Target-to-background Ratio Research Articles

Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial

BackgroundInflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation. MethodsThis phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements. ResultsThe mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, −0.70 to −0.36, P < 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P < 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P < 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, −8.6 to −4.5, P < 0.001) and 9.6% (95% CI, −24.5 to −5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month. ConclusionsSDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD. Trial registrationClinical Trials NCT03457662.

Two-hour postload plasma glucose and pigment epithelium-derived factor levels are markers of coronary artery inflammation in type 2 diabetic patients

BackgroundWe have previously found that pioglitazone attenuates inflammation in the left main trunk of coronary artery (LMT), evaluated as target-to-background ratio (TBR) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with impaired glucose tolerance or type 2 diabetes. ObjectivesWe assessed which clinical variables could predict the change in TBR in the LMT after 4-month add-on therapy with oral hypoglycemic agents (OHAs). MethodsA total of 38 type 2 diabetic patients with carotid atherosclerosis who had already received OHAs except for pioglitazone was enrolled. At baseline and 4 months after add-on therapy with pioglitazone or glimepiride, all patients underwent 75 g oral glucose tolerance test, blood chemistry analysis, and FDG-PET/CT. ResultsFasting plasma glucose, 30-, 60-, 90-, 120-minutes postload plasma glucose, HbA1c, and LMT-TBR values were significantly decreased by add-on therapy, whereas high-density lipoprotein-cholesterol and adiponectin levels were increased. Increased serum levels of pigment epithelium-derived factor (PEDF), a marker of insulin resistance and non-use of aspirin at baseline could predict the favorable response of LMT-TBR to add-on therapy. Moreover, Δ120-minutes postload plasma glucose and ΔPEDF were independent correlates of ΔLMT-TBR. ConclusionsOur present study suggests that 120-minutes postload plasma glucose and PEDF values may be markers and potential therapeutic targets of coronary artery inflammation in type 2 diabetic patients. Clinical Trial RegistrationURL: http://clinicaltrials.gov. Unique identifier: NCT00722631. Graphic AbstractNew markers for diabetes and CAD is on the horizon! Two-hour postload plasma glucose and pigment epithelium derived factor are markers of coronary artery inflammation in type 2 diabetic patients.▪

A Preliminary 18F-FDG-PET/MRI Study Shows Increased Vascular Inflammation in Moderate-to-Severe Atopic Dermatitis

Recent data suggest that patients with atopic dermatitis (AD) have increased systemic immune activation and cardiovascular risk. However, unlike psoriasis, evaluation of active vascular inflammation using state-of-the-art imaging is lacking in AD. To assess aortic and carotid vascular inflammation using 18F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (18F-FDG-PET/MRI) imaging in moderate-to-severe AD versus healthy individuals. A total of 27 patients with moderate-to-severe AD and 12 healthy controls were imaged using 18F-FDG-PET/MRI. Target-to-background ratio (TBR) values were calculated in multiple segments of the aorta and carotid vessels. Patients with AD had elevated aortic max TBR (fold change [FCH]= 1.45, P= .057) versus healthy controls and significantly elevated mean TBR (FCH= 1.20; P < .05) in the right carotid (RC) arteries versus controls. When examining greatest focal inflammation (most diseased segment [MDS] TBR), patients with AD had higher aortic inflammation (FCH= 1.28; P= .052). AD clinical severity significantly correlated with C-reactive protein (ρ= 0.60, P < .01) and with RC mean TBR levels (ρ= 0.60, P= .04). Stratifying patients into moderate-to-severe and very severe AD showed greater RC mean TBR in patients with very severe AD versus controls (FCH= 1.31; P= .02) and versus patients with moderate/severe AD (FCH= 1.23, P= .05). Aortic inflammation was also significantly greater in patients with very severe AD versus controls (max TBR: FCH= 1.6, P=.04; MDS TBR: FCH= 1.73, P= .03). This preliminary study is the first that establishes greater vascular (aorta and carotid) inflammation in moderate-to-severe AD versus healthy controls. Furthermore, very severe AD showed higher inflammation than both moderate/severe patients and healthy controls. Future studies with larger patient cohorts and evaluation before and after treatment are needed to determine the extent to which vascular inflammation in AD is modifiable.

