Target-to-background Ratio Research Articles

Pulmonary Artery 18F-Fluorodeoxyglucose Uptake by PET/CMR as a Marker of Pulmonary Hypertension in Sarcoidosis

ObjectivesThis study investigated whether pulmonary artery (PA) 18F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures. Background18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH). MethodsIn a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, 18F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE). ResultsThirty-three subjects demonstrated clear 18F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA 18F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA 18F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P < 0.05). In the subgroup that underwent TTE, signs of PH were present in a significantly higher number of patients with PA 18F-FDG uptake (14 [51.9%] vs 37 [29.8%]; P < 0.05). Qualitative assessment of 18F-FDG uptake in the PA wall showed a sensitivity of 33% and specificity of 96% for separating patients with PH based on RHC-derived PA pressures. SUVmax and TBR in the PA wall correlated with PA pressure derived from RHC and/or TTE. ConclusionsWe demonstrate that 18F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.

Comparing Semiquantitative and Qualitative Methods of Vascular 18F-FDG PET Activity Measurement in Large-Vessel Vasculitis.

The study rationale was to assess the performance of qualitative and semiquantitative scoring methods for 18F-FDG PET assessment in large-vessel vasculitis. Methods: Patients with giant cell arteritis or Takayasu arteritis underwent independent clinical and imaging assessments within a prospective observational cohort. 18F-FDG PET/CT scans were interpreted for active vasculitis by central reader assessment. Arterial 18F-FDG uptake was scored by qualitative visual assessment using the PET vascular activity score (PETVAS) and by semiquantitative assessment using SUVs and target-to-background ratios (TBRs) relative to liver or blood activity. The performance of each scoring method was assessed by intrarater reliability using the intraclass correlation coefficient (ICC) and areas under the receiver-operating-characteristic curve, applying physician assessment of clinical disease activity and reader interpretation of vascular PET activity as independent reference standards. The Wilcoxon signed-rank test was used to analyze change in arterial 18F-FDG uptake over time. Results: Ninety-five patients (giant cell arteritis, 52; Takayasu arteritis, 43) contributed 212 18F-FDG PET studies. The ICC for semiquantitative evaluation (0.99 [range, 0.98-1.00]) was greater than the ICC for qualitative evaluation (0.82 [range, 0.56-0.93]). PETVAS and target-to-background ratio metrics were more strongly associated with reader interpretation of PET activity than SUV metrics. All assessment methods were significantly associated with physician assessment of clinical disease activity, but the semiquantitative metric liver tissue-to-background ratio (TBRLiver) achieved the highest area under the receiver-operating-characteristic curve (0.66). Significant but weak correlations with C-reactive protein were observed for SUV metrics (r = 0.19, P < 0.01) and TBRLiver (r = 0.20, P < 0.01) but not for PETVAS. In response to increased treatment in 56 patients, arterial 18F-FDG uptake was significantly reduced when measured by semiquantitative (TBRLiver, 1.31-1.23; 6.1% change; P < 0.0001) or qualitative (PETVAS, 22-18; P < 0.0001) methods. Semiquantitative metrics provided information complementary to qualitative evaluation in cases of severe vascular inflammation. Conclusion: Both qualitative and semiquantitative methods of measuring arterial 18F-FDG uptake are useful in assessing and monitoring vascular inflammation in large-vessel vasculitis. Compared with qualitative metrics, semiquantitative methods have superior reliability and better discriminate treatment response in cases of severe inflammation.

Feasibility of semiquantitative 18F-fluorodeoxyglucose PET/computed tomography in patients with advanced lung cancer for interim treatment evaluation of combining immunotherapy and chemotherapy.

