Figure - available from: European Journal of Nuclear Medicine and Molecular Imaging
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Long-term observation of hot spots. a On the baseline CT image, macrocalcification is not apparent on the right wall of the aorta. b On the PET image, the ¹⁸F-NaF-avid site is apparent on the right wall of the aorta (TBRmax 2.13, bsNaFmax 1.37). c On the follow-up CT image after 970 days, macrocalcification appears consistent with the location of ¹⁸F-NaF uptake on the PET image (CVS 17, CTmax 408, CTmean 235.9)
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Purpose:
Our aim was to assess whether (18)F-NaF PET/CT is able to predict progression of the CT calcium score.
Methods:
Between August 2007 and November 2015, 34 patients (18 women, 16 men; age, mean???standard deviation, 57.5???13.9?years; age range 19-78 years) with malignancy or orthopaedic disease were enrolled in this study, with approxima...
Citations
... Most studies on the use of PET for the quantitative assessment of atherosclerosis have been conducted with the 18 F-NaF radiotracer, which has been validated as a marker of calcification and disease activity using histology as the reference standard 27 (Fig. 7). The uptake of 18 F-NaF is closely associated with disease progression and a change in CAC scores 126 . Importantly, baseline 18 F-NaF levels can help to identify the culprit plaque, whereas total coronary microcalcification activity can independently predict subsequent fatal or non-fatal MI 125 . ...
The detection and characterization of coronary artery stenosis and atherosclerosis using imaging tools are key for clinical decision-making in patients with known or suspected coronary artery disease. In this regard, imaging-based quantification can be improved by choosing the most appropriate imaging modality for diagnosis, treatment and procedural planning. In this Consensus Statement, we provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations and describe the advances in imaging technology. Clinical consensus recommendations on the appropriateness of each imaging technique for direct coronary artery visualization were derived through a three-step, real-time Delphi process that took place before, during and after the Second International Quantitative Cardiovascular Imaging Meeting in September 2022. According to the Delphi survey answers, CT is the method of choice to rule out obstructive stenosis in patients with an intermediate pre-test probability of coronary artery disease and enables quantitative assessment of coronary plaque with respect to dimensions, composition, location and related risk of future cardiovascular events, whereas MRI facilitates the visualization of coronary plaque and can be used in experienced centres as a radiation-free, second-line option for non-invasive coronary angiography. PET has the greatest potential for quantifying inflammation in coronary plaque but SPECT currently has a limited role in clinical coronary artery stenosis and atherosclerosis imaging. Invasive coronary angiography is the reference standard for stenosis assessment but cannot characterize coronary plaques. Finally, intravascular ultrasonography and optical coherence tomography are the most important invasive imaging modalities for the identification of plaques at high risk of rupture. The recommendations made in this Consensus Statement will help clinicians to choose the most appropriate imaging modality on the basis of the specific clinical scenario, individual patient characteristics and the availability of each imaging modality.
... Beyond prediction of myocardial infarction 18 F-NaF PET can also predict progression of the disease [51][52][53]. In three independent studies, increased 18 F-NaF uptake was associated with more rapid progression of coronary atherosclerotic calcification. ...
Non-invasive testing plays a pivotal role in the diagnosis, assessment of progression, response to therapy, and risk stratification of coronary artery disease. Although anatomical plaque imaging by computed tomography angiography (CTA) and ischemia detection with myocardial perfusion imaging studies are current standards of care, there is a growing body of evidence that imaging of the processes which drive atherosclerotic plaque progression and rupture has the potential to further enhance risk stratification. In particular, non-invasive imaging of coronary plaque inflammation and active calcification has shown promise in this regard. Positron emission tomography (PET) with newly-adopted radiotracers provides unique insights into atheroma activity acting as a powerful independent predictor of myocardial infarctions. Similarly, by providing a quantitative measure of coronary inflammation, the pericoronary adipose tissue density (PCAT) derived from standard coronary CTA enhances cardiac risk prediction and allows re-stratification over and above current state-of-the-art assessments. In this review, we shall discuss the recent advances in the non-invasive methods of assessment of disease activity by PET and CTA, highlighting how these methods could improve risk stratification and ultimately benefit patients with coronary artery disease.
