I would like to express my sincere appreciation to Strategic Radiology for the support of my research grant, which I hope leads to further scientific advancements in this field and eventually to improving patient care.
Shortly before its 2018 annual meeting, the Radiological Society of North America (RSNA) announced that Sina Tavakoli, MD, had been awarded the inaugural Strategic Radiology-RSNA Research Seed Grant. Dr. Tavakoli will use the $40,000 grant to investigate the role of quantitative 18F-fluoroglutamine PET in non-invasive metabolic imaging of macrophages in atherosclerosis. His attempt to characterize the immunometabolic features of atherosclerotic lesions could eventually lead to the more accurate identification of vulnerable plaques.
Dr Tavakoli’s interest in this line of research began prior to his radiology residency at the Cardiovascular Molecular Imaging Laboratory at Yale University, during which he gained experience that would prove valuable in the design and synthesis of molecular imaging probes targeted at inflammatory processes, as well as their validation in animal models of cardiovascular disease.
Following a 6-year combined residency/PhD program at University of Texas Health Science Center at San Antonio in 2010, Dr. Tavakoli was approved for the ABR Holman Pathway in 2011, which included clinical and research experience, in addition to mentored, graduate-level training in radiation biology and physics of diagnostic imaging. He continued his clinical and research training by joining the University of Washington Cardiothoracic Imaging Fellowship in 2016, and was recruited to the Departments of Radiology (Thoracic Imaging Division) and Medicine (Vascular Medicine Institute) at the University of Pittsburgh in 2017, as a tenure-track assistant professor.
“I strongly believe that the RSNA, through the generous support of its donors, plays a key role in training a new generation of scientists and exploring novel approaches in our field,” said Tavakoli, recipient of an RSNA Research Resident Grant in 2011, Research Fellow Grant in 2016, and most recently, the 2018 SR–RSNA Seed Grant. “I would like to express my sincere appreciation to Strategic Radiology for the support of my research grant, which I hope leads to further scientific advancements in this field and eventually to improving patient care.”
In a Q & A exchange, Dr. Tavakoli provided some intriguing insights into his work for the members of SR.
Strategic Radiology: What precipitated your interest in using PET to characterize atherosclerotic plaques?
Tavakoli: Current clinical imaging of atherosclerosis is primarily based on the detection of the severity of luminal stenosis. However, a large number of plaques that are responsible for development of life-threatening complications of atherosclerosis, such as myocardial infarction and embolic strokes, are caused by plaques that do not cause significant stenosis of the lumen.
There has been a growing effort to focus on the imaging of molecular processes that occur in the “vessel wall” and underlie the progression of plaques and development of complications, rather than their late consequences caused by encroaching upon the “lumen”. This approach, i.e., molecular imaging, allows for early detection of atherosclerosis, risk stratification of patients, and more efficient monitoring of the response to therapies. PET is a very quantitative modality and has a very high sensitivity and versatility compared to other imaging modalities for molecular imaging, which persuaded me to study its role in imaging of atherosclerosis.
Strategic Radiology: You have been pursuing this line of research for more than a decade. What have you discovered during this time?
Tavakoli: Pioneering studies performed over a decade ago have shown the uptake of 18F-FDG, an analogue of glucose used primarily for oncological imaging, in atherosclerotic plaques and other diseases associated with vessel wall inflammation, for example vasculitis. This triggered a large number of investigations to determine the role of 18F-FDG PET as a tool to identify high-risk atherosclerotic plaques and to predict the risk of plaque complications.
Despite some promising results, 18F-FDG PET has not been successfully incorporated into the clinical practice, given the inconsistencies in the results of the clinical studies. Therefore, we decided to explore the immunobiological basis of 18F-FDG uptake in plaques, in particular in the context of the biology of macrophages, which are key inflammatory cells involved in atherogenesis. We have found that 18F-FDG uptake increases in both macrophages which are in a state of pro-inflammatory activation (i.e., contributing to the worsening of vessel wall inflammation) and those that are in an inflammation-resolving state [1,2]. This finding suggests that 18F-FDG uptake as a stand-alone marker may not sufficiently characterize the inflammatory state of atherosclerotic plaques.
As an alternative and complementary approach, we explored the potential of imaging glutamine uptake to improve the identification of macrophage activation states. Our data indicated that combined imaging of 18F-FDG and glutamine uptake allows for a more accurate determination of macrophage activation state in cell culture . We are now aimed to take this approach into the next step by performing in vivo imaging of atherosclerosis using a glutamine analogue tracer, 18F-Fluoroglutamine, in a mouse model of atherosclerosis.
Strategic Radiology: How is your new project different from past investigations and what do you hope to demonstrate/solve/answer?
Tavakoli: Our previous investigations were mostly focused on determining the biological basis of glucose and glutamine uptake in macrophages, as key immune cells in atherogenesis, in cell culture. We are now translating the knowledge acquired in the prior studies to perform the first pilot imaging investigation to evaluate the potential use of combined glucose and glutamine imaging in a mouse model of atherosclerosis.
Strategic Radiology: How do you envision this tool being used in clinical practice?
Tavakoli: 18F-fluoroglutamine is a recently newly developed PET tracer, which has been utilized in imaging of cancer. The tracer has excellent safety profile and has been very promising in oncological imaging. However, its potential role in imaging other disease processes, and specifically atherosclerosis, has not been explored. If the result of the current pilot study is promising in the mouse model, we hope to translate this approach into exploratory clinical studies as the next step.
1. Tavakoli S, Short JD, Downs K,et al. Differential regulation of macrophage glucose metabolism by macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: Implications for 18F FDG PET imaging of vessel wall inflammation. Radiology. 2017 Apr;283(1):87-97. doi: 10.1148/radiol.2016160839. Epub 2016 Nov 16.
2. Tavakoli S, Zamora D, Ullevig S, Asmis R. Bioenergetic profiles diverge during macrophage polarization: implications for the interpretation of 18F-FDG PET imaging of atherosclerosis. J Nucl Med. 2013 Sep;54(9):1661-7. doi: 10.2967/jnumed.112.119099. Epub 2013 Jul 25.
3. Tavakoli S, Downs K, Short JD, et al. Characterization of macrophage polarization states using combined measurement of 2-deoxyglucose and glutamine accumulation: Implications for imaging of atherosclerosis. Arterioscler Thromb Vasc Biol. 2017 Oct;37(10):1840-1848. doi: 10.1161/ATVBAHA.117.308848. Epub 2017 Aug 10.
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