Target-to-background Ratio Research Articles

Correlation of FDG PET/CT Findings with Long-Term Growth and Clinical Course of Abdominal Aortic Aneurysm.

Herein, we report characteristics of 18F-fluorodeoxyglucose (FDG) uptake in abdominal aortic aneurysms (AAAs) during a long-term follow-up. In addition, we investigated the association between FDG uptake and the physician decision to perform an intervention. We performed a retrospective review of 42 patients with AAAs who underwent FDG positron emission tomography (PET)/computed tomography (CT). The size of the AAA was measured in serial CT or PET/CT images. The long-term growth rate of AAAs was calculated by linear regression of the size change. Maximal SUV of the AAA (SUVAAA) and mean SUV of the blood pool (SUVBlood) were measured in PET/CT fusion images. To assess the FDG uptake of AAAs, the target-to-background ratio (TBR) was defined as the ratio of SUVAAA to SUVBlood. We compared FDG uptake of AAAs with the long-term growth rate of AAAs and clinical data. TBR was not significantly different between patients with and without significant growth (1.55±0.20 vs. 1.57±0.14; P=0.5599). However, in patients with significant growth, TBR exhibited a significant positive correlation with the growth rate (r2 =0.2601, P=0.0306). TBR also exhibited a significant difference between patients with and without intervention (P=0.0228). FDG uptake of AAA is associated with long-term growth of AAAs in a specified group that exhibits growth. FDG PET/CT may only be effective in predicting the long-term growth of AAAs in specific subgroups of patients. It is also suggested that FDG PET is potentially related to the clinical conditions of AAA patients who need surgical or interventional treatment.

TNF-α Antagonist and Vascular Inflammation in Patients with Psoriasis Vulgaris: A Randomized Placebo-Controlled Study

Vascular inflammation is increased in patients with psoriasis. This randomized, double-blind, multicenter study evaluated the effects of tumor necrosis factor-α antagonist adalimumab on vascular inflammation in patients with psoriasis. A total of 107 patients were randomized (1:1) to receive adalimumab for 52 weeks or placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography. There were no differences in the change from baseline in vessel wall target-to-background ratio (TBR) from the ascending aorta (primary endpoint) (adalimumab: TBR= 0.002, 95% confidence interval [CI]= -0.048 to 0.053; placebo: TBR= -0.002, 95% CI= -0.053 to 0.049; P= 0.916) and the carotids (adalimumab: TBR= 0.031, 95% CI= -0.005 to 0.066; placebo: TBR= 0.018, 95% CI= -0.019 to 0.055; P= 0.629) at week 16 between adalimumab and placebo. After 52 weeks of treatment with adalimumab there was no significant change from start of treatment in TBR from the ascending aorta (TBR= -0.006, 95% CI= -0.049 to 0.038; P= 0.796), but there was an increase in TBR in carotids (TBR= 0.027, 95% CI= 0.000 to 0.054; P= 0.046). This study showed no difference over 16 weeks in vascular inflammation in patients treated with a tumor necrosis factor-α antagonist or placebo and a modest increase in vascular inflammation in carotids after 52 weeks of treatment with adalimumab.

Near-infrared fluorescence laparoscopy of the cystic duct and cystic artery: first experience with two new preclinical dyes in a pig model

BackgroundImaging techniques that enhance visualisation of the anatomy may help prevent bile duct injury. Near-Infrared Fluorescence Imaging is such a technique. Previous experiments with ICG have shown that illumination of the extra-hepatic bile ducts is feasible. Yet, there is room for improvement in the visualisation of the target as compared to the background. Experiments with IRDye® 800CW show promising results. However, this dye is too expensive for routine clinical use. The aim of this study is to test the first applicability of two newly developed preclinical dyes regarding intraoperative imaging of the cystic duct and cystic artery, compared with IRDye® 800CW.MethodsLaparoscopic cholecystectomy was performed in three pigs, using a laparoscopic fluorescence imaging system. Each pig received 6 mg of one of the fluorescent dyes (1 mg/mL; IRDye® 800CW, IRDye® 800BK or IRDye® 800NOS) by intravenous injection. Intraoperative recognition of the biliary system and cystic artery was registered at set time points. All procedures were digitally recorded, and the target to background ratio (TBR) was determined to assess the fluorescence signal.ResultsWith all three fluorescent dyes, the cystic artery was directly visualised. For the visualisation of the cystic duct, 15, 34 and 30 min were needed using IRDye® 800BK, IRDye® 800NOS and IRDye® 800CW, respectively. The maximum TBR of the cystic duct was the highest with IRDye® 800NOS (4.20) after 36 min, compared to 2.45 for IRDye® 800BK and 2.15 for IRDye® 800CW, both after 45 min. There were no adverse events.ConclusionIRDye® 800BK and IRDye® 800NOS seem to be good alternatives for IRDye® 800CW for the visualisation of the cystic duct and cystic artery in pigs.

