Abstract
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Introduction: Positron-emission tomography (PET) has been used to interrogate biologic hallmarks of arterial wall pathology such as the inflammatory component of atherosclerosis. But the thin target structure and its proximity to blood pool remain challenges for obtaining a robust signal. The recent advent of ultra-sensitive, high-resolution extended field-of-view total-body PET may help to overcome these limitations and open new horizons for atherosclerosis imaging such as long-term imaging of pathophysiology, better understanding of systemic multi-organ interactions or imaging with minimal radiation to the patient.
Methods: Healthy volunteers were imaged serially using the 194 cm axial field-of-view uEXPLORER, for up to 12 hours after a standard dose (372±17 MBq; 1.5h, 3h and 12h p.i.; n=15) of [18F]-fluorodeoxyglucose (FDG) or for up to 3 hours after injection of a very low FDG dose (20±2 MBq; about 5% of a standard dose; 1.5h and 3h p.i.; n=15). A clinical cohort (n=15) undergoing standard FDG PET (307±12 MBq dose) on a conventional scanner with a 22 cm axial field-of-view served for comparison. Arterial wall signal (standardized uptake values (SUVs) and target-to-background ratios (TBRs)) in various arterial segments (i.e., right and left common carotid arteries, ascending aorta, aortic arch, descending thoracic aorta, abdominal aorta, right and left common iliac as well as right and left superficial femoral arteries), crosstalk with lymphoid and hematopoietic organs (i.e., spleen, lymph nodes and bone marrow) and image quality were analyzed.
Results: Total-body PET depicted the large vessel walls with excellent quality and high contrast up to the final time point of 12 hours after FDG injection. Arterial wall signal was mostly stable up to 3h after both standard and low-dose FDG dose injection, and increased significantly at 12h post injection (e.g., aortic SUVmax: 2.68±0.45 at 1.5h p.i. vs 4.58±1.09 at 12h p.i., P<0.0001). The TBR improved over time as blood-pool decreased (e.g., aortic TBR: 1.72±0.18 at 1.5h p.i. vs 16.67±5.58 at 12h p.i., P<0.0001). Ultra-low dose total-body FDG images yielded non-inferior vessel wall signal (SUVmax and TBR) compared to conventional short axial field-of-view PET. Moreover, crosstalk between vessel wall and hematopoietic and lymphoid organs was reliably identified, with superior accuracy in both total-body PET cohorts, compared to conventional short axial field-of-view PET. PET, particularly in high-quality early images (e.g., arterial wall signal vs lymph node signal: r=0.37 (95% CI, -0.18 to 0.74), P=0.1779 in conventional PET vs r=0.67 (95% CI, 0.25 to 0.88), P=0.0058 in standard dose TB PET at 1.5h p.i.). Image noise increased in ultra-low-dose total-body PET and at late imaging time points (P<0.0001 in all cases).
Conclusions: Ultra-sensitive, high-resolution total body PET enables detailed assessment of in vivo vessel wall biology and its crosstalk with other organs, over an extended time window after tracer injection or at ultra-low tracer dose. These initial observations support the feasibility of serial imaging in low-risk populations, and they will stimulate future studies assessing global disease scoring, imaging-based stratification for therapy and repeat imaging for treatment monitoring in atherosclerosis and other vascular diseases.