This study aimed to investigate the prognosis value of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in advanced lung cancer patients with immunotherapy combined with chemotherapy. Fifty-one advanced lung cancer patients were included in this retrospective study, who underwent 18F-FDG PET/CT imaging before four cycles of immunotherapy combined with chemotherapy at our institution between January 2018 and January 2020. The following PET/CT parameters were calculated: standardized uptake value SUVmax, SUVmean, SUVpeak, SUVsd, metabolic tumor volume (MTV), total lesion glycolysis (TLG), MTV25%, MTV42%, MTV50%, MTV75%, global lung glycolysis (GLG), target-to-background ratio (TBR), SUVpeakwb, MTVwb, TLGwb, SUVmeanwb, SUVmaxwb. Logistics regression analyses were used for assessing the association between baseline metabolic parameters and response to treatment. Kaplan-Meier estimator curves and the log-rank test were constructed for survival analyses. According to RECIST, nine patients (18%) showed partial response, 25 (49%) had SD, and 17 (33%) had progressive disease. The mean ± SD of SUVmax, SUVpeak, MTV were lower in clinical benefit (CB) group than no-clinical benefit (no-CB) group (all P < 0.05). Median PFS was 3.7 months in no-CB group and 9.9 months in CB group (P < 0.001). Multivariate logistic analysis indicated that SUVmax and histology were independent factors significantly related to the evaluation of therapeutic efficiency. Furthermore, SUVmax is an independent predictor of efficacy in non-small cell lung cancer. SUVmax can be used to predict interim treatment response of immunotherapy combination with chemotherapy for advanced lung cancer. Moreover, the combination of SUVmax and histology may predict treatment response with acceptable reliability. However, a large prospective multicenter trial is still needed to examine the above finding for lacking limited evidence.

Total-body 18F-FDG PET/CT scan in oncology patients: how fast could it be?

The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR

Background and aimsElectronic cigarette (EC) use is popular among youth, touted as a safer alternative to smoking and promoted as a tool to aid in smoking cessation. EC cardiovascular safety however is not well established. The aim of this study was to examine cardiovascular consequences of EC use by evaluating their effect on the entire atherosclerotic cascade in young adults using noninvasive combined positron emission tomography (PET)/magnetic resonance imaging (MR) and comparing EC use with age matched smokers of traditional cigarettes and nonsmoking controls. MethodsCarotid PET/MR was applied to look at vascular inflammation (18-fluorodeoxyglucose (FDG)-PET) and plaque burden (multi-contrast MR of vessel wall) from 60 18-30 year-old subjects (20 electronic cigarette users, 20 traditional smokers and 20 nonsmokers). ResultsGroups were reasonably well balanced in terms of age, gender, demographics, cardiovascular risk and most biomarkers. There were no differences in vascular inflammation as measured by 18-FDG-PET target to background ratios (TBR) between EC users, traditional cigarette smokers and nonsmokers. However, measures of carotid plaque burden − wall area, normalized wall index, and wall thickness − measured from MR were significantly higher in both traditional smokers and EC users than in nonsmokers. ConclusionsYoung adult EC users, smokers and nonsmokers in our study did not exhibit vascular inflammation as defined by 18-F-FDG-PET TBR max, but smokers and EC users had significantly more carotid plaque burden compared to matched nonsmokers. Results could indicate that vaping does not cause an increase in vascular inflammation as measured by FDG-PET.

Clinical and FDG-PET/CT correlates in patients with polymyalgia rheumatica.

We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings. Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods. Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV. Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [18F]FDG PET/CT