... In addition, Ishiwata et al. recorded the initial arterial NaF uptake in the abdominal aorta and common iliac arteries and then tracked the atherosclerotic disease progression using CT. They observed that, on index scans, NaF uptake was greater in noncalcified than calcified lesions, perhaps reflecting active plaque deposition; however, the initial NaF findings did not correlate with the disease burden determined by CT alone during follow-up at 1 to 2 years [55,58]. ...
Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) represents a method of detecting and characterizing arterial wall inflammation, with potential applications in the early assessment of vascular disorders such as atherosclerosis. By portraying early-stage molecular changes, FDG-PET findings have previously been shown to correlate with atherosclerosis progression. In addition, recent studies have suggested that microcalcification revealed by 18F-sodium fluoride (NaF) may be more sensitive at detecting atherogenic changes compared to FDG-PET. In this review, we summarize the roles of FDG and NaF in the assessment of atherosclerosis and discuss the role of global assessment in quantification of the vascular disease burden. Furthermore, we will review the emerging applications of FDG-PET in various vascular disorders, including pulmonary embolism, as well as inflammatory and infectious vascular diseases.
... Y. Ishiwata et al., who examined 34 patients, showed that the accumulation of sodium fluoride can predict the progression of vascular calcification, which in turn is a predictor of vascular catastrophes during the year after the PET/CT investigation [69]. A study of 293 patients, using PET with fluoride, showed not only its prognostic significance but also the possibility of using machine learning systems to predict the risk of cardiovascular events [70]. ...
Atherosclerosis is a well-known disease leading to cardiovascular events, including myocardial infarction and ischemic stroke. These conditions lead to a high mortality rate, which explains the interest in their prevention, early detection, and treatment. Molecular imaging is able to shed light on the basic pathophysiological processes, such as inflammation, that cause the progression and instability of plaque. The most common radiotracers used in clinical practice can detect increased energy metabolism (FDG), macrophage number (somatostatin receptor imaging), the intensity of cell proliferation in the area (labeled choline), and microcalcifications (fluoride imaging). These radiopharmaceuticals, especially FDG and labeled sodium fluoride, can predict cardiovascular events. The limitations of molecular imaging in atherosclerosis include low uptake of highly specific tracers, possible overlap with other diseases of the vessel wall, and specific features of certain tracers’ physiological distribution. A common protocol for patient preparation, data acquisition, and quantification is needed in the area of atherosclerosis imaging research.
... In a 19 oncologic patients experience, the NaF uptake measured as TBRmax, significantly increased from baseline (2.5 ± 0.8) to follow-up (2.8 ± 0.7, P < 0.05) with a corresponding increased calcium density increased [161]. Ishiwata et al. reported a significant correlation between baseline calcification vessel wall NaF uptake activity and the change after 1 year in terms of calcification volumetric score also as a predictor of future cardiovascular disease risk, in absence of new macrocalcification [162]. Further longitudinal studies are crucially needed to explore whether NaF accumulation precedes the development of overt arterial calcification, and to define the reproducibility and stability of NaF signal in coronary and carotid arteries, also in the coronary stenosis severity assessment (Fig. 4.7) [163]. ...
Many cellular and molecular pathways are involved in the pathogenesis of vulnerable plaque. The developing role of new nuclear medicine imaging techniques surpassed the conventional morphological evaluation, permitting the assessment of specific bio-molecular targets involved in the plaque pathogenesis. The most widely diffuse tracer in PET imaging is 18FDG. 18FDG-PET has the potential to diagnose and monitor the inflammatory activity of macrophages within the atherosclerotic plaque and could serve for the prognostic evaluation of these lesions. Further PET imaging applications have been evaluated for precise assessment of the CXCR4-expressing plaque burden of the vessel wall that may allow for more reliable identification of patients that would most likely benefit from innovative CXCR4-targeting therapies. In this setting, 68Ga-Pentixafor PET/CT identified a broad spectrum of coronary plaques, including stented culprit, stented non-culprit, non-stented non-culprit coronary lesions. Another clinical prominent characteristic of atherosclerosis is the presence of calcium deposition that may be also assessed using NaF PET. The tracer uptake of NaF has been demonstrated to be microscopically correlated with calcification (instead of inflammation) and potentially useful in risk’s stratification of patients. Recent research has focused on the development of smart imaging radiotracers targeting specific agents/biomarkers as favorable targets for in vivo assessment of angiogenesis. Nuclear medicine advancements have been proposed in preparations of 18F-labeled, 64Cu-labeled, and 68Ga-labeled RGD PET tracers, for imaging receptor integrin αvβ3 expression but the translation in clinical practice is still limited. Another particular target of the atherosclerosis is the macrophagic activation in atherosclerosis process and the somatostatin receptor expression. The subtype 2 of somatostatin receptor has been shown to be upregulated on the surface of pro-inflammatory M1 macrophages. SSRT-2 receptor PET imaging, able to target activated inflammatory cells, appears to be a possible valuable alternative to 18F-FDG PET/CT, opening a possible future scenario for theranostic application.