Noninvasive Near-Infrared Fluorescence Imaging of the Ureter During Robotic Surgery: A Demonstration in a Porcine Model.

Background: Iatrogenic ureteral injury is one of the feared complications during intrapelvic surgery. There are limited data on the use of novel near-infrared fluorescence (NIRF) imaging dyes for the purpose of noninvasive ureteral visualization in robot-assisted laparoscopic surgery (RALS). In this study, we evaluated the feasibility of NIRF imaging of the ureter using the IRDye® 800BK dye as the fluorescence dye and a robotic platform with Firefly™ technology as an imaging system. Materials and Methods: An intravenous dose of 0.15 mg/kg was administered in 3 pigs and NIRF imaging was performed for a total duration of 60 minutes. The intraoperative video recordings were analyzed to determine fluorescence intensities and the target-to-background ratio (TBR). Results: In all included animals, a clear delineation of the ureter was achieved from 5 minutes after dye administration until the end of the study. During this time period, the ureter was clearly distinguishable from its surroundings and no statistical differences in TBR were observed. Conclusion: The IRDye 800BK dye, a novel NIRF dye currently undergoing clinical translation, is a promising contrast agent used for noninvasive ureteral imaging, which has the potential to be valuable during RALS.

Detection of sub-centimeter lesions using digital TOF-PET/CT system combined with Bayesian penalized likelihood reconstruction algorithm.

Many advances in PET/CT technology can potentially improve image quality and the ability to detect small lesions. A new digital TOF-PET/CT scanner based on silicon photomultipliers (SiPM) integrated with a Bayesian penalized likelihood (BPL) PET reconstruction algorithm (Q.Clear; GE Healthcare) has been introduced into clinical practice. The present study aimed to quantify the ability of a digital TOF-PET/CT scanner combined with BPL reconstruction to detect small lesions, and to determine the optimal penalization factor (β) in BPL to accurately detect such lesions. All PET data were acquired from a NEMA body phantom using a Discovery MI (DMI) PET/CT system (GE Healthcare). The phantom included six spheres with diameters of 4, 5, 6, 8, 10, and 13mm, and contained a background activity level of 5.3kBq/mL, with target-to-background ratios (TBR) of 4:1 and 8:1. Images were reconstructed using a baseline OSEM algorithm, with OSEM + PSF, OSEM + TOF, OSEM + PSF + TOF, and BPL + PSF + TOF (β: 50-400). The matrix size was 192 × 192 and 384 × 384. Data acquired in 100-min list mode were re-binned into acquisition times ranging from 2 to 100min. The quantitative accuracy and detectability of small hot spheres were evaluated by physical assessment of a recovery coefficient (RC) and a detectability index (DI), as well as visual assessment of PET images at each acquisition time. The RC and DI of sub-centimeter spheres were improved, because the digital TOF-PET/CT scanner has a larger TOF performance gain due to better timing resolution. The RC and DI were higher with BPL in sub-centimeter spheres, than with other OSEM-based types of reconstruction. The BPL for an 8-mm sphere overestimated uptake due to edge artifact overshoot induced by PSF modeling. The variability of RC and DI for acquisition times and TBR differed considerably according to β values. The RC for ~ 8-mm spheres were > 1 at β values between 50 and 100, but were close to 1 at β value of 200. The visual scores for β = 200 in BPL were maximal, whereas those for spheres that were ≥ 6mm exceeded the criterion of 3. The BPL in the digital TOF-PET/CT scanner improved the quantitation and detectability of sub-centimeter spheres compared with OSEM-based reconstruction. Optimization of the β value in BPL might allow the detection of lesions ≤ 6mm, although detectability depended on the TBR of lesions. A β value of 200 seemed optimal for detecting sub-centimeter lesions.

18F-FDG uptake as a predictive factor for progressive aortic enlargement in aortic dissection.

