Tissue-to-background Ratio Research Articles

Rosuvastatin effect on atherosclerotic plaque microcalcification

Abstract Background and Aims Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. Methods Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. Results Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years-old, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7±18.7% for ASCVD systems. After six months of rosuvastatin treatment (n=34), low-density lipoprotein cholesterol lowered from 133.6±33.8 to 58.8±20.7 mg.dL-1 (60% relative reduction, p<0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p<0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p=0.003). Conclusion In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.Graphical abstractTrial design

Distinguishing Axillary Lymphadenopathy after COVID-19 Vaccination from Malignant Lymphadenopathy.

Objectives: To study the differences between malignant hypermetabolic axillary lymphadenopathy (MHL) and COVID-19 vaccine-associated axillary hypermetabolic lymphadenopathy (VAHL) using clinical imaging. Methods: A total of 1096 patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) between 1 June 2021 and 30 April 2022 at Ehime University Hospital. In total, 188 patients with axillary lymphadenopathy after the COVID-19 vaccination were evaluated. The patients were classified into three groups such as VAHL (n = 27), MHL (n = 21), and equivocal hypermetabolic axillary lymphadenopathy (EqHL; n = 140). Differences in lymph node (LN) swellings were statistically analyzed using clinical imaging (echography, CT, and 18F-FDG PET). Results: MHL included a higher female population (90.5%) owing to a higher frequency of breast cancer (80.9%). Axillary LNs of MHL did not show any LN fatty hilums (0%); however, those of VAHL and EqHL did (15.8 and 36%, respectively). After the logistic regression analysis of the patients who had axillary lymphadenopathy without any LN fatty hilums, the minor axis length and ellipticity (minor axis/major axis) in the largest axillary LN, SUVmax, and Tissue-to-Background Ratio (TBR) were useful in distinguishing malignant lymphadenopathies. A receiver-operating characteristic (ROC) analysis indicated that a cut-off value of ≥7.3 mm for the axillary LN minor axis (sensitivity: 0.714, specificity: 0.684) and of ≥0.671 for ellipticity (0.667 and 0.773, respectively) in the largest LN with the highest SUVmax and TBR were predictive of MHL. Conclusions: Axillary lymphadenopathy of the minor axis and ellipticity in LN without fatty hilums may be useful to be suspicious for malignancy, even in patients who have received COVID-19 vaccination. Further examinations, such as 18F-FDG PET, are recommended for such patients.

Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting

Background18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of...

In Vivo Classification and Characterization of Carotid Atherosclerotic Lesions with Integrated 18F-FDG PET/MRI.

The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

Diagnostic Accuracy of FDG PET for the Identification of Vascular Graft Infection

Fluorodeoxyglucose (FDG) positron emission tomography (FDG PET/CT) can be used to identify and localize infection in patients with vascular graft infections (VGI). We aimed to evaluate the diagnostic accuracy of 18F-FDG PET/CT by defining thresholds for standardized uptake value (SUV) and tissue-to-background ratio (TBR) that would accurately identify the presence of vascular graft infection. Patients with suspected VGI were prospectively recruited and underwent 18F-FDG PET/CT scans. Diagnosis was based on clinical, laboratory and radiologic findings, and blinded to the results of the PET/CT scan. Receiver operator characteristics (ROC) curve analysis was done to determine optimal thresholds for SUV and TBR. Our final cohort consisted of 28 patients with suspected VGI (mean±SD age 67±10years, 61% men), of which 15 patients (54%) had definitive VGI. The cohort included 61% prosthetics grafts and 39% stent-grafts. The type of graft included in this study were biologic (4%), Dacron (64%) and Polytetrafluoroethylene (32%). The location of the implanted grafts was aortic (54%) and peripheral arterial reconstruction (46%). The location of the peripheral graft was 77% in lower extremity and 23% in the upper extremity (arterio-venous grafts for dialysis access). Using ROC analysis, SUV max of 4.5, SUV mean of 3.7, and a TBR of 1.6 gave the best balance between sensitivity and specificity (93%/92%, 100%/92% and 93%/92%, respectively). All thresholds had an area under the curve ≥0.93 and correct reclassification rate ≥93%. Our data suggests that FDG PET/CT can be used to reliably and accurately diagnose VGI. The dual anatomic-physiologic information from FDG PET/CT can complement clinical diagnosis particularly in uncertain cases.