Characteristics of immunoglobulin G4-related aortitis/periaortitis and periarteritis on fluorodeoxyglucose positron emission tomography/computed tomography co-registered with contrast-enhanced computed tomography

BackgroundWe aimed to assess the positivity, distribution, quantitative degree of vessel inflammation, and clinical characteristics of IgG4-related aortitis/periarteritis and periarteritis (IgG4-aortitis), and to examine the difference in these characteristics between cases with and without IgG4-aortitis, using fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) co-registered with contrast-enhanced CT (CECT).We retrospectively evaluated 37 patients with IgG4-related disease (IgG4-RD) who underwent both FDG-PET/CT and CECT. The arterial SUVmax and its value normalized to the background venous blood pool (BP)—the target-to-background ratio (TBR) in the entire aorta and the major first branches—were measured. Active vascular inflammation was considered in cases with a higher FDG uptake than BP and a thickened arterial wall (>2 mm).ResultsFifteen (41%) patients exhibited IgG4-aortitis. Most patients (80%) showed multiple region involvement. The entire aorta, including the major first branches, were involved, typically showing a thickened wall and high FDG uptakes. The most common site was the iliac arteries (35%), followed by the infrarenal abdominal aorta (33%), thoracic aorta (8%), first branches of the thoracic aorta (8%), suprarenal abdominal aorta (6%), and the first branches of the abdominal aorta (5%). The IgG4-aortitis-positive vessel regions were thickened, with an average maximal wall thickness of 6.3 ± 2.9 mm. The SUVmax and TBR values were significantly higher in the IgG4-aortitis-positive regions (median 3.7 [1.6–5.5] and 2.1 [1.4–3.7], respectively) than in the IgG4-aortitis-negative regions (median 2.1 [1.2–3.7] and 1.3 [0.9–2.3], respectively; p < 0.0001). The IgG4-aortitis-positive group patients were older (69.5 ± 6.0 vs. 63.3 ± 12.6 years, respectively) and had a higher male predominance (80 vs. 55%, respectively) than the negative group, although the differences were not significant (p = 0.17 and p = 0.06, respectively).ConclusionsWe investigated the image characteristics of IgG4-aortitis. The entire aorta and major branches can be involved with more than 2-fold higher FDG uptake than the venous background pool, and with wall thickening. The most common involved site is the iliac arteries, followed by the infrarenal abdominal aorta.

Routine 18F-FDG PET/CT does not detect inflammation in the left atrium in patients with atrial fibrillation

Increasing evidence supports a role of inflammation in the development of atrial fibrillation (AF). However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce. In this study, we used 18-Fluor-Deoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) to determine atrial inflammation in patients with and without AF. Retrospectively, 18F-FDG PET/CT scans were analyzed. 37 patients with a history of AF were compared to an age and sex matched control group with no history of AF. Standardized uptake values were obtained in the atrial walls, in the left ventricular wall, and in the right ventricular blood pool, respectively. Target to background ratios (TBR) were determined in the atrial and left ventricular walls and compared between the two groups. TBR values of the left atrial wall were slightly but not significantly higher in patients with AF (1.21 ± 0.27) compared to those without AF (1.14 ± 0.29; p = 0.85). Likewise, a weak but not significant difference was observed in signal intensities in the right atrial wall between patients in the AF (1.14 ± 0.45) and the control group (0.96 ± 0.2; p = 0.41). TBR values of the left ventricular myocardium did not differ between the groups; no significant correlation was found between the TBR in the left and right atrial wall and blood glucose levels. 18F-FDG PET/CT performed under routine conditions did not detect a significant difference in inflammatory activity in the left or right atrium between patients with and without AF. Contrary to previous reports, these results therefore do not clearly support a role for ongoing atrial inflammation in patients with AF. Prospective clinical studies using myocardial glucose uptake suppression strategies may be helpful to clarify these issues.

