Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors.

OBJECTIVES: There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. METHODS: In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). RESULTS: The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 - 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 - 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 - 0.23, p < 0.01), and LPA ( = -0.10, 95% CI -0.19 to -0.02, p=0.02) were independent associations of aSUVmax. CONCLUSIONS: Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects' risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. KEY POINTS: • Sodium fluoride ([18F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [18F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

A Critical Review of PET Tracers Used for Brain Tumor Imaging.

The brain is a common site for metastases as well as primary tumors. Although evaluation of these malignancies with contrast-enhanced MR imaging defines current clinical practice, 18F-fluorodeoxyglucose (FDG)-PET has shown considerable utility in this area. In addition, many other tracers targeting various aspects of tumor biology have been developed and tested. This article discusses recent developments in PET imaging and the anticipated role of FDG and other tracers in the assessment of brain tumors.

Novel Musculoskeletal and Orthopedic Applications of 18F-Sodium Fluoride PET.

PET imaging with 18F-sodium fluoride (NaF), combined with computed tomography or magnetic resonance, is a sensitive method of assessing bone turnover. Although NaF-PET is gaining popularity in detecting prostate cancer metastases to bone marrow, osseous changes represent secondary effects of cancer cell growth. PET tracers more appropriate for assessing prostate cancer metastases directly portray malignant activity and include 18F-fluciclovine and prostatic specific membrane antigen ligands. Recent studies investigating NaF-PET suggest utility in the assessment of benign musculoskeletal disorders. Emerging applications in assessing traumatic injuries, joint disease, back pain, orthopedic complications, and metabolic bone disease are discussed.

Non-18F-FDG/18F-NaF Radiotracers Proposed for the Diagnosis and Management of Diseases of the Heart and Vasculature.

18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) are front-runners in PET. However, these tracers have limitations in the imaging of diseases in the heart. A multitude of other radiotracers have been identified as potentially useful PET agents in the identification of cardiovascular disease. This critical review examines recent studies with the use of non-18F-FDG/18F-NaF radiotracers in the identification and surveillance of cardiovascular diseases. We highlight the need for further investigation into alternative PET radiotracers to demonstrate their clinical value in the management of these pathologies.

Global brain glucose uptake on 18F-FDG-PET/CT is influenced by chronic cardiovascular risk.

PURPOSE: The goal of this study was to assess global cerebral glucose uptake in subjects with known cardiovascular risk factors by employing a quantitative 18F-fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) technique. We hypothesized that at-risk subjects would demonstrate decreased global brain glucose uptake compared to healthy controls. METHODS: We compared 35 healthy male controls and 14 male subjects at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects were grouped into two age-matched cohorts: younger (<50 years) and older (≥50 years). The global standardized uptake value mean (Avg SUVmean) was measured by mapping regions of interest of the entire brain across the supratentorial structures and cerebellum. Wilcoxon's rank-sum test was used to assess the differences in Avg SUVmean between controls and at-risk subjects. RESULTS: Younger subjects demonstrated higher brain Avg SUVmean than older subjects. In addition, in both age strata, the 10-year risk for fatal CVD according to the SCORE tool was significantly greater in the at-risk groups than in healthy controls (younger: P = 0.0304; older: P = 0.0436). In the younger cohort, at-risk subjects demonstrated significantly lower brain Avg SUVmean than healthy controls (P = 0.0355). In the older cohort, at-risk subjects similarly had lower Avg SUVmean than controls (P = 0.0343). CONCLUSIONS: Global brain glucose uptake appears to be influenced by chronic cardiovascular risk factors. Therefore, FDG-PET/CT may play a role in determining the importance of CVD on brain function and has potential for monitoring the efficacy of various therapeutic interventions.

Venous thromboembolism detected by FDG-PET/CT in cancer patients: a common, yet life-threatening observation.

Cancer patients are at markedly increased risk for venous thromboembolism (VTE). Early detection of VTE may decrease morbidity and mortality in this population. We conducted this study to evaluate the ability of FDG-PET/CT to detect thrombosis in cancer patients. This retrospective study included 131 cancer patients with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) referred for 2-deoxy-2-[18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). All subjects underwent PET/CT imaging 60 minutes after FDG injection. Images were visually assessed for increased FDG uptake within the venous lumen. For positive cases, clinical follow-up and Doppler ultrasonography and/or contrast-enhanced CT scans were reviewed. FDG-PET/CT revealed abnormal uptake in the venous system of 26 (19.8%) patients. Eighteen (69.2%) had a history of DVT, and 13 (50%) had a history of PE. The most common site of thrombosis was the inferior vena cava (IVC) (n=14, 53.8%), followed by lower extremities veins (n=9, 34.6%), jugular veins (n=2, 7.7%), and superior vena cava (n=1, 3.8%). The presence of thrombi was confirmed by reviewing clinical follow-up in 6 (23.1%) patients. Among this group, thrombosis was detected in lower extremity veins (n=4, 15.8%), jugular veins (n=1, 3.8%), and IVC (n=1, 3.8%). Our study demonstrates that thrombi prior to their clinical manifestation can be detected by FDG-PET/CT in cancer patients. Moving forward, physicians must carefully consider the venous system when reporting FDG-PET/CT for cancer patients.