ObjectivesTo compare block sequential regularized expectation maximization (BSREM) and ordered subset expectation maximization (OSEM) for the detection of in-transit metastasis (ITM) of malignant melanoma in digital [18F]FDG PET/CT.MethodsWe retrospectively analyzed a cohort of 100 [18F]FDG PET/CT scans of melanoma patients with ITM, performed between May 2017 and January 2020. PET images were reconstructed with both OSEM and BSREM algorithms. SUVmax, target-to-background ratio (TBR), and metabolic tumor volume (MTV) were recorded for each ITM. Differences in PET parameters were analyzed with the Wilcoxon signed-rank test. Differences in image quality for different reconstructions were tested using the Man-Whitney U test.ResultsBSREM reconstruction led to the detection of 287 ITM (39% more than OSEM). PET parameters of ITM were significantly different between BSREM and OSEM reconstructions (p < 0.001). SUVmax and TBR were higher (76.5% and 77.7%, respectively) and MTV lower (49.5%) on BSREM. ITM missed with OSEM had significantly lower SUVmax (mean 2.03 vs. 3.84) and TBR (mean 1.18 vs. 2.22) and higher MTV (mean 2.92 vs. 1.01) on OSEM compared to BSREM (all p < 0.001).ConclusionsBSREM detects significantly more ITM than OSEM, owing to higher SUVmax, higher TBR, and less blurring. BSREM is particularly helpful in small and less avid lesions, which are more often missed with OSEM.Key Points• In melanoma patients, [18F]FDG PET/CT helps to detect in-transit metastases (ITM), and their detection is improved by using BSREM instead of OSEM reconstruction.• BSREM is particularly useful in small lesions.

Association of Inflammatory Metabolic Activity of Psoas Muscle and Acute Myocardial Infarction: A Preliminary Observational Study with 18F-FDG PET/CT.

Inflamed skeletal muscle promotes chronic inflammation in atherosclerotic plaques, thereby contributing to the increased risk of coronary artery disease (CAD). In this study, we evaluated the metabolic activity of psoas muscle, using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), and its association with carotid artery inflammation and acute myocardial infarction (AMI). In total, 90 participants (32 AMI, 33 chronic stable angina (CSA), and 25 control) were enrolled in this prospective study. Metabolic activity of skeletal muscle (SM) was measured by using maximum standardized uptake value (SUVmax) of psoas muscle, and corresponding psoas muscle area (SM area) was also measured. Carotid artery inflammation was evaluated by using the target-to background ratio (TBR) of carotid artery. SM SUVmax was highest in AMI, intermediate in CSA, and lowest in control group. SM SUVmax was significantly correlated with carotid artery TBR and systemic inflammatory surrogate markers. Furthermore, SM SUVmax was independently associated with carotid artery TBR and showed better predictability than SM area for the prediction of AMI. Metabolic activity of psoas muscle assessed by 18F-FDG PET/CT was associated with coronary plaque vulnerability and synchronized with the carotid artery inflammation in the participants with CAD. Furthermore, it may also be useful to predict AMI.

ImmunoPET imaging of human CD8+ T cells with novel 68Ga-labeled nanobody companion diagnostic agents

BackgroundAlthough immunotherapy has revolutionized treatment strategies for some types of cancers, most patients failed to respond or obtain long-term benefit. Tumor-infiltrating CD8+ T lymphocytes are closely related to the treatment outcome and prognosis of patients. Therefore, noninvasive elucidation of both systemic and tumor-infiltrating CD8+ T lymphocytes is of extraordinary significance for patients during cancer immunotherapy. Herein, a panel of 68Ga-labeled Nanobodies were designed and investigated to track human CD8+ T cells in vivo through immuno-positron emission tomography (immunoPET).ResultsAmong the screened Nanobodies, SNA006a showed the highest binding affinity and specificity to both human CD8 protein and CD8+ cells in vitro, with the equilibrium dissociation constant (KD) of 6.4 × 10−10 M and 4.6 × 10−10 M, respectively. 68Ga-NOTA-SNA006 was obtained with high radiochemical yield and purity, and stayed stable for at least 1 h both in vitro and in vivo. Biodistribution and Micro-PET/CT imaging studies revealed that all tracers specifically concentrated in the CD8+ tumors with low accumulation in CD8− tumors and normal organs except the kidneys, where the tracer was excreted and reabsorbed. Notably, the high uptake of 68Ga-NOTA-SNA006a in CD8+ tumors was rapid and persistent, which reached 24.41 ± 1.00% ID/g at 1.5 h after intravenous injection, resulting in excellent target-to-background ratios (TBRs). More specifically, the tumor-to-muscle, tumor-to-liver, and CD8+ to CD8− tumor was 28.10 ± 3.68, 5.26 ± 0.86, and 19.58 ± 2.70 at 1.5 h, respectively. Furthermore, in the humanized PBMC-NSG and HSC-NPG mouse models, 68Ga-NOTA-SNA006a accumulated in both CD8+ tumors and specific tissues such as liver, spleen and lung where human CD8 antigen was overexpressed or CD8+ T cells located during immunoPET imaging.Conclusions68Ga-NOTA-SNA006a, a novel Nanobody tracer targeting human CD8 antigen, was developed with high radiochemical purity and high affinity. Compared with other candidates, the long retention time, low background, excellent TBRs of 68Ga-NOTA-SNA006a make it precisely track the human CD8+ T cells in mice models, showing great potential for immunotherapy monitoring and efficacy evaluation.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Effect of moderate-intensity statin therapy on plaque inflammation in patients with acute coronary syndrome: A prospective interventional study evaluated by 18F-FDG PET/CT of the carotid artery.