Progressive aortic enlargement (PAE) is a critical adverse event in patients with medically treated aortic dissection (AD). However, no reliable predictor of the PAE has been established. The purpose of this study was to evaluate the value of 18F-FDG PET/CT for the prediction of PAE in patients with medically treated AD. Sixteen patients with AD who underwent optimal medical therapy were enrolled. 18F-FDG PET/CT examinations were performed in subacute phase (2weeks-3months) after the onset of AD. Target-to-background ratio (TBR) was measured as the maximum standardized uptake value (SUV) in the dissected aortic wall divided by blood pool SUV. The relation between TBR and occurrence of PAE (> 10mm/year) was evaluated. PAE was observed in four patients during the median follow-up period of 24months. The TBR measured in the 4 patients showing PAE was significantly higher than that in the remaining 12 patients without PAE (2.44 ± 0.56 vs 1.87 ± 0.33, P = 0.025). The area under the receiver operating characteristic curve of TBR for predicting PAE was 0.82. With a threshold of 2.34, the TBR showed the sensitivity, specificity, and positive and negative predictive value of 75%, 92%, 75%, and 92%, respectively, for the prediction of PAE. Higher 18F-FDG uptake in the dissected aortic wall as determined by TBR is associated with increased risk of PAE in patients with medically treated AD. TBR shows good specificity and negative predictive value for predicting PAE.

Accuracy of metabolic volume and total glycolysis among six threshold-based target segmentation algorithms.

This study aimed to evaluate the accuracy of six threshold-based segmentation methods with different target-to-background ratios (TBR), images with different voxel sizes and image noise, in measuring metabolic volume (MV) and total glycolysis (TG). A standard body phantom consisting of six spheres (inner diameters of 37, 28, 22, 17, 13, and 10mm) was filled with 18F-FDG solution. The background radioactivity level was 2.65kBq/mL, and the TBRs were 4 and 8. PET data were acquired for 30min with list mode. PET data for 30 and 3min were reconstructed with a three-dimensional ordered subset expectation maximization algorithm plus time-of-flight information with images with 2 and 4mm isotropic voxels. The six methods examined were absolute standardized uptake value (SUV) of 2.5 (SUV2.5), 41%, 50%, adaptive 41%, and adaptive 50% thresholds of maximum SUV (Th41, Th50, ThA41, and ThA50, respectively); and the contrast-oriented algorithm (ThCOA). Segmented MV and TG were compared with the actual inner volume and expressed as percentages (%MVseg and %TGseg, respectively). In addition, the segmented MV was converted to the diameter, and the differences of it from the reference diameter were compared among six methods. The ThCOA method yielded the most accurate measurements of %MVseg and %TGseg; the difference between %MVseg or %TGseg and its reference were smaller than 10% in 30-min and 15% in 3-min images, but the segmented contour was almost the same as the reference diameter. Measurements with Th50 and ThCOA were highly accurate for both %MVseg and %TGseg in the large spheres, and the adaptive threshold methods, including ThA41, ThA50, and ThCOA, were also highly accurate in the small spheres. The voxel sizes affected the accuracy of %MVseg and %TGseg with a TBR of 4 in any threshold-based methods. Of the six threshold-based segmentation methods studied, ThCOA was the most accurate method for evaluating MV and TG and had only minor dependence on TBRs and sphere size. The small voxel sizes improved the variation of the accuracy in low TBR.

Fibroblast imaging of hepatic carcinoma with 68Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules.

68Ga-FAPI-04 is a rapidly evolving PET tracer for whole-body imaging in a variety of cancers. We aimed to evaluate the diagnostic performance of 68Ga-FAPI-04 for detecting and characterizing hepatic nodules in patients with suspected carcinoma. Twenty-five patients showing suspicious hepatic lesions for malignancy underwent 68Ga-FAPI-04 PET. The maximum and mean standardised uptake values (SUVmax, SUVmean) were measured for all detected lesions and normal hepatic tissues, respectively. The target-to-background ratio (TBR) was calculated by dividing the lesion SUVmax with the SUVmean of non-tumour liver tissue. Lesion uptake value was correlated with the in vitro hepatic FAP expression determined by immunohistochemistry (IHC). In total, 17 patients who underwent surgery or biopsy were recruited for the final analysis. A total of 28 intrahepatic malignant lesions were detected in 16 patients; the mean SUVmax was 8.36 ± 4.21 (range 2.21 to 15.86), and mean TBR was 13.15 ± 9.48 (range 2.79 to 38.12) in all detected lesions (n= 28). One benign patient showed negligible hepatic uptake (SUVmax= 0.47), whereas 75% of the primary intrahepatic hepatocellular carcinoma (HCC) lesions (n= 6) showed prominent FAP expression, 12.5% of the lesions (n= 1) showed moderate expression in stromal cells, and one showed negligible expression. 68Ga-FAPI-04 showed high sensitivity in detecting hepatic malignancies, particularly in poorly differentiated forms with concordantly elevated FAP expression.