Pancreatic imaging using diffusivity mapping – Influence of sequence technique on qualitative and quantitative analysis

PurposeTo compare image quality of an optimized diffusion weighted imaging (DWI) sequence with advanced post-processing and motion correction (advanced-EPI) to a standard DWI protocol (standard-EPI) in pancreatic imaging. Materials and methods62 consecutive patients underwent abdominal MRI at 1.5 T were included in this retrospective analysis of data collected as part of an IRB approved study. All patients received a standard-EPI and an advanced-EPI DWI with advanced post-processing and motion correction. Two blinded radiologists evaluated the parameters image quality, detail of parenchyma, sharpness of boundaries and discernibility from adjacent structures on b = 900 s/mm2 images using a Likert-like scale. Segmentation of pancreatic head, body and tail were obtained and apparent diffusion coefficient (ADC) was calculated separately for each region. Apparent tissue-to-background ratio (TBR) was calculated at b = 50 s/mm2 and at b = 900 s/mm2. ResultsThe advanced-EPI yielded significantly higher scores for pancreatic parameters of image quality, detail level of parenchyma, sharpness of boundaries and discernibility from adjacent structures in comparison to standard-EPI (p < 0.001 for all, kappa = [0.46,0.71]) and was preferred in 96% of the cases when directly compared. ADC of the pancreas was 7% lower in advanced-EPI (1.236 ± 0.152 vs. 1.146 ± 0.126 μm2/ms, p < 0.001). ADC in the pancreatic tail was significantly lower for both sequences compared to head and body (all p < 0.001). There was comparable TBR for both sequences at b = 50 s/mm2 (standard-EPI: 19.0 ± 5.9 vs. advanced-EPI: 19.0 ± 6.4, p = 0.96), whereas at b = 900 s/mm2, TBR was 51% higher for advanced-EPI (standard-EPI: 7.1 ± 2.5 vs. advanced-EPI: 10.8 ± 5.1, p < 0.001). ConclusionAn advanced DWI sequence might increase image quality for focused imaging of the pancreas and providing improved parenchymal detail levels compared to a standard DWI.

Vascular Inflammation and Cardiovascular Burden in Metastatic Breast Cancer Female Patients Receiving Hormonal Treatment and CDK 4/6 Inhibitors or Everolimus

Background: Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk.Purpose: To investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment.Methods: 22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment.Results: At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (p = 0.004), daytime SBP (p = 0.004) and night time SBP (p = 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect- p = 0.035, Interaction effect-p = 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p = 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-p = 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM.Conclusion: CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.

Vascular inflammation and cardiovascular burden in metastatic breast cancer female patients receiving hormonal treatment and CDK 4/6 inhibitors or everolimus

Abstract Background Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk. Purpose The aim of this study was to investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving either CDK 4/6 inhibitors and hormonal treatment or standard everolimus and hormonal treatment. Methods 22 consecutive female patients with metastatic breast cancer that expressed estrogen and /or progesteron receptor and were HER2-negative were enrolled. Patients with active infection, chronic autoimmune disease and history of chemotherapy for the metastatic disease and/or adjuvant chemotherapy during the past 3 years were excluded. All subjects received hormonal treatment and of those, 10 received everolimus and 12 received therapy with CDK 4/6 inhibitors. The two groups were matched for age, history of hypertension, diabetes, dyslipidemia, smoking and all were free of major cardiovascular events for the past 6 months. Regional wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiographic study were obtained followed by 24 hour ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall (ascending, arch, descending, abdominal), was quantified as tissue-to-background ratio (TBR).Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment. Results At follow up, patients assigned to CDK4/6 treatment demonstrated increased measurements of 24 hour systolic blood pressure (SBP) (p=0.004), daytime SBP(p=0.004) and night time SBP (p=0.012) (Group effect). The 24 hour mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values. (Group effect- p=0.035, Interaction effect-p=0.023).Additionally, 24 hour diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p=0.010). In CDK 4/6 group, TBR aorta measurements also increased significantly, whereas TBR values in everolimus remained stable. (Interaction effect-p=0.049). Both therapeutic regimens displayed statistically significant damaging effect with regards to the following variables: Night-time SBP (p=0.032), RWT (p&amp;lt;0.001), and LVM (p&amp;lt;0.001). Conclusion Chemotherapy with novel CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure values compared to the combination of everolimus and hormonal treatment in female patients with HR-positive HER2-negative metastatic breast cancer. Moreover, both treatment strategies promote remodelling of the left ventricle by means of increased RWT and mass. Further research and longitudinal studies in this field are required to validate the above findings. Funding Acknowledgement Type of funding source: None