Asian patients with acute coronary syndrome (ACS) are frequently prescribed moderate- -intensity statin in real practice, even during the early stage of ACS. Under assessment herein was the effect of moderate-intensity statin therapy on the resolution of plaque inflammation during the first month after ACS, a period with highest recurrent ischemic events, using dual time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). This prospective study included statin-naïve patients with ACS and non-calcified carotid plaques (≥ 3 mm on ultrasound images). Baseline FDG PET/CT images of the carotid arteries of the patients were obtained. Then, all patients received atorvastatin (20 mg/day); follow-up FDG PET/CT images of the carotid arteries were then obtained after 1 month of therapy. The primary endpoint measurement was the change in the target-to-background ratio (TBR) of the carotid artery between the initial and follow-up FDG PET/CT scans. Thirteen ACS patients completed the initial and follow-up FDG PET/CT scans. Moderate-intensity statin therapy failed to reduce plaque inflammation at 1 month after ACS (TBR 1.60 ± 0.20 at baseline vs. 1.50 ± 0.40 after therapy; p = 0.422) but significantly reduced serum low-density lipoprotein cholesterol (LDL-C) levels (mean LDL-C 101.2 ± 21.1 mg/dL at baseline vs. 70.7 ± 12.4 mg/dL after therapy; p < 0.001). Changes in the TBR and serum LDL-C levels were not correlated (r = -0.27, p = 0.243). Dual time point FDG PET/CT imaging demonstrates that moderate-intensity statin therapy was insufficient in suppressed plaque inflammation within the first month after ACS in Asian patients, even though achieving target LDL levels.

Lymphoma Severity and Type Are Associated With Aortic FDG Uptake by 18F-FDG PET/CT Imaging

BackgroundThere is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. ObjectivesThe aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. MethodsSixty-two chemotherapy-naïve patients with active Hodgkin’s or non-Hodgkin’s lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography–computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. ResultsMTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin’s lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin’s lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (β = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (β = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). ConclusionsAortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Evidence for uncoupling of clinical and 18-FDG activity of PET/CT scan improvement in tocilizumab-treated patients with large-vessel giant cell arteritis.

Clinical improvement following tocilizumab (TCZ) therapy in patients with large-vessel (LVV) giant cell arteritis (GCA) is well established. However, information on TCZ effect on imaging vascular activity is limited. We aimed to determine if clinical improvement correlated with reduction of vascular 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET/CT) scans. Observational study of patients with refractory LVV-GCA treated with TCZ who had a baseline and a follow-up 18F-FDG-PET/CT scan. For the visual analysis of 18F-FDG vascular uptake, a total vascular score (TVS) was defined, ranging from 0 to 15. Besides, a semiquantitative analysis was performed as a target to background ratio (TBR)= SUVmax thoracic aorta wall/SUVmax aortic vascular pool. The baseline and follow-up TVS and TBR were compared. Clinical and lab¬oratory outcomes were also assessed. We included 30 patients (24 women/6 men); mean age± standard deviation 65.7± 9.8 years. Baseline PET/CT scans were performed due to active disease at a median [interquartile range-IQR] of 1.5 [0.0-4.0] months before TCZ onset. Following TCZ therapy, 25 (83.33%) patients achieved clinical remission and reduction of 18F-FDG vascular uptake was also observed after a mean ± standard deviation of 10.8±3.7 months. TBR decreased from 1.70 ± 0.52 to 1.48 ± 0.25 (p=0.005) and TVS from 4.97±2.62 to 3.13±1.89 (p< 0.001). However, only 9 (30.0%) patients showed complete normalisation of TBR and only 3 (10%) normalisation of TVS. TBR and TVS showed a good correlation (r=0.576). Although most of LVV-GCA patients achieve clinical remission after TCZ therapy, less than one-third show normalisation of 18F-FDG vascular uptake.