Skin and Arterial Wall Deposits of 18F-NaF and Severity of Disease in Patients with Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by the calcification of elastin fibers. Our aim was to quantify vascular calcification in the arteries and the deposition of 18F-sodium-fluoride (18F-NaF) in the skin and vessel walls with positron emission tomography/computed tomography. This was an observational study including 18 patients with PXE. Vascular calcification was measured in Agatston units, and deposition in the skin and vessel walls was shown using target-to-background ratio (TBR). Severity of the disease was scored by Phenodex. We found higher vascular calcification in the popliteal, femoral, and aortic arch vessels compared to other vascular regions; however, the uptake of radiotracer was the highest in the aorta and femoral arteries. In the skin, the highest uptake was observed in the neck and the axillae. There was no significant association between 18F-NaF deposition in the arteries or skin and the global Phenodex score. In contrast, the Phenodex score was significantly associated in univariate analyses with the averaged vascular calcium score (p < 0.01). In the neck, patients with higher skin Phenodex scores exhibited higher radiotracer uptake. As a conclusion, because vascular calcification is physiological, our data suggested that the detection of cutaneous (neck) 18F-NaF deposits might serve to monitor the calcification process in the short-term for patients with PXE.

Comparison of Correction Techniques for the Spill in Effect in Emission Tomography.

In positron emission tomography (PET) imaging, accurate clinical assessment is often affected by the partial volume effect (PVE) leading to overestimation (spill-in) or underestimation (spill-out) of activity in various small regions. The spill-in correction, in particular, can be very challenging when the target region is close to a hot background region. Therefore, this study evaluates and compares the performance of various recently developed spill-in correction techniques, namely: background correction (BC), local projection (LP), and hybrid kernelized (HKEM) methods. We used a simulated digital phantom and [18F]-NaF PET data of three patients with abdominal aortic aneurysms (AAA) acquired with Siemens Biograph mMR™ and mCT™ scanners respectively. Region of Interest (ROI) analysis was performed and the extracted SUV mean , SUV max and target-to-background ratio (TBR) scores were compared. Results showed substantial spill-in effects from hot regions to targeted regions, which are more prominent in small structures. The phantom experiment demonstrated the feasibility of spill-in correction with all methods. For the patient data, large differences in SUV mean , SUV max and TBR max scores were observed between the ROIs drawn over the entire aneurysm and ROIs excluding some regions close to the bone. Overall, BC yielded the best performance in spill-in correction in both phantom and patient studies.

Linear Enhancement Algorithm of Infrared Target Based on Adaptive Fractional Differentiation

To solve the problems associated with infrared images,such as narrow gray range,unclear image details and fuzzy target edge,an infrared target enhancement method based on adaptive fractional differentiation is proposed.In this method,first,the gradient and information entropy of image are used for effective fusion,and the fractional differentiation is adaptively adjusted to enhance the edge of the target in the image.Subsequently,the standard deviation and mean value of the image pixel gray are fused to determine the segmentation threshold of the target,to distinguish the background and target in the image.The target area of the image is linearly enhanced to better highlight the target.Experimental results show that the proposed method can effectively distinguish the target and background in the infrared image.The average local target-to-background ratio(TBR)increased by 0.5,and the visual effect was ideal.