Physiological Appearance of Hybrid FDG–Positron Emission Tomography/Computed Tomography Imaging Following Uncomplicated Endovascular Aneurysm Sealing Using the Nellix Endoprosthesis

Purpose: To investigate the physiological uptake of hybrid fluorine-18-fluorodeoxyglucose (FDG)–positron emission tomography/computed tomography (PET/CT) before and after an uncomplicated endovascular aneurysm sealing (EVAS) procedure as a possible tool to diagnose EVAS graft infection and differentiate from postimplantation syndrome. Materials and Methods: Eight consecutive male patients (median age 78 years) scheduled for elective EVAS were included in the prospective study (ClinicalTrials.gov identifier NCT02349100). FDG-PET/CT scans were performed in all patients before the procedure and 6 weeks after EVAS. The abdominal aorta was analyzed in 4 regions: suprarenal, infrarenal neck, aneurysm sac, and iliac. The following parameters were obtained for each region: standard uptake value (SUV), tissue to background ratio (TBR), and visual examination of FDG uptake to ascertain its distribution. Demographic data were obtained from medical files and scored based on reporting standards. Results: Visual examination showed no difference between pre- and postprocedure FDG uptake, which was homogenous. In the suprarenal region no significant pre- and postprocedure differences were observed for the SUV and TBR parameters. The infrarenal neck region showed a significant decrease in the SUV and no significant decrease in the TBR. The aneurysm sac and iliac regions both showed a significant decrease in SUV and TBR between the pre- and postprocedure scans. Conclusion: Physiological FDG uptake after EVAS was stable or decreased with regard to the preprocedure measurements. Future research is needed to assess the applicability and cutoff values of FDG-PET/CT scanning to detect endograft infection after EVAS.

Renal artery wall 18F-NaF activity and glomerular filtration rate: an exploratory analysis in a high cardiovascular risk population.

Atherosclerotic plaque molecular imaging with F-sodium fluoride (NaF) PET with computed tomography (PET-CT) may identify active unstable microcalcification. We sought to explore renal arteries calcification activity in a group of high cardiovascular (CV) risk subjects without manifest CV disease. High CV risk hypertensive individuals from a single centre were prospectively scanned with F-NaF-PET-CT in major vascular territories. Renal arterial wall activity was retrospectively analysed and expressed as the ratio between maximum standard uptake value in the lesion and mean blood pool activity in the superior vena cava [tissue-to-background ratio (TBR)]. We explored renal artery wall F-NaF activity's association to CV risk factors and renal function. Mean age was 64 ± 8.6 years, 56% male, 96% Caucasian and 24% had chronic kidney disease (CKD) (n = 25). Six individuals (24%) showed renal artery wall radiotracer uptake (TBR 1.4 ± 0.4); these subjects were heavier, had higher triglycerides, high-sensitivity C-reactive protein and predicted CV risk (SCORE) compared to the remaining cohort (P < 0.05 for all comparisons). There was a trend toward higher F-NaF uptake in other major vessels and increased thoracic fat volume in subjects with renal artery wall uptake. Glomerular filtration rate (GFR) was lower in subjects with positive renal plaques (93.0 ± 29.7 vs. 65.0 ± 19.7 ml/min, P = 0.04). Renal artery radiotracer uptake and eGFR were inversely correlated (r = -0.42, P = 0.04). In a high CV risk group without manifest CV disease, higher renal artery wall F-NaF activity is associated with superior predicted CV risk and lower GFR.

