activity that is normally hard to distinguish. Using dynamic PET/CT imaging, we can much more precisely quantify what’s in the vessel wall. We’re doing this in a study of patients with type 2 diabetes right now. It might be helpful as an adjunct risk tool in patients with diabetes. We can segment the aorta and quantify the low-grade inflammation that is present.”
“Using dynamic PET/CT imaging, we can much more precisely quantify what’s in the vessel wall.”
Vision for a holistic future in total-body multiparametric PET/CT imaging
The Aarhus team continues investigating other clinical areas where total-body multiparametric PET/CT imaging can have a relevant clinical impact. Using Biograph Vision Quadra, they are able to utilize other kinetic models to describe the time-varying distribution of radiopharmaceuticals in the body, which can provide even more clinical insights.
“With Biograph Vision Quadra, we can do more research modeling multiparametric images with different kinds of models because we can see all the organs simultaneously,” explains Munk. “We currently use the irreversible Patlak model but can also use reversible models. This is important because the tracer moves back and forth between tissues, and we can look at correlations across organs. It’s a holistic view of the entire body while evaluating a disease. This is a very big project that we’ve begun.” The team explains their interest in studying the gluco-metabolic connectome, a way of understanding the body’s activities by evaluating metabolic and functional connectivity patterns over time. It is calculated using PET data to measure glucose metabolism and is counterbalanced by metabolic network demand or time-varying FDG delivery.
“The basic idea is that after you scan the patient and only find a tumor in the lung, you’ll focus mainly on that,” Dias notes. “But we believe there are probably also some metabolic changes simultaneously going on in other organs. This might influence the patient’s response to treatment. If you give a chemotherapy agent to a patient who might have a changed metabolism in the liver, where the chemotherapy agent will be deconstructed by the body naturally, that might influence the outcome as well. The idea is to determine if there are any other changes in the connections between the organs and how the organs’ metabolism works or changes while the main disease progresses. By comparing these patients to healthy controls, we can see where there are differences in the metabolism of other organs, not just the organs where they have the disease, which could influence the course of their treatment and outcomes.”
As the field of multiparametric PET/CT imaging continues to evolve, the Aarhus team envisions a future where this technology plays a pivotal role in holistic patient care. With ongoing investigations into diverse clinical areas and the utilization of advanced PET/CT systems like Biograph Vision Quadra, the team anticipates even greater insights and clinical impacts. Their commitment to sharing knowledge and fostering collaboration within the imaging community underscores their vision for a future where dynamic PET/CT imaging and multiparametric PET analysis become indispensable tools in precision medicine, guiding personalized treatment strategies and improving patient outcomes.
“With Biograph Vision Quadra, we can do more research modeling multiparametric images with different kinds of models because we can see all the organs simultaneously.”
About the author
Claudette Lew is a freelance medical writer and editor.
Fludeoxyglucose F 18
Please see Indications and Important Safety Information for Fludeoxyglucose F 18 (18F FDG) Injection.
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