18Fluoride-based molecular imaging of coronary atherosclerosis in HIV infected patients

Background and aimsMolecular imaging with 18Fluorodeoxyglucose (FDG) and 18F-sodium-fluoride (NaF) captures arterial inflammation and micro-calcification and can reveal potentially unstable atherosclerotic plaques. MethodsWe performed FDG and NaF PET/CT imaging in two clinically similar cohorts of patients living with HIV (PLWH) with no symptomatic cardiovascular disease. The prevalence and intensity of coronary artery uptake of each tracer, measured as target-to-background ratio (TBR), were assessed in patients at low and high cardiovascular risk. ResultsNinety-three PLWH were submitted to PET/CT imaging with FDG (N = 43) and NaF (N = 50); 42% were at low and 58% at high cardiovascular risk. The intensity of uptake and multivessel coronary artery uptake were significantly higher with NaF than FDG both in low and high-risk patients. When each 18F-tracer was tested in low and high-risk patients, an equal proportion of subjects showed no vessel, single and multivessel NaF uptake; the same was true for no and single vessel uptake of FDG (no multivessel FDG uptake was noted). Waist circumference, CRP, D-dimer, HIV duration and treatment with nucleoside reverse transcriptase inhibitors were associated with high NaF uptake in univariable analyses; D-dimer remained significant in multivariable analyses (OR = 1.05; p=0.02). There were no significant associations with FDG uptake. ConclusionsThe prevalence of coronary artery uptake was higher with NaF compared to FDG both in high and low risk patients, hence microcalcification imaging may be a more sensitive tool to detect coronary atherosclerosis than inflammation imaging. However, the uptake of each 18Fluoride tracer was similar between low and high-risk subjects, and this underscores the discordance between clinical and imaging based risk assessment. Future investigation should address the prognostic significance of NaF coronary artery uptake.

Systemic atherosclerotic plaque vulnerability in patients with Coronary Artery Disease with a single Whole Body FDG PET-CT scan.

Cardiovascular disease is a leading cause of morbimortality with over half cardiovascular events occurring in the asymptomatic population by traditional risk stratification. This preliminary study aimed to evaluate systemic plaque vulnerability in patients with prior Coronary Artery Disease (CAD) with a single Whole Body [FDG] PET-CT scan in terms of plaque inflammation and calcifications. Twenty-two patients referred for oncological evaluation and with prior history of advanced CAD or age and gender matched controls without cardiovascular disease, underwent a Whole Body PET-CT scan 90 min after injection of 18F-FDG. A total of 975 transaxial PET images were retrospectively analysed to assess plaque inflammation using a standardized method of analysis with averaged Target-to-Background Ratios (TBRs) at different levels, in the thoracic and abdominal aorta, carotids, LAD, common iliac and femoral arteries, and were correlated with calcium scores from the CT images. TBRs from the thoracic aorta were higher in male patients than controls (1.49±0.11, p<0.05) and a gradient was observed (ascending > descending > aortic arch), and were also higher in the carotids in female patients (1.43±0.07) versus controls (p<0.05). A tendency for higher levels of plaque inflammation in the abdominal aorta was noted in all groups, but no significant FDG uptake was found either in the iliac or femoral arteries in any group. Plaque inflammation was also higher in the LAD in males but with large variations. Higher levels of calcifications were noted in the LAD, infra-renal abdominal aorta and common iliac arteries, but without significant correlation with plaque inflammation except sporadic overlapping. Patients with advanced CAD are at risk for vulnerable inflamed atheromas in other territories such as the thoracic aorta and carotid arteries, underpinning the systemic nature of the atherosclerotic disease. Coexistence with calcifications is rare, suggesting a different functional status of the plaques and different stages of the disease. Evaluation of subclinical systemic plaque vulnerability in CAD with a Whole Body [FDG] PET-CT scan is feasible and a potentially useful biomarker to assess subclinical vascular risk for risk stratification and treatment optimization, but further studies are needed.

Visual Scoring Improves the Utility of 18F-FDG PET/CT in the Diagnosis of Aortic Graft Infection

Introduction - The diagnosis of aortic graft infection (AGI) is frequently complex. We aimed to assess the utility of 18F-FDG uptake (SUVmax ‘cutoff’ ≥3.8) or target-to-background ratio (TBR), plus visual scoring (Sah.B,EJVES;2015) in diagnosing AGI.

Short-term discontinuation of vagal nerve stimulation alters 18F-FDG blood pool activity: an exploratory interventional study in epilepsy patients

BackgroundVagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake.ResultsTen patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5–2.2) vs. 1.7 (1.2–2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1–1.4) vs. 1.0 (0.8–1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9–96.8) vs. 48.1 pmol/L (36.9–61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7–5.3) vs. 4.6 mmol/L (4.5–5.2); p = 0.075].ConclusionsShort-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.