Preliminary Findings from 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Acute Aortic Syndrome

Introduction: Acute aortic syndrome (AAS) encompasses intramural haematoma, aortic dissection and penetrating aortic ulcer. Risk prediction following these conditions remains a challenge. 18F-Sodium Fluoride positron emission tomography / computed tomography (18F-NaF PET/CT) is a novel technique that detects microscopic vascular calcification beyond the resolution of CT alone. In abdominal aortic aneurysms, 18F-NaF PET/CT predicts aneurysm growth and risk of rupture or repair.1 This study aims to examine the utility of 18F-NaF PET/CT in acute aortic syndrome. Methods: Patients with a new diagnosis of AAS and those under surveillance for established acute aortic syndrome were prospectively recruited. The new diagnosis group had 18F-NaF PET/CT within 6 weeks of presentation. Peak radiotracer binding was measured from the aortic root to the aortic bifurcation. Uptake was corrected for background blood-pool activity to obtain a tissue-to-background ratio (TBR). 18F-NaF PET/CT was explored in relation to disease- and patient-related characteristics. ANOVA and linear regression were used for categorical and continuous variables respectively (*=p< 0.001). Results: A total of 3072 TBR measurements were made from 22 patients of median (range) age 65(38-75) years. Thirteen patients had aortic dissection, six had intramural haematoma and three a penetrating aortic ulcer. Substantially increased 18F-NaF binding was seen in all three pathologies (Figure 1): (TBR[95% CI]: 1.82[1.79-1.85] v 1.71[1.68-1.75]* v 2.13[2.02-2.25]*). 18F-NaF uptake was similar in the eight patients with a new diagnoses and 14 with established diagnoses, (TBR 1.83[1.79-1.86] v 1.85[1.82-1.90]; p=0.89). Sixteen patients with Stanford type-B disease had increased radiotracer uptake compared to six with type-A disease (TBR 1.88[1.84-1.91] v 1.75[1.71-1.80]*). Increased 18F-NaF was seen with advancing age*. No difference in radiotracer binding was seen between the 18 men and 4 women (TBR 1.84[1.81-1.87] v 1.84[1.79-1.88], p=0.697) (Figure 2). 18F-NaF uptake was independent of aortic diameter (>32mm v < 32mm: TBR 1.77[1.74-1.80] v 1.86[1.81-1.93];p=0.08), and was associated with increased calcium burden (Agatston score >1600 v < 1600: TBR 2.06[2.01-2.11] v 1.81[1.78-1.85]*). Individuals with endovascular repair (TEVAR: n=2) had aortic remodelling on CT. This group had reduced 18F-NaF uptake (TEVAR v no TEVAR: TBR 1.58[1.56-1.60] v 1.88[1.85-1.91]*). Conclusion: These novel data characterise the relationship between 18F-Sodium Fluoride PET/CT and acute aortic syndrome for the first time. 18F-NaF uptake was increased in all three sub-pathologies. Highest radiotracer binding was seen in penetrating aortic ulcers. 18F-NaF binding was independent of aortic diameter. 18F-NaF PET/CT may also detect aortic remodelling following endovascular repair.Fig 218F-Sodium Fluoride uptake in relation to disease- and patient-related characteristics.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Disclosure: Nothing to disclose

