The application of molecular imaging to advance translational research in chronic inflammation

Abstract

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. ¹⁸F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

Keywords: 18F-fluorodeoxyglucose (18-FDG); Atherosclerosis; immunology; inflammation.

Figure 1:

18-FDG PET imaging for the evaluation of inflammatory activity of large and medium-sized arteries. Representative PET images demonstrating 18-FDG uptake in the iliac and femoral arteries (A); popliteal arteries (B); abdominal aortic (C); aortic arch (D); in patient with psoriasis. The mean TBR was 1.26 (0.17) for the suprarenal abdominal aorta, 1.20 (0.16) for infrarenal abdominal aortic, and 1.30 (0.22) for the aortic arch. TBR: tissue- to- background ratio

Figure 2:

18-FDG PET/CT imaging for the evaluation of neural biological activity of the amygdala. Representative fused PET/CT images from a patient with psoriasis who had reduction in psoriatic skin disease activity at baseline (A) and one year (B) showing decreased 18-FDG activity in the amygdala. SUV: standard uptake value

Figure 3:

18-FDG PET/CT imaging for the evaluation of leukopoietic bone marrow activity. Representative fused sagittal PET/CT images from a patient with psoriasis who had reduction in psoriatic skin disease activity at baseline (A) and one year (B) showing decreased 18- FDG activity in T1-L5 vertebrae. SUV: standard uptake value

Figure 4:

Psoriasis as a model to study inflammatory contributions of vascular disease. Psoriasis is a chronic systemic inflammatory disease associated with increased circulating pro-inflammatory cytokines and immune effectors (A), adipose tissue dysfunction (B), lipid profile derangement (C), cellular components, cholesterol crystals and lipoprotein accelerating atherosclerosis (D) and endothelial dysfunction (E).

Figure 5:

18-FDG PET imaging for the evaluation of skin inflammation in psoriasis. Focal areas of extensive skin inflammation related to plaque psoriasis (A) corresponds to similar distribution of areas of 18-FDG uptake on PET (B).

Figure 6:

18-FDG PET imaging demonstrates increased systemic inflammation in psoriasis compared to control. Multifocal areas of increased 18-FDG uptake on PET are observed in a patient with psoriasis (A) compared to control patient (B). 18-FDG uptake is noted within the myocardium (top arrow) within the range of normal variation and also in the kidneys and bladder (bottom arrow), where 18-FDG is excreted. *FDG uptake in the right knee joint (standardized uptake value [SUV], 3.0) and distal right quadriceps tendon, left trochanteric bursa, and left ankle in asymptomatic patient with psoriasis. †Moderately diffusely increased FDG uptake throughout the liver (SUV, 1.64) consistent with increased hepatic inflammation. ‡Diffuse FDG uptake in the aortic wall (SUV, 1.29–1.72) and in the femoral arterial tree, consistent with vascular inflammation. §Focal areas of FDG uptake in skin consistent with inflammation in thick plaques in lower extremities. SUV: standard uptake value

Figure 7:

Vascular inflammation is associated with skin disease severity in psoriasis. Tomographic fused 18-FDG PET/ CT image of the aortic arch from a patient with severe skin disease and control patient (A). Regression plots for multivariable regression analysis of vascular inflammation as measured by target-to-background (TBR) with skin disease severity as measured by psoriasis area and severity (PASI) score. CI indicates confidence interval; and FRS indicates Framingham risk score. The median TBR was 1.6±0.1 for controls and 1.8±0.3 (p<.001). CI indicates confidence interval; and FRS indicates Framingham risk score. TBR: tissue- to- background ratio

Figure 8:

Aortic wall thickness is associated with skin disease severity in psoriasis. Transverse magnetic resonance imaging slices of a patient with mild psoriasis (A) at the level of the descending aorta depicting lower aortic wall thickness when compared with patient with moderate to severe psoriasis (B). The green and the red contours represent the outer and inner border of the aortic wall respectively.

Figure 9:

Aortic vascular inflammation by 18-FDG PET/CT and coronary artery characterization by cardiac computed tomography angiography (CCTA). Frontal coronal section of whole- body 18- FDG PET/CT demonstrating 18- FDG uptake in the aortic wall (A). Transverse section of 18-FDG PET/CT demonstrating vascular inflammation in the aortic wall (B). A panel of reconstructed images from the CCTA demonstrating path of left anterior descending coronary artery (left), depicting noncalcified coronary burden and transverse section of the left descending coronary artery (right). The planar reconstruction (middle) reveals low- attenuation lipid- rich plaque (green and red). The mean TBR was 1.70 [0.26]. TBR: tissue- to- background ratio

Figure 10:

Treatment with biologic therapy for psoriasis is associated with reduction in aortic vascular inflammation. The images show a sagittal section of the level of the mid aorta at baseline (A) and at 1 year after treatment with biologic therapy for psoriasis (B). 18-FDG uptake in the aorta is higher at baseline compared to 1 year after treatment (yellow arrowheads). The mean TBR at baseline was 1.91 [0.29] vs 1.79 [0.22] at 1 year follow up (p<0.001). TBR: tissue- to- background ratio