Hybrid PET- and MR-driven attenuation correction for enhanced 18F-NaF and 18F-FDG quantification in cardiovascular PET/MR imaging

BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging. MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD). ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication. ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.

Imaging Inflammation in Atherosclerosis with CXCR4-Directed 68Ga-Pentixafor PET/CT: Correlation with 18F-FDG PET/CT.

C-X-C motif chemokine receptor 4 (CXCR4) is expressed on the surface of various cell types involved in atherosclerosis, with a particularly rich receptor expression on macrophages and T cells. First pilot studies with 68Ga-pentixafor, a novel CXCR4-directed PET tracer, have shown promise to noninvasively image inflammation within atherosclerotic plaques. The aim of this retrospective study was to investigate the performance of 68Ga-pentixafor PET/CT for imaging atherosclerosis in comparison to 18F-FDG PET/CT. Methods: Ninety-two patients (37 women and 55 men; mean age, 62 ± 10 y) underwent 68Ga-pentixafor and 18F-FDG PET/CT for staging of oncologic diseases. In these subjects, lesions in the walls of large arteries were identified using morphologic and PET criteria for atherosclerosis (n = 652). Tracer uptake was measured and adjusted for vascular lumen (background) signal by calculation of target-to-background ratios (TBRs) by 2 investigators masked to the other PET scan. On a lesion-to-lesion and patient basis, the TBRs of both PET tracers were compared and additionally correlated to the degree of arterial calcification as quantified in CT. Results: On a lesion-to-lesion basis, 68Ga-pentixafor and 18F-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). 68Ga-pentixafor PET identified more lesions (n = 290; TBR ≥ 1.6, P < 0.01) and demonstrated higher uptake than 18F-FDG PET (1.8 ± 0.5 vs. 1.4 ± 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both 68Ga-pentixafor and 18F-FDG uptake (r = -0.38 vs. -0.31, both P < 0.00001). Conclusion: CXCR4-directed imaging of the arterial wall with 68Ga-pentixafor PET/CT identified more lesions than 18F-FDG PET/CT, with only a weak correlation between tracers. Further studies to elucidate the underlying biologic mechanisms and sources of CXCR4 positivity, and to investigate the clinical utility of chemokine receptor-directed imaging of atherosclerosis, are highly warranted.

Clinical Factors Associated with Time-Specific Distribution of 18F-Fluorodeoxyglucose in Large-Vessel Vasculitis

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can detect vascular inflammation in large-vessel vasculitis (LVV). Clinical factors that influence distribution of FDG into the arterial wall and other tissues have not been characterized in LVV. Understanding these factors will inform analytic strategies to quantify vascular PET activity. Patients with LVV (n = 69) underwent 141 paired FDG-PET imaging studies at one and two hours per a delayed image acquisition protocol. Arterial uptake was quantified as standardized uptake values (SUVMax). SUVMean values were obtained for background tissues (blood pool, liver, spleen). Target-to-background ratios (TBRs) were calculated for each background tissue. Mixed model multivariable linear regression was used to identify time-dependent associations between FDG uptake and selected clinical features. Clinical factors associated with FDG distribution differed in a tissue- and time-dependent manner. Age, body mass index, and C-reactive protein were significantly associated with arterial FDG uptake at both time points. Clearance factors (e.g. glomerular filtration rate) were significantly associated with FDG uptake in background tissues at one hour but were weakly or not associated at two hours. TBRs using liver or blood pool at two hours were most strongly associated with vasculitis-related factors. These findings inform standardization of FDG-PET protocols and analytic approaches in LVV.