... In a 19 oncologic patients experience, the NaF uptake measured as TBRmax, significantly increased from baseline (2.5 ± 0.8) to follow-up (2.8 ± 0.7, P < 0.05) with a corresponding increased calcium density increased [161]. Ishiwata et al. reported a significant correlation between baseline calcification vessel wall NaF uptake activity and the change after 1 year in terms of calcification volumetric score also as a predictor of future cardiovascular disease risk, in absence of new macrocalcification [162]. Further longitudinal studies are crucially needed to explore whether NaF accumulation precedes the development of overt arterial calcification, and to define the reproducibility and stability of NaF signal in coronary and carotid arteries, also in the coronary stenosis severity assessment (Fig. 4.7) [163]. ...
Acute myocardial infarction is one of the leading causes of death in the western world. Timely implementation of reperfusion therapy has resulted in increased survival and is currently the optimal treatment for acute MI. Death of cardiomyocytes following ischemia results in “danger signals” that elicit an inflammatory reaction that is crucial for removal of cell debris, wound healing, and generation of scar tissue. However, when the inflammatory response is excessive in duration and/or magnitude, it can result in exacerbated tissue damage and adverse remodeling contributing to the pathogenesis of heart failure. In order to successfully develop and implement inflammation modulating treatments that result in an optimal balance between healing, scar formation, and remodeling, visualization and characterization of the inflammatory response are crucial. Based on the imaging date, patient selection and precise targeting and timing of anti-inflammatory treatment can be realized. Various imaging techniques are under development and are being evaluated for this purpose. In this chapter we discuss the biology of post-MI inflammation and remodeling and relevant animal models and provide an overview of potentially promising imaging strategies.
... The aortic (ascending aorta, aortic arch, descending aorta) 18 F-NaF uptake was determined by manually placing oval ROIs on the equatorial plane of these major arteries to avoid artifacts from the accumulation of 18 F-NaF in the vertebral body [17]. The SUV max of 18 F-NaF avid focus more than 1.6 times the mean SUV of the right atrium blood pool was considered an abnormal aorta lesion. ...
... Pioneering studies demonstrated that the coronary 18 F-NaF uptake was signi cantly correlated with the CAC score and the progression of coronary calci cation [17,28]. Increased coronary 18 F-NaF uptake was associated with more rapid progression of coronary calci cation at one year in patients with clinically stable multivessel CAD [28]. ...
Purpose: ¹⁸F-Sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) is a novel approach to detect and quantify microcalcification in atherosclerosis. Peri-coronary adipose tissue (PCAT) is associated with vascular inflammation and high-risk atherosclerotic plaque. We aimed to assess the association between coronary ¹⁸F-NaF uptake with pro-atherosclerosis factors in patients with multivessel coronary artery disease (CAD) and to explore the systematic vascular osteogenesis in the coronary artery and aorta in these patients.
Methods: Patients with multivessel CAD prospectively underwent cardiac computed tomography (CT) and ¹⁸F-NaF PET/CT. PCAT density was measured in the coronary artery and the average PCAT value was calculated from the three coronary arteries in each patient. ¹⁸F-NaF tissue-to-blood ratios (TBR) in the coronary artery (TBRCoronary) and aorta (TBRAorta) were calculated. Correlations between coronary ¹⁸F-NaF uptake with PCAT density, coronary artery calcium (CAC) burden, CAD risk factors, serum biomarkers, and aortic ¹⁸F-NaF uptake were evaluated, respectively. Patients were categorized by a median of TBRCoronary 2.49.