Accuracy of PET/CT in the Diagnosis of Vascular Graft Infections

Introduction - Vascular graft infections (VGI) have an incidence of 1 to 6 %. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) has emerged as a new tool to replace nuclear scintigraphy. However, its clinical reliability is still unknown. The aim of this study was to evaluate the diagnostic accuracy of FDG-PET/CT in a population with suspected VGI and to validate the quantitative value of diagnostic parameters. Methods - This is a retrospective cohort study. FDG-PET/CT was performed in 37 patients with suspected VGI between 2013 and 2017. A reliable culture was obtained in 25 of them and were finally included in the study. VGI was considered proven only in case of a positive culture (blood, peri-graft collections or graft samples. Diagnostic accuracy was assessed comparing culture results (gold standard) with FDG-PET/CT values. We assessed maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual parameters (FDG distribution patterns and visual grading scale) in the final confirmation of the diagnosis of AGI. Receiver operating characteristics (ROC) curves were used to assess the ability of SUVmax and TBR to identify the presence and absence of VGI. Results - The mean age was 64.32 ± 16.75 years, 72% were males. Cultures were positive in 20/25 patients. FDG-PET/CT was considered positive in 19/25 patients. Surgery was performed in 13/25 patients. Mortality was 24% (6/25 patients). The most frequent microorganism was Staphylococcus aureus (9/13 patients). All these patients were followed with long-term antibiotic treatment until negativization of tests including FDG-PET / CT. Mean SUVmax was 6.4 ± 3.41 and TBR 2.14 ± 0.5 in all cases. For positives cultures the mean SUVmax was 7.34 ± 3.3 with a TBR 3.73 ±1.7. In the ROC analysis, the area under the curve for SUVmax was 0.56 (95% CI: 0.30-0.84) and for TBR was 0.53 (95% CI:0.27-0.78). A SUVmax cut off point of 4.5 yielded a 91,7% Sensitivity (Sens) and 50% Specificity (Spec). A TBR cut off point of 2.9 yielded 58% Sens and a 60% Spec with a positive predictive value of 73.68% and negative predictive value of 83.33%. Conclusion - FDG-PET/CT may be a useful tool in the diagnosis and surveillance of VGI. Nevertheless, the accuracy of quantitative parameters is jeopardized by the uncertainty of gold standard based on microbiology data. Further and larger registers with standardized measurements are needed to establish a more reliably parameters, necessary to take difficult decisions in this kind of patients. References-Sah BR, Husmann L, Mayer D, Scherrer A, Rancic Z, Puippe G, Weber R, Hasse B; VASGRA Cohort. Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections. Eur J Vasc Endovasc Surg. 2015 Apr;49(4):455-64.-Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, de Borst GJ, Zeebregts CJ. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015 Apr;61(4):965-71.

FDG-PET/CT as a diagnostic tool in vascular graft infection: a systematic review and meta-analysis

Vascular graft infection (VGI) in central grafts is a rare but dreaded complication with a high mortality. Several imaging modalities are employed, all with pros and cons. Computed tomography is the standard, but lacks sensitivity for low-grade infections. There is still no consensus regarding the diagnostic modality of choice. The study objective was to assess the role of combined positron emission tomography and computed tomography with fluorodeoxyglucose (FDG-PET/CT) in the diagnostic workup of VGI in central grafts. A systematic review was conducted according to the PRISMA guidelines through a search in Embase, PubMed, and Cochrane databases. Meta-analysis on accuracy measures was carried out with random effects models for three parameters: focal uptake, visual grading scale (VGS), and maximum standardized uptake value (SUVmax). Heterogeneity among studies was assessed with the I-squared test. A total of 307 studies were identified and 9 were eligible for inclusion. The pooled estimates for sensitivity and specificity for focal uptake were 90.6% (95% CI 81.7–99.4%) and 82.8% (95% CI 71.3–94.3%), respectively, for VGS 86.8% (95% CI 59.3–100%) and 69.4% (95% CI 39.9–98.9%), respectively, for SUVmax 92.8% (95% CI 83.2–100%) and 69.7% (95% CI 52.4–86.9%), respectively. A single study employed tissue-to-background ratio (TBR) and found sensitivity and specificity of 71.8% (95% CI 54.6–84.4%) and 70.4% (95% CI 51.5–84.2%), respectively. According to this systematic review and meta-analysis, FDG-PET/CT performs well especially when using focal versus diffuse FDG uptake to diagnose VGI.