5965Perimatrial inflammation measured by fluoine-18-fluorodeoxyglucose-positron emission tomography/computed tomography to predict new-onset atrial fibrillation

Abstract Background Fluoine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a useful modality of inflammatory disease. Epicardial adipose tissue (EAT) contains abundant ganglionated plexi, therefore EAT inflammation may cause atrial arrhythmia, such as atrial premature contraction (APC) and atrial fibrillation (AF). Previous studies have shown that inflammatory activity of EAT has relation to the presence of AF. However, it is unknown whether EAT inflammation contributes to the occurrence of AF. Methods Out of 20720 examinees who underwent FDG-PET/CT for screening of cancer in the years 2012–2018, 151 (aged 65.6±12.0 years old, 62 females) had ambulatory electrocardiographic monitoring (Holter ECG) within a year and non-detection of AF. Standardized uptake value (SUV) was measured in fat adjacent to roof of left atrium (ROOF), atrioventricular groove (AV), left main coronary artery (LMT), and right ventricular blood pool (RV). In order to correct for blood pool activity, SUV of ROOF, AV, and LMT were divided by SUV of RV respectively, yielding target-to-background ratio (TBR). As regards to arterial inflammation, measurements were performed with SUV in ascending aorta (A-Ao) and in superior vena cava (SVC) as blood pool. In the same way, SUV of A-Ao was divided by SUV of SVC, yielding TBR. Results According to Holter ECG, APC≥100 beats per day was seen in 60 patients (Group A), but not in the other 91 (Group B). In Group A, TBR of ROOF, AV, and LMT were all significantly higher than Group B (p&lt;0.001, p=0.004, and p=0.008, respectively). During a median follow-up of 179 days, new-onset AF was diagnosed in 7 patients (4 in Group A (6.7%), 3 in Group B (3.3%), p=0.046). There was significant difference in TBR of ROOF between patients with and without new-onset AF (p&lt;0.001), but not in TBR of AV and LMT. In addition, no significant difference was observed in TBR of A-Ao between these two groups. In the Cox proportional hazard analysis, TBR of ROOF was found to be an independent predictor of new-onset AF (odds ratio 40.1, 95% confidence interval 6.05 to 265.9, p&lt;0.001). Conclusions Although EAT inflammation evaluated by SUV is related to frequent APCs, only in fat adjacent to roof of left atrium is associated with and predicts future occurrence of AF. Arterial inflammation measured by SUV has no relation to atrial arrhythmia.

P5302Significant correlation of visceral adiposity and adipocytokines with arterial inflammation in genetic dyslipidaemias

Abstract Background The adipose tissue is now established as a major regulator of cardiovascular status, mediated by the secretion of several bioactive molecules, including adipocytokines. Individuals with genetic dyslipidaemias of either familial combined hyperlipidemia (FCH) or heterozygous familial hypercholesterolemia (heFH) subtype are characterized by accelerated atherosclerosis. Nonetheless, limited data exists on the relationship between adiposity and arterial inflammation, a marker of cardiovascular risk, in this setting. Purpose To investigate the relationship between adiposity indices and arterial inflammation evaluated by 18F fluorodeoxyglycose positron emission tomography (PET/CT) in patients with hereditary lipid metabolism disorders. Methods Consecutive patients with either FCH or heFH, free of statin therapy, and normolipidaemic individuals underwent PET/CT imaging. Arterial FDG uptake was estimated as the average value of target-to-background ratio (TBR) within aortic and carotid wall. Volumes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured from CT images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by selecting all voxels with attenuation between −190 and −30 Hounsfield Units (HU). Serum adiponectin and leptin levels were measured with ELISA by available commercial kits. For comparisons with arterial TBR, adiponectin and leptin concentrations above and below the 25th percentile, were stratified as high and low, respectively. Results In total, 60 individuals (20 FCH, 20 heFH and 20 controls) were included. A modest but significant correlation between SAT volume and arterial TBR (R=0.386, p=0.004) was detected. This relationship did not remain significant after controlling for VAT volume (p=0.303). A strong correlation between VAT volume and arterial TBR (R=0.621, p=0.001) was observed. This relationship remained significant after controlling for SAT volume (R=0.541, p&lt;0.001). Arterial TBR values were higher in individuals with low plasma adiponectin levels (p=0.010). In addition, patients with higher leptin levels exhibited increased arterial FDG uptake compared to subjects with low serum leptin concentrations (p=0.05) Conclusions Abdominal adipose tissue imaging markers and serum adipocytokines correlate with arterial inflammation as assessed by PET/CT in patients with familial dyslipidaemias highlighting the role of abdominal adipose tissue for atherosclerosis progression in this population.