Background 18 F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18 F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18 F-NaF uptake with calcification visualized on microcomputed tomography (microCT). Methods Carotid plaques from stroke patients undergoing surgery were incubated in 18 F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18 F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18 F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. Results 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18 F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18 F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18 F-NaF PET VOI showed calcification on CT. Conclusions 18 F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18 F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development. Electronic supplementary material The online version of this article (10.1007/s12350-018-1325-5) contains supplementary material, which is available to authorized users.

Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors.

Background While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). Methods Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. Results Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. Conclusion This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.

Purpose: Severity of abdominal obesity and possibly levels of metabolic activity of abdominal visceral adipose tissue (VAT) are associated with an increased risk for cardiovascular disease (CVD). In this context, the purpose of the current study was to evaluate the reproducibility and repeatability of a semi-automated method for assessment of the metabolic activity of VAT using 2-deoxy-2-[ PET/low-dose (LD) CT scans within 1 week were included. Abdominal VAT was automatically segmented using CT between levels L1-L5. The initial CT-based segmentation was further optimized using PET data with a standardized uptake value (SUV) threshold approach (range 1.0-2.5) and morphological erosion (range 0-5 pixels). The [ 18 F]FDG uptake in SUV that was measured by the automated method was compared with manual analysis. The reproducibility and repeatability were quantified using intraclass correlation coefficients (ICCs).Results: The metabolic assessment of VAT on [ 18 F]FDG PET/LDCT scans expressed as SUV mean , using an automated method showed high inter and intra observer (all ICCs 9 0.99) and overall repeatability (ICC = 0.98). The manual method showed reproducible inter observer (all ICCs 9 0.92), but less intra observer (ICC = 0.57) and less overall repeatability (ICC = 0.78) compared with the automated method.

Purpose: 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) uptake is a marker of metabolic activity and is therefore used to measure the inflammatory state of several tissues. This radionuclide marker is transported through the cell membrane via glucose transport proteins (GLUTs). The aim of this study is to investigate whether insulin resistance (IR) or inflammation plays a role in [ 18 F]FDG uptake in adipose tissue (AT). Procedures: This study consisted of an in vivo clinical part and an ex vivo mechanistic part. In the clinical part, [ 18 F]FDG uptake in abdominal visceral AT (VAT) and subcutaneous AT (SAT) was determined using PET/CT imaging in 44 patients with early type 2 diabetes mellitus (T2DM) (age 63 [54-66] years, HbA1c [6.3 ± 0.4 %], HOMA-IR 5.1[3.1-8.5]). Plasma levels were Jan-Luuk Hillebrands and Douwe J. Mulder contributed equally to this work.

Angiogenic T (Tang) cells are mediators of vascular repair, and are characterized by surface expression of CXCR4. This receptor for stromal cell‐derived factor‐1α (SDF‐1α) is cleaved by dipeptidyl peptidase‐4 (DPP‐4). Tang cell levels were investigated in people with type 2 diabetes mellitus (T2DM) compared with matched healthy controls and after treatment with the DPP‐4 inhibitor Linagliptin. People with T2DM were randomized to 5 mg/day Linagliptin (n = 20) or placebo (n = 21) for 26 weeks. Tang cell frequency was identified in peripheral blood mononuclear cells (CD3+CD31+CXCR4+) and levels of endothelial progenitor cells (EPCs) (CD34+CD133+KDR+) were also assessed in whole blood. Circulating Tang cell levels were significantly lower in people with T2DM compared with the healthy control group. SDF‐1α levels increased significantly in Linagliptin‐treated people with T2DM compared to placebo, and a trend was observed in change of Tang cell levels, while EPC count did not change. In conclusion, circulating Tang cell levels were considerably lower in people with T2DM, while a trend was observed in recruitment of Tang cells after 26 weeks of treatment with Linagliptin. These data suggest that DPP‐4 inhibitors may potentially exert beneficial effects on bone marrow‐driven vascular repair.

Background Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16−, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. Methods Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. Results Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. Conclusions Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = −0.25 to −0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.