Results: 100 multivessel CAD patients (64.00 [57.00 - 67.75] years; 76 men) were prospectively recruited. 6010 active aortic segments (TBR ≥ 1.6) were identified. TBRCoronary was significantly associated with the PCAT density (r = 0.56, p < 0.001) and CAC score (r = 0.45, p < 0.001). TBRCoronary was also significantly associated with the TBRAorta (r = 0.42, p < 0.001). In addition, patients with higher TBRCoronary showed elevated PCAT density (-75.89[-79.07 - -70.06] vs -84.54[-90.21 - -79.46]; p < 0.001) and CAC score (1495.20[619.80 - 2225.40] vs 273.75[116.73 - 1198.18]; p < 0.001) in comparsion patients with lower TBRCoronary. TBRCoronary was correlated with the age (r = 0.24, p = 0.019) and the serum troponin I levels (r = 0.22, p = 0.039). There were no significant correlations between TBRCoronary with other conventional CAD risk factors and other serum biomarkers.
Conclusion: Coronary ¹⁸F-NaF uptake was correlated with the PCAT density. A significant correlation between ¹⁸F-NaF uptake in the coronary artery and aorta might indicate a systematic vascular osteogenesis in patients with multivessel CAD.
... In a 19 oncologic patients experience, the NaF uptake measured as TBRmax, significantly increased from baseline (2.5 ± 0.8) to follow-up (2.8 ± 0.7, P < 0.05) with a corresponding increased calcium density increased [161]. Ishiwata et al. reported a significant correlation between baseline calcification vessel wall NaF uptake activity and the change after 1 year in terms of calcification volumetric score also as a predictor of future cardiovascular disease risk, in absence of new macrocalcification [162]. Further longitudinal studies are crucially needed to explore whether NaF accumulation precedes the development of overt arterial calcification, and to define the reproducibility and stability of NaF signal in coronary and carotid arteries, also in the coronary stenosis severity assessment (Fig. 4.7) [163]. ...
... but not with the changes in mean and maximum CT density. 9 Li et al. also reported a subsequent increase in both 18 F-NaF uptake and calcium CT density in atherosclerosis and found that most noncalcified lesions (86%) had concordant development of osteogenesis-derived 18 F-NaF uptake and inflammation-derived 18 F-FDG uptake. 10 Fiz et al.'s study has provided new evidence to support these previous findings. ...
... In a 19 oncologic patients experience, the NaF uptake measured as TBRmax, significantly increased from baseline (2.5 ± 0.8) to follow-up (2.8 ± 0.7, P < 0.05) with a corresponding increased calcium density increased [161]. Ishiwata et al. reported a significant correlation between baseline calcification vessel wall NaF uptake activity and the change after 1 year in terms of calcification volumetric score also as a predictor of future cardiovascular disease risk, in absence of new macrocalcification [162]. Further longitudinal studies are crucially needed to explore whether NaF accumulation precedes the development of overt arterial calcification, and to define the reproducibility and stability of NaF signal in coronary and carotid arteries, also in the coronary stenosis severity assessment (Fig. 4.7) [163]. ...
This book addresses the most relevant imaging techniques in order to detect inflammation and infection in the most common cardiovascular diseases. The book presents data concerning molecular imaging (SPECT and PET) and cardiac magnetic resonance imaging (MRI) for each disease, with a special focus on the emerging role of hybrid PET/MR imaging. Different non-ischemic and ischemic diseases as well as cardiac infections are addressed in detail; these include: Cardiac sarcoidosis, Cardiac amyloidosis, the vulnerable plaque, Post-infarction inflammatory alterations, Pericarditis, Myocarditis, Cardiac devices infections, and Endocarditis.
The book also provides a comprehensive discussion on new targets and new tracers, to date mostly investigated at a pre-clinical stage, thus constituting an excellent basis for translational imaging. Imaging of Inflammation and Infection in Cardiovascular Diseases will be of interest not only for experts in clinical imaging, but also pre-clinical scientists and will be invaluable for both nuclear medicine physicians and radiologists.