Abstract WP422: 18 F-FDG PET/CT Imaging Factors for Prediction of Ischemic Stroke in Cancer Patients

Objective: 18 F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of 18 F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischemic stroke in cancer patients. Methods: One hundred and thirty-four cancer patients were enrolled. A new infarct lesion in brain MRI within 1 year after FDG PET/CT defined future ischemic stroke. A target-to-background ratio (TBR) for each arterial segment defined arterial inflammation on PET imaging. Abdominal obesity was defined as area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT), on a single CT slice at the umbilical level. Results: Thirty patients experienced the occurrence of future ischemic stroke confirmed by MRI. Patients who suffered a stroke had TBRs in carotid arteries and the abdominal aorta ( P &lt;0.001) that were higher than those in patients without stroke. Patients with stroke had higher VAT ( P =0.021) and TAT ( P= 0.041) proportions than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and metabolically active tumors were significantly associated with future ischemic stroke. The combination of PET and CT variables improved predictive power for future ischemic stroke. Conclusion: Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET, and VAT proportion on CT, could be independent predictors of future ischemic stroke in patients with cancer and identify those patients who would benefit from medical treatment.

18F-FDG positron emission tomography/computed tomography in infective endocarditis

BackgroundThe diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in IE. MethodsSixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference. ResultsThere was strong, focal 18F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUVmax of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE. Conclusions18F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Diagnostic Value of 68Ga PSMA-11 PET/CT Imaging of Brain Tumors-Preliminary Analysis.

To evaluate the feasibility of using Ga PSMA-11 PET/CT for imaging brain lesions and its comparison with F-FDG. Ten patients with brain lesions were included in the study. Five patients were treated cases of glioblastoma with suspected recurrence. F-FDG and Ga PSMA-11 brain scans were done for these patients. Five patients were sent for assessing the nature (primary lesion/metastasis) of space occupying lesion in brain. They underwent whole body F-FDG PET/CT scan and a primary site elsewhere in the body was ruled out. Subsequently they underwent Ga PSMA-11 brain PET/CT imaging. Target to background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. In five treated cases of glioblastoma with suspected recurrence the findings of Ga PSMA-11 PET/CT showed good correlation with that of F-FDG PET/CT scan. Compared to the F-FDG, Ga PSMA-11 PET/CT showed better visualization of the recurrent lesion (presence/absence) owing to its significantly high TBR. Among the five cases evaluated for lesion characterization glioma and atypical meningioma patients showed higher SUVmax in the lesion with Ga PSMA-11 than with F-FDG and converse in cases of lymphoma. TBR was better with Ga PSMA PET/CT in all cases. Ga PSMA-11 PET/CT brain imaging is a potentially useful imaging tool in the evaluation of brain lesions. Absence of physiological uptake of Ga PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of metabolically active disease in brain.

Association between active brown adipose tissue and coronary artery calcification in healthy men.