The effects of chemotherapy on arterial inflammation assessed by 18 FDG PET-CT in patients with Lymphoma

Abstract Introduction Anti-cancer treatment can lead to increased cardiovascular morbidity among lymphoma survivors. This may be the result of direct effect of treatment on heart function, or indirect acceleration of atherosclerosis. 18F-fluorodeoxyglucose (FDG) uptake is a sensitive and robust marker for assessment of atherosclerotic inflammation. Purpose To investigate the effects of chemotherapy on arterial inflammation using FDG-PET CT in patients with lymphoma. Methods Fifty nine (mean age 58±17 years) patients with Hodgkin (n=39) or non-Hodgkin lymphomas (n=20) underwent 18FDG PET-CT imaging at baseline, interim and after completion of chemotherapy as part of their routine protocol. Arterial inflammation was assessed by arterial target to background ratio (TBR) of the aortic wall along the entire aorta. The index vessel TBR (the vessel with the higher value at baseline) was used for assessment of arterial inflammation. Patients with Hodgkin Lymphomas (HL) underwent therapy with Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim of their treatment was set at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non Hodgkin Lymphomas (NHL) underwent therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone+rituximab (R-CHOP). The interim of their treatment was set at 2 weeks post the 4th chemotherapy cycle. All patients we reassessed 6 weeks after chemotherapy completion. Results There were no differences in age and atherosclerotic risk factors (hypertension, diabetes, dyslipidemia and smoking), between the two groups (all P&amp;gt;0.05). Similarly, there were no differences in mean (±SD) index vessel TBR between HL and NHL patients (2.4±0.7 vs 2.7±0.9, respectively, P=0.65). In the whole study population the index vessel TBR progressively decreased after the end of therapy (by 0.53±0.11, from baseline to 6 weeks following the end of therapies) (F=10.94, P&amp;lt;0.001, ANOVA). The index vessel TBR decreased in both HL and NHL patients at 6 weeks after therapy compared to baseline level (all P&amp;lt;0.01, ANOVA, figure). The decrease at the interim scan was more pronounced in NHL compared to HL patients, however at 6 weeks after chemotherapy completion the index vessel TBR decreased further in patients with HL, while it increased slightly compared to interim levels in NHL patients (figure 1). Conclusion Arterial inflammation is reduced during and post-chemotherapy in patients with lymphoma. The index vessel TBR changes at the interim phase and 6 weeks after therapy completion indicate a different effect of specific treatment regimes in arterial inflammation between HL and NHL patients. Figure 1 Funding Acknowledgement Type of funding source: None

Coronary plaque instability is associated with inflammatory activity of visceral adipose tissue and carotid artery: a prospective pilot F-18 FDG PET/CT study