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

An Update on the Role of Total-Body PET Imaging in the Evaluation of Atherosclerosis.

Fused PET/computed tomography has demonstrated success in the detection and quantification of atherosclerotic plaques. Recently, total-body PET imaging has demonstrated increased sensitivity and specificity in atherosclerosis. This article reviews the literature regarding this novel imaging technique. Moreover, evidence that has pointed toward 18F-sodium fluoride as the radiotracer of choice over 18F-fluorodeoxyglucose for evaluation of plaque burden is discussed. Finally, a global disease assessment is introduced as an adjunct tool for vascular PET imaging.

18F-FDG-PET/CT in radiation therapy-induced parotid gland inflammation.

BACKGROUND: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used in the clinical management of oncologic and inflammatory pathologies. It may have utility in detecting radiotherapy (RT)-induced damage of oral tissues. Thus, the aim of the present study was to use FDG-PET/CT to evaluate parotid gland inflammation following RT in patients with head and neck cancer (HNC). METHODS: This retrospective study included patients with HNC treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received FDG-PET/CT imaging pre-treatment and 3 months post-treatment. The average mean standardized uptake value (Avg SUVmean) and the average maximum standardized uptake value (Avg SUVmax) of the left and right parotid glands were determined by global assessment of FDG activity using OsiriX MD software. A two-tailed paired t test was used to compare Avg SUVmean and Avg SUVmax pre- and post-RT. RESULTS: Forty-seven HNC patients were included in the study. Parotid gland Avg SUVmean was significantly higher at 3 months post-treatment than pre-treatment (p < 0.05) in patients treated with photon RT, but no significant differences were found between pre- and post-treatment Avg SUVmean in patients treated with proton RT or combined photon/proton RT. CONCLUSION: Our results suggest that photon RT may cause radiation-induced inflammation of the parotid gland, and that proton RT, which distributes less off-target radiation, is a safer treatment alternative.

PET/MR Imaging in Musculoskeletal Precision Imaging - Third wave after X-Ray and MR.

18F-Fluorodeoxyglucose PET has been used to evaluate a wide array of inflammatory and neoplastic pathologies. MR imaging has great soft tissue resolution and high accuracy for detection of edema. Combining PET with MR imaging offers substantial advantages in musculoskeletal imaging. Specifically, evidence demonstrates the potential of imaging of bone marrow, soft tissue, and synovia by PET/MR imaging. Because of inherent limitations of 1H-MR to image cortical bone, there are some challenges; however, the use of 18F-sodium fluoride for PET/MR imaging could change the landscape. This article reviews the literature regarding PET/MR imaging in identification and management of many musculoskeletal diseases.

Imaging Atherosclerosis by PET, With Emphasis on the Role of FDG and NaF as Potential Biomarkers for This Disorder.

Molecular imaging has emerged in the past few decades as a novel means to investigate atherosclerosis. From a pathophysiological perspective, atherosclerosis is characterized by microscopic inflammation and microcalcification that precede the characteristic plaque buildup in arterial walls detected by traditional assessment methods, including anatomic imaging modalities. These processes of inflammation and microcalcification are, therefore, prime targets for molecular detection of atherosclerotic disease burden. Imaging with positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) can non-invasively assess arterial inflammation and microcalcification, respectively. FDG uptake reflects glucose metabolism, which is particularly increased in atherosclerotic plaques retaining macrophages and undergoing hypoxic stress. By contrast, NaF uptake reflects the exchange of hydroxyl groups of hydroxyapatite crystals for fluoride producing fluorapatite, a key biochemical step in calcification of atherosclerotic plaque. Here we review the existing literature on FDG and NaF imaging and their respective values in investigating the progression of atherosclerotic disease. Based on the large volume of data that have been introduced to the literature and discussed in this review, it is clear that PET imaging will have a major role to play in assessing atherosclerosis in the major and coronary arteries. However, it is difficult to draw definitive conclusions on the potential role of FDG in investigating atherosclerosis given the vast number of studies with different designs, image acquisition methods, analyses, and interpretations. Our experience in this domain of research has suggested that NaF may be the tool of choice over FDG in assessing atherosclerosis, especially in the setting of coronary artery disease (CAD). Specifically, global NaF assessment appears to be superior in detecting plaques in tissues with high background FDG activity, such as the coronary arteries.

Utility of FDG-PET/CT in clinical psoriasis grading: the PET-PASI scoring system.