We compared various clinical factors between persons with active brown adipose tissue (ABAT) and matched controls, and investigated the relationship between the presence of ABAT and coronary artery calcification (CAC) with respect to arterial inflammation. We retrospectively reviewed fluorine-18-labeled fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) data from men who underwent general health check-ups. Sixty-seven men with ABAT were identified and were matched with controls at a 1:1 ratio. Peripheral blood samples were obtained and the levels of various laboratory parameters were measured just before FDG PET/CT studies. Arterial inflammation was measured in the ascending aorta, venous mean standardized uptake value (SUV) was collected from the superior vena cava as FDG uptake on PET, and background-corrected SUV was calculated as the target-to-background ratio (TBR) and blood-subtracted SUVmax (bsSUVmax). CAC was assessed using CT images acquired from a PET/CT scanner. The prevalence of fatty liver (p = 0.048) and CAC (p = 0.026) was lower in men with ABAT compared to matched controls. Arterial SUVmax (1.72 ± 0.23 vs. 1.88 ± 0.23, p < 0.001), TBR (1.18 ± 0.14 vs. 1.29 ± 0.13, p < 0.001), and bsSUVmax (0.25 ± 0.18 vs. 0.41 ± 0.16, p < 0.001) were significantly lower in men with ABAT. ABAT (odds ratio [OR] = 0.19, p = 0.024) and high-density lipoprotein cholesterol (OR = 0.95, p = 0.037) were independent factors associated with CAC according to multiple logistic regression analysis. ABAT is associated with down-regulated arterial inflammation and may exert a protective effect against the development of atherosclerosis. (p = 0,026) war geringer bei Männern mit ABAT im Vergleich zu gematchten Kontrollen. Arterieller SUVmax (1,72 ± 0,23 vs. 1,88 ± 0,23, p < 0,001), TBR (1,18 ± 0,14 vs. 1,29 ± 0,13, p < 0,001) und bsSUVmax (0,25 ± 0,18 vs. 0,41 ± 0,16, p < 0,001) waren bei Männern mit ABAT signifikant geringer. ABAT (Odds ratio [OR] = 0,19, p = 0,024) und HDL-Cholesterol (OR = 0,95, p = 0,037) waren in einer multiplen logistischen Regressionsanalyse unabhängige Faktoren, die mit CAC assoziiert waren. Schlussfolgerung : ABAT ist assoziiert mit einer herunterregulierten arteriellen Entzündung und übt möglicherweise einen schützenden Effekt gegen die Entwicklung einer Atherosklerose aus.

Inflamed human carotid plaques evaluated by PET/CT exhibit increased temperature: insights from an in vivo study.

To explore the relationship between temperature measurements derived by microwave radiometry (MWR) and carotid flurodeoxyglucose (FDG) uptake and assess their association with histological and immunohistochemistry findings in patients with high-grade carotid stenosis. In 21 patients undergoing carotid endarterectomy, carotid inflammation was evaluated by both FDG positron emission/computed tomography (FDG-PET/CT) imaging and MWR measurements. Carotid inflammation was assessed by PET/CT as target-to-background ratio (TBR) by obtaining measurements in consecutive axial slices 2 cm below to 2 cm above the carotid bifurcation. Temperature difference (ΔT) by MWR was assigned as the maximum-minimum temperature measurements over the corresponding carotid segments. The extent of lipid core, calcification as well as CD68 and CD31 levels were also assessed. There was a significant correlation between ΔT values and FDG uptake (R = 0.40, P = 0.01), but no correlation between the degree of angiographic stenosis and ΔT values (R = -0.02, P = 0.91) or PET/CT measurements (R = -0.28, P = 0.86). Patients with plaques containing high lipid core extension or low calcification exhibited higher ΔT (P = 0.001 and P < 0.001, respectively) and FDG uptake values (P = 0.02 and P = 0.02, respectively). Patients with plaques containing increased CD68 expression exhibited higher ΔT and FDG uptake measurements. Carotid plaque inflammation was evaluated by temperature measurements, which were correlated with FDG-PET/CT indices, confirmed by histopathology and immunohistochemistry findings. Structural changes did not predict inflammatory process. The implications of these findings in risk stratification and management of patients with carotid atherosclerosis and the precise algorithm for potential clinical utilization of MWR and PET/CT remain to be determined.

Carotid arterial wall inflammation in peripheral artery disease is augmented by type 2 diabetes: a cross-sectional study.