Abstract Background Dysfunctional Visceral adipose tissue (VAT) secretes pro-inflammatory cytokines and promotes inflammatory cell infiltration into VAT thereby boosting insulin resistance and systemic inflammation which eventually lead to increased risk of cardiovascular disease (CVD). F-18 FDG PET/CT is well known to reflect the inflammatory activity of classically activated (M1) macrophage. Purpose We hypothesized that F-18 FDG PET/CT could reflect the inflammatory activity of dysfunctional VAT and carotid artery which were associated with coronary plaque instability. Methods A total of 90 participants were enrolled in this prospective study. F-18 FDG PET/CT was performed in 32 participants with acute myocardial infarction (AMI) within a week of disease onset, 33 participants with stable coronary artery disease (CAD), and 25 control subjects. Maximum standardized uptake value (SUVmax) was calculated in VAT, subcutaneous adipose tissue (SAT), spleen, and bone marrow (BM). Target-to-background ratio (TBR) was calculated in right carotid artery and right jugular vein. Results The SUVmax of VAT and the TBR of right carotid artery were highest in patients with AMI, intermediate in patient with stable CAD, and lowest in control subjects. Systemic inflammation surrogate markers such as high-sensitivity C-reactive protein, spleen SUVmax were also showed similar pattern like the SUVmax of VAT and the TBR of right carotid artery. Furthermore, multiple linear regression analysis showed that the SUVmax of VAT and spleen SUVmax were independently associated with the TBR of right carotid artery. Conclusions F-18 FDG PET/CT could reflect the synchronized systemic inflammation in VAT and carotid artery which could affect the coronary artery instability. Furthermore, our findings offer clinical insights into risk stratification, monitoring of therapy, and physiological changes in the development of CAD. Funding Acknowledgement Type of funding source: None

Severity and type of lymphoma are associated with aortic 18-fluorodeoxyglucose (FDG) positron emission tomographic uptake assessed by FDG PET/CT imaging

Abstract Introduction There is increasing evidence that metabolic disease burden in lymphoma influence patients' outcome.However, the impact of disease severity on cardiovascular system remains unknown. Purpose To assess whether lymphoma is associated with arterial inflammation by examining the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. Methods Sixty-two patients (43 male, mean age 58±18 years) with Hodgkin (n=29) or non-Hodgkin lymphoma (n=33) before chemotherapy and two separate control groups of 14 and 16 healthy individuals for Hodgkin and non-Hodgkin population respectively, with similar age, sex and cardiovascular risk factors,underwent FDG position emission tomography (FDG-PET/CT) imaging.Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis (TLG) corresponding to standard uptake values (SUV) ≥41% or ≥2.5 of maximum SUV within lymphoma regions, and aortic FDG uptake by target-to-background ratio (TBR). Serum high sensitivity-C-reactive protein (hs-CRP), white blood count (WBC), ratio of neutrophils to lymphocytes (N/L), albumin and lactic acid dehydrogenase (LDH) values were measured for patient group. Results MTV and TLG measurements correlated significantly with hs-CRP, WBC,N/L ratio,albumin and LDH table 1.Patients with non-Hodgkin or Hodgkin lymphoma had increased aortic TBR compared to controls (p=0.001 and p=0.023, respectively).Aortic TBR was higher in patients with stage III-IV disease compared to those with stage I-I (p=0.046).There were significant associations between aortic FDG uptake and MTV values, which remained significant after adjustment for confounders (β=0.353, p=0.001, adjusted R2=0.318 for MTV41%, β=0.442, p=0.001, adjusted R2=0.269 for MTV2.5), Figure 1. Conclusions Aortic wall FDG uptake is related with disease severity indicating a vascular effect of lymphoma, as well as a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences to vascular beds with a single examination. Figure 1 Funding Acknowledgement Type of funding source: None

Serum uric acid in asymptomatic adults is weakly associated with carotid artery FDG uptake but not intima-media thickness

BackgroundThis study investigated the association of serum uric acid (UA) with carotid fluoro-2-deoxyglucose (FDG) uptake as a marker of inflammatory atherosclerosis. Methods and resultsIn this cross-sectional retrospective study of 970 otherwise healthy adults, subjects in the greater serum UA quartiles had higher triglyceride (P < .001), lower high-density lipoprotein cholesterol (P < .05), and lower estimated GFR (P < .001). Mean and maximum Target-to-background ratios (TBRs) of carotid FDG uptake measured by positron emission tomography were significantly increased across greater serum UA quartiles (1.35 and 1.57 for Q1, 1.38 and 1.60 for Q2, 1.39 and 1.62 for Q3, and 1.39 and 1.61 for Q4; P = .001 and < .001). Carotid intima-media thickness was not different. Serum UA showed weak but significant correlations with estimated GFR (P < .001), and with mean (P < .001) and maximum carotid TBR (P = .004). Serum UA correlated with mean TBR in male (P = .008) and female subjects (P = .011), in high (≥ 70; P = .015) and low estimated GFR (< 70; P = .035), and in normotensive (P = .001) but not in hypertensive subjects. ConclusionsElevated serum UA in asymptomatic adults is associated with increased carotid FDG uptake, which suggests a potential role of UA in carotid inflammatory atherosclerosis.