Psoriatic skin lesions are metabolically active, which makes them candidates for imaging with 18-F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The aim of our study was to correlate FDG-PET findings with Psoriasis Area and Severity Index (PASI) scores, the most widely-used grading system for psoriasis. Thirty-three subjects and a total of 84 FDG-PET/CT scans from a prospective clinical trial [NCT01553058] with >2 months moderate-to-severe psoriasis were included. Subjects underwent whole-body FDG-PET/CT imaging 60 min after intravenous FDG administration, prior to the start of treatment. Scans were repeated 12 weeks and 52 weeks after baseline scans were conducted and after treatment or placebo administration was initiated. Each subject and scan was graded by our "PET-PASI" scoring system, a qualitative review of multi-plane reconstructions for both attenuation-corrected (AC) and non-attenuation-corrected (NAC) PET images. PASI and PET-PASI scores were correlated using Spearman's rho analysis. Our study demonstrated a significant positive correlation between each subject's corresponding PET-PASI and PASI scores before and during treatment or placebo administration (r=0.53, P<0.001). We also found positive correlations between PET-PASI and PASI scores across different regions of the body (head and neck: r=0.22, upper extremities: r=0.26, trunk: r=0.48, and lower extremities: r=0.58). In conclusion, AC and NAC FDG-PET/CT images may be utilized to evaluate lesions in subjects with moderate-to-severe psoriasis. Our methodology could have future implications in the diagnosis and therapeutic management of psoriasis.

Applications of Hybrid PET/Magnetic Resonance Imaging in Central Nervous System Disorders.

PET with 18F-fluorodeoxyglucose (FDG) is used to assess a wide array of inflammatory and neoplastic disorders. FDG-PET has shown particular utility in the evaluation of disorders of the central nervous system (CNS). Although fused PET/computed tomography (CT) is frequently used across the globe for these diseases, recent evidence has pointed to PET/magnetic resonance (MR) imaging as a more sensitive and specific molecular imaging modality. This article reviews the literature regarding the advantages of PET/MR imaging compared with PET/CT imaging, especially in CNS disease. It also introduces a new concept for PET-based evaluation of patients with neurodegenerative disorders: global disease assessment.

Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

Pooled Cohort Equations (PCE) combines metabolic and non-metabolic parameters to predict the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Therefore, we hypothesize that ASCVD risk score is correlated to global cardiac microcalcification, as assessed by 18F-sodium fluoride-positron emission tomography/computed tomography (NaF-PET/CT). Sixty-one individuals (53.4±8.9 years, 32 females, 100% Caucasian) without known ASCVD underwent NaF-PET/CT imaging. Global cardiac average SUVmean (aSUVmean), also known as the Alavi-Carlsen Calcification Score, was calculated across manually defined regions of interest on each axial slice for each individual. The 10-year ASCVD risk score was determined for each individual using the PCE as per ACC/AHA guidelines, and then individuals were categorized into low-, borderline-, intermediate-, and high-risk groups based on their score. Linear regression analysis was applied to compare each individual's ASCVD score and aSUVmean. Global cardiac aSUVmean stratified by groups estimated by 10-year ASCVD risk score were 0.67±0.09 for low risk (n=32), 0.70±0.11 for borderline risk (n=10), 0.72±0.10 for intermediate risk (n=17), and 0.78±0.10 for high risk (n=2). ASCVD risk score was significantly correlated to aSUVmean (r=0.27, P=0.03). This is among the first studies to compare ASCVD risk scores to cardiac plaque burden as assessed by NaF-PET/CT. Large, prospective studies are needed to further investigate the potential of NaF uptake in ASCVD.

18F-FDG-PET/CT in the quantification of photon radiation therapy-induced vasculitis.

Radiation therapy (RT) is an important component of care for head and neck cancers (HNC). Photon RT vasculitis is a complication of incidental dose delivery to nearby vascular structures. However, optimal methods for early diagnosis are not clearly established. The aim of this study was to evaluate 18F-FDG-PET/CT in detecting radiation-induced vasculitis of the left common carotid (LCC) and the arch of the aorta (AoA) in patients treated for HNC. 18F-FDG-PET/CT scans obtained before RT (Pre-RT) and 3 months after RT (Post-RT) were retrospectively reviewed in 30 HNC patients (25 males, 5 females; average age 57.9±8.1 years) treated with photon RT. All subjects underwent 18F-FDG-PET/CT imaging 60 minutes after 5.0 MBq/kg 18F-FDG injection. Average standard uptake values (Avg SUVmean) of the LCC and AoA were obtained by global assessment. A two-tailed paired t-test was used to assess the difference in Avg SUVmean between pre- and post-RT imaging. Subjects demonstrated significant increased Avg SUVmean within the LCC post-RT (pre = 1.42, post = 1.65, P<0.001), with a mean increase of 0.23 SUV. Similarly, subjects exhibited higher 18F-FDG uptake in the AoA post-RT (pre = 1.44, post = 1.69, P<0.01), with a mean increase of 0.23 SUV. 18F-FDG-PET/CT may be used to detect and quantify photon RT vasculitis in HNC patients. Further investigation is warranted to evaluate the clinical implications of this pathology and the role for alternative treatment strategies in minimizing tissue toxicity.