BackgroundPatients with peripheral artery disease (PAD) are at increased risk of secondary events, which is exaggerated in the presence of type 2 diabetes mellitus. Diabetes is associated with a systemic pro-inflammatory state. We therefore investigated the cumulative impact of PAD and type 2 diabetes on carotid arterial wall inflammation. As recent data suggest a detrimental role of exogenous insulin on cardiovascular disease, we also included a group of insulin users.Results 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) imaging showed increased carotid arterial wall inflammation, assessed as target-to-background ratio (TBR), in PAD patients without diabetes (PAD-only: n = 11, 1.97 ± 0.57) compared with matched controls (n = 12, 1.49 ± 0.57; p = 0.009), with a significant further TBR increase in PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 ± 1, p = 0.033 vs PAD-only). TBR of insulin users (n = 12, 3.31 ± 1.14) was higher compared with patients on oral medication only (n = 11, 2.44 ± 0.76, p = 0.035), despite comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous insulin, correlated with TBR.ConclusionsConcurrent diabetes significantly augments carotid arterial wall inflammation in PAD patients. A further increase in those requiring insulin was observed, which was associated with diabetes severity, rather than with the use of exogenous insulin itself.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0397-x) contains supplementary material, which is available to authorized users.

Abstract 12607: Improvement in Skin Inflammation Associates With Improvement in Aortic Vascular Inflammation by 18-FDG PET/CT in Psoriasis

Introduction: Inflammation is a risk factor for the initiation and progression of atherosclerosis. Psoriasis (PSO), a chronic inflammatory skin disease, is an emerging risk factor for cardiovascular (CV) disease. Indeed PSO severity is associated with increased vascular inflammation (VI) by 18-FDG PET/CT in vivo and with future CV risk. However, the longitudinal impact of changes in PSO severity on vascular disease is unknown. Hypothesis: We hypothesized that an improvement in PSO severity would associate with an improvement in VI by FDG PET/CT. Methods: Consecutively recruited PSO patients (N=102) underwent FDG PET/CT scans, and cardiometabolic profiling at baseline and 1-year. VI was assessed as target-to-background ratio (TBR) (Excellence Brilliant Workstation). PSO severity was measured as Psoriasis Area Severity Index (PASI) score. The longitudinal change in VI of the aortic arch was analyzed using unadjusted and adjusted multivariable regression. Results: The cohort was middle-aged, had a low CV risk by Framingham risk score and had mild to moderate PSO severity. At follow-up, patients had a median improvement in PASI score of 31.91% (p&lt;0.001) with use of topical (67%), biological (62%) and UVB (16%) therapy. Aortic TBR in these patients improved (6.3%, p&lt;0.001) (Table 1). Improvement in PASI score associated with an improvement in aortic arch TBR beyond adjustment for traditional CV risk factors, statin use, &amp; systemic/biologic PSO therapy (β=0.21, p = 0.03). Conclusions: Improvement in PSO severity associated with an improvement in aortic VI by FDG PET/CT, suggesting that skin inflammation may present a modifiable risk factor to mitigate CV risk. This finding of a 6.3% decrease in VI with improvement in PASI score is of similar magnitude to that observed after low-dose statin therapy in coronary artery disease, suggesting control of remote inflammation may quell vascular disease progression. Larger studies are needed to confirm these findings.

Abstract 12593: Improvement in Aortic Vascular Inflammation by 18-FDG PET/CT Associates With Reduction in Aortic Wall Thickness by MRI

Introduction: The presence of aortic vascular inflammation (VI) by 18-FDG PET/CT predicts future cardiovascular (CV) events. Furthermore, aortic wall thickness by MRI has been shown to be an important marker of early subclinical atherosclerosis. Whether improvement in aortic vascular inflammation by FDG PET/CT is associated with improvement in aortic wall thickness by MRI is not known. Hypothesis: We hypothesized that an improvement in VI by FDG PET/CT will associate with an improvement in aortic wall thickness by MRI in a well characterized cohort of Psoriasis (PSO) patients. Methods: Consecutively recruited PSO patients (N=64) underwent whole-body PET/CT and MRI exams at baseline and 1-year follow-up. VI was assessed as target-to-background ratio (TBR) [Excellence Brilliant Workstation]. To measure aortic wall thickness, wall boundaries of the thoracic descending aorta were traced on each MRI slice [Qplaque, Medis]. The longitudinal change in wall thickness of the thoracic descending aorta was analyzed using unadjusted and adjusted multivariable regression (STATA 12). Results: The cohort was middle-aged (mean±SEM 50.67±1.80) and had a low cardiovascular risk by Framingham risk score [median-3, IQR- (1-7)]. Overall the cohort had an average TBR of 1.74±0.02 consistent with moderate vascular inflammation. At follow-up, the total cohort had a mean improvement in TBR of 7.47% (p&lt;0.001) with use of topical therapy (64%), biological therapy (59%) and UVB (13%). Improvement in TBR of the aorta was associated with reduction in mean wall thickness of the descending thoracic aorta beyond adjustment for traditional risk factors, statin use, &amp; systemic/biologic PSO therapy (β=0.30, p = 0.03). Conclusions: Improvement in aortic VI by FDG PET/CT was associated with reduction in aortic wall thickness by MRI at one year, suggesting a reduction in VI may improve early atherosclerosis. Our findings suggest that an improvement in vascular inflammation may mitigate structural abnormalities of the aorta. Randomized controlled studies are needed to confirm these findings.