Factors relevant to atrial 18F-fluorodeoxyglucose uptake in atrial fibrillation

BackgroundThis retrospective study was designed to explore the factors relevant to increased atrial 18F-fluorodeoxyglucose (FDG) uptake in patients with atrial fibrillation (AF) who had undergone routine whole-body positron emission tomography/computed tomography (PET/CT) imaging. Methods and ResultsForty-eight consecutive AF patients (32 persistent, 16 paroxysmal) were identified from our routine FDG PET/CT database. Twenty-two control subjects were selected to establish the normal range of FDG uptake (maximum standardized uptake value, SUVmax) in target tissues. A target-to-background ratio (TBR) was calculated to determine abnormal uptake in the atrium and atrial appendage (AA). Univariate comparisons and multivariate regression analyses were conducted to explore the factors associated with the increased FDG accumulation in the atrium and AA. Seventeen AF patients, all with persistent AF, had increased atrial FDG uptake. Most of them (14, or 82.4%) had increased uptake in the right atrium. Eleven AF patients, 9 with persistent AF, had increased uptake in the AA, and bilateral AAs were equally involved. Multivariate logistic regression analyses identified that female gender, persistent AF, and activity in epicardial adipose tissue (EAT) were independent factors predicting the increased activity of the atrium; also, SUVmax of the left ventricle was found for the AA. In addition, multivariate linear regression analyses showed that EAT activity was the only independent variable linearly correlated with the activity of the atrium and AA. ConclusionsAtrial uptake was present in persistent AF and localized mainly in the right atrium, whereas bilateral AAs could be equally involved. Multiple factors contributed to the increased activity in atrium; in particular, the EAT activity was independently correlated with the activity of the atrium and AA.

Association of glucose uptake of visceral fat and acute myocardial infarction: a pilot 18F-FDG PET/CT study

BackgroundInflamed visceral adipose tissue (VAT) facilitates chronic inflammation in atherosclerotic lesions thereby leading to increased risk of coronary artery disease (CAD). In this study, we evaluated the glucose uptake of VAT and the carotid artery with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and their association with CAD, including acute myocardial infarction (AMI).MethodsA total of 90 participants were enrolled (32 with AMI, 33 with chronic stable angina; CSA, and 25 control participants) and undertook 18F-FDG PET/CT. VAT glucose uptake was measured by using maximum standardized uptake value (SUVmax) of VAT region. The target-to-background ratio (TBR) of carotid artery was defined as the SUVmax of carotid artery divided by the SUVmax of jugular vein. The SUVmax of spleen, bone-marrow (BM), and high-sensitivity C-reactive protein (hsCRP) were used for the assessment of systemic inflammatory activity.ResultsVAT SUVmax was highest in participants with AMI, intermediate in participants with CSA, and lowest in control participants. Carotid artery TBR and systemic inflammatory surrogate markers including spleen SUVmax, BM SUVmax, and hsCRP were also higher in the AMI group than in the CSA or control group. Furthermore, VAT SUVmax showed significant positive correlation with carotid artery TBR, spleen SUVmax, BM SUVmax, and hsCRP. In multivariate linear regression and logistic regression analyses, VAT SUVmax was independently associated with carotid artery TBR and AMI.ConclusionsGlucose uptake of VAT assessed by 18F-FDG PET/CT was associated with the severity of CAD and synchronized with the carotid artery inflammation in participants with CAD.

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.