Arterial and Cellular Inflammation in Patients with CKD.

CKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes. We assessed 18F-FDG uptake in the arterial wall in 14 patients with CKD (mean±SD age: 59±5 years, mean±SD eGFR: 37±12 ml/min per 1.73 m2) but without cardiovascular diseases, diabetes, or inflammatory conditions and in 14 control subjects (mean age: 60±11 years, mean eGFR: 86±16 ml/min per 1.73 m2). Compared with controls, patients with CKD showed increased arterial inflammation, quantified as target-to-background ratio (TBR) in the aorta (TBRmax: CKD, 3.14±0.70 versus control, 2.12±0.27; P=0.001) and the carotid arteries (TBRmax: CKD, 2.45±0.65 versus control, 1.66±0.27; P<0.001). Characterization of circulating monocytes using flow cytometry revealed increased chemokine receptor expression and enhanced transendothelial migration capacity in patients with CKD compared with controls. In conclusion, this increased arterial wall inflammation, observed in patients with CKD but without overt atherosclerotic disease and with few traditional risk factors, may contribute to the increased cardiovascular risk associated with CKD. The concomitant elevation of monocyte activity may provide novel therapeutic targets for attenuating this inflammation and thereby preventing CKD-associated cardiovascular disease.

Clinical Significance of Pretreatment FDG PET/CT in MIBG-Avid Pediatric Neuroblastoma.

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information-including histopathology, and serum markers-and several PET parameters-including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)-were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Total 20 patients (4.5 ± 3.5years) were divided as two groups by disease progression. Six patients (30.0%) experienced disease progression and one patient (5.0%) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

COMPARISON OF THE TWO METHODS FOR THE VASCULAR INFLAMMATION USING FDG PET/CT OF THE AORTA

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a state-of-the-art imaging technique that assesses inflammatory activity in the aorta. The current standard methodology involves quantification of FDG uptake on every 4-8 mm cross-sectional slices of three aortic regions (ascending, arch and descending). The resulting FDG standard uptake values (SUVs) for each slice within each aortic region are averaged and corrected for blood background activity to obtain a target-to background ratio (TBR) for the mean and maximal values of each aortic region of interest. On average, this method calls for over 100 slices to be traced for total aortic quantification. This methodology is time-consuming and cumbersome. We developed a simpler methodology in which each aortic region of interest is traced only twice longitudinally, SUVs averaged, and TBR values computed (fig). This new, less laborious methodology would greatly facilitate large-scale studies using FDG-PET/CT. In this study we aimed at a) testing the correlation between the new method of quantifying vascular inflammation using FDG-PET/CT and the current standard method; and b) testing the reproducibility of the new method.

Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging: Implications for Vascular Interventional Studies

ObjectivesThis study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies. Background18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available. Methods18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results. ResultsAll 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta. ConclusionsWe report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006)

18F-FDG PET/CT imaging factors that predict ischaemic stroke in cancer patients.

18F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of 18F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischaemic stroke in cancer patients. From among cancer patients presenting with various neurological symptoms and hemiparesis, 134 were selected as eligible for this retrospective analysis. A new infarct lesion on brain MRI within 1year of FDG PET/CT defined future ischaemic stroke. The target-to-background ratio (TBR) of each arterial segment was used to define arterial inflammation on PET imaging. Abdominal obesity was defined in terms of the area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT) on a single CT slice at the umbilical level. Ischaemic stroke confirmed by MRI occurred in 30 patients. Patients with stroke had higher TBRs in the carotid arteries and abdominal aorta (P < 0.001) and a higher VAT proportion (P = 0.021) and TAT proportion (P = 0.041) than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and the presence of a metabolically active tumour were significantly associated with future ischaemic stroke. Combining PET and CT variables improved the power for predicting future ischaemic stroke. Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET and the VAT proportion on CT could be independent predictors of future ischaemic stroke in patients with cancer and could identify those patients who would benefit from medical treatment.

Whole-body direct 4D parametric PET imaging employing nested generalized Patlak expectation–maximization reconstruction

Whole-body (WB) dynamic PET has recently demonstrated its potential in translating the quantitative benefits of parametric imaging to the clinic. Post-reconstruction standard Patlak (sPatlak) WB graphical analysis utilizes multi-bed multi-pass PET acquisition to produce quantitative WB images of the tracer influx rate Ki as a complimentary metric to the semi-quantitative standardized uptake value (SUV). The resulting Ki images may suffer from high noise due to the need for short acquisition frames. Meanwhile, a generalized Patlak (gPatlak) WB post-reconstruction method had been suggested to limit Ki bias of sPatlak analysis at regions with non-negligible 18F-FDG uptake reversibility; however, gPatlak analysis is non-linear and thus can further amplify noise. In the present study, we implemented, within the open-source software for tomographic image reconstruction platform, a clinically adoptable 4D WB reconstruction framework enabling efficient estimation of sPatlak and gPatlak images directly from dynamic multi-bed PET raw data with substantial noise reduction. Furthermore, we employed the optimization transfer methodology to accelerate 4D expectation–maximization (EM) convergence by nesting the fast image-based estimation of Patlak parameters within each iteration cycle of the slower projection-based estimation of dynamic PET images. The novel gPatlak 4D method was initialized from an optimized set of sPatlak ML-EM iterations to facilitate EM convergence. Initially, realistic simulations were conducted utilizing published 18F-FDG kinetic parameters coupled with the XCAT phantom. Quantitative analyses illustrated enhanced Ki target-to-background ratio (TBR) and especially contrast-to-noise ratio (CNR) performance for the 4D versus the indirect methods and static SUV. Furthermore, considerable convergence acceleration was observed for the nested algorithms involving 10–20 sub-iterations. Moreover, systematic reduction in Ki % bias and improved TBR were observed for gPatlak versus sPatlak. Finally, validation on clinical WB dynamic data demonstrated the clinical feasibility and superior Ki CNR performance for the proposed 4D framework compared to indirect Patlak and SUV imaging.

Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes.

Type 2 diabetes is accompanied by premature atherosclerosis and arterial stiffness. The underlying association remains incompletely understood. The possible relationship between subclinical arterial inflammation assessed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and arterial stiffness was investigated in patients with early type 2 diabetes. Patients with type 2 diabetes (n = 44), without cardiovascular disease and any type of antidiabetic medication, were studied (median age 63 years [interquartile range 54-66], men:women 27:17). Arterial inflammation was quantified as the FDG uptake maximal standardized uptake value (SUVmax). SUVmax was corrected for the prescan glucose level. A target-to-background ratio (TBR) was calculated by dividing the SUVmax of the arteries by the SUVmean of the caval veins (blood pool). TBRs were calculated for four individual segments (carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries) and averaged for the total aortic tree (meanTBR). Arterial stiffness was assessed as central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (PWV), and augmentation index (AIx). The meanTBR was significantly associated with PWV (R = 0.47, P = 0.001) and cSBP (R = 0.45, P = 0.003) but not with AIx. TBR of each separate segment was also significantly associated with PWV and cSBP. In a multiple linear regression model including age, sex, BMI, hemoglobin A1c (HbA1c), hs-CRP, cholesterol, cSBP, and PWV, PWV was the strongest determinant of meanTBR. In patients with type 2 diabetes, FDG-PET/CT-imaged subclinical arterial inflammation is positively associated with determinants of arterial stiffness.