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography

BackgroundLipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification. MethodsWe recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Québec City, Canada. In a second group of individuals with high (≥75 nmol/L, n = 27) or low (<75 nmol/L, n = 28) Lp(a) levels, 18F-sodium fluoride positron emission tomography/computed tomography was performed to determine the difference in mean tissue-to-background ratio (TBR) of the aortic valve. ResultsPatients with CAVS had 62.0% higher Lp(a) (median = 28.7, interquartile range [8.2-116.6] vs 10.9 [3.6-28.8] nmol/L, P < 0.0001), 50% higher OxPL-apolipoprotein-B (2.2 [1.3-6.0] vs 1.1 [0.7-2.6] nmol/L, P < 0.0001), and 69.9% higher OxPL-apolipoprotein(a) (7.3 [1.8-28.4] vs 2.2 [0.8-8.4] nmol/L, P < 0.0001) levels compared with individuals without CAVS (all P < 0.0001). Individuals without CAVS but elevated Lp(a) had 40% higher mean TBR compared with individuals with low Lp(a) levels (mean TBR = 1.25 ± 0.23 vs 1.15 ± 0.11, P = 0.02). ConclusionsElevated Lp(a) and OxPL levels are associated with prevalent CAVS in patients studied in an echocardiography laboratory setting. In individuals with elevated Lp(a), evidence of aortic valve microcalcification by 18F-sodium fluoride positron emission tomography/computed tomography is present before the development of clinically manifested CAVS.

Hybrid PET/CT and PET/MRI imaging of vulnerable coronary plaque and myocardial scar tissue in acute myocardial infarction

BackgroundFollowing an acute coronary syndrome, combined CT and PET with 18F-NaF can identify coronary atherosclerotic plaques that have ruptured or eroded. However, the processes behind 18F-NaF uptake in vulnerable plaques remain unclear. Methods and ResultsTen patients with STEMI were scanned after 18F-NaF injection, for 75 minutes in a Siemens PET/MR scanner using delayed enhancement (LGE). They were then scanned in a Siemens PET/CT scanner for 10 minutes. Tissue-to-background ratio (TBR) was compared between the culprit lesion in the IRA and remote non-culprit lesions in an effort to independently validate prior studies. Additionally, we performed a proof-of-principle study comparing TBR in scar tissue and remote myocardium using LGE images and PET/MR or PET/CT data. From the 33 coronary lesions detected on PET/CT, TBRs for culprit lesions were higher than for non-culprit lesions (TBR = 2.11 ± 0.45 vs 1.46 ± 0.48; P < 0.001). Interestingly, the TBR measured on the PET/CT was higher for infarcted myocardium than for remote myocardium (TBR = 0.81 ± 0.10 vs 0.71 ± 0.05; P = 0.003). These results were confirmed using the PET/MR data (TBR = 0.81 ± 0.10 for scar, TBR = 0.71 ± 0.06 for healthy myocardium, P = 0.03). ConclusionsWe confirmed the potential of 18F-NaF PET/CT imaging to detect vulnerable coronary lesions. Moreover, we demonstrated proof-of-principle that 18F-NaF concurrently detects myocardial scar tissue.

Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia

Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P<.001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P=.02 and P<.001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P=.05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P=.03 and P=.02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P<.001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.

Textural features of 18F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection

BackgroundThe clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography scanning (PET) has been suggested to play a pivotal role, an evidence-based interpretation is lacking. The objective of this retrospective study was to examine the feasibility and utility of 18F-FDG uptake heterogeneity characterized by textural features to diagnose AGI.MethodsThirty patients with a history of aortic graft reconstruction who underwent 18F-FDG PET/CT scanning were included. Sixteen patients were suspected to have an AGI (group I). AGI was considered proven only in the case of a positive bacterial culture. Positive cultures were found in 10 of the 16 patients (group Ia), and in the other six patients, cultures remained negative (group Ib). A control group was formed of 14 patients undergoing 18F-FDG PET for other reasons (group II). PET images were assessed using conventional maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual grading scale (VGS). Additionally, 64 different 18F-FDG PET based textural features were applied to characterize 18F-FDG uptake heterogeneity. To select candidate predictors, univariable logistic regression analysis was performed (α = 0.16). The accuracy was satisfactory in case of an AUC > 0.8.ResultsThe feature selection process yielded the textural features named variance (AUC = 0.88), high grey level zone emphasis (AUC = 0.87), small zone low grey level emphasis (AUC = 0.80), and small zone high grey level emphasis (AUC = 0.81) most optimal for distinguishing between groups I and II. SUVmax, TBR, and VGS were also able to distinguish between these groups with AUCs of 0.87, 0.78, and 0.90, respectively. The textural feature named short run high grey level emphasis was able to distinguish group Ia from Ib (AUC = 0.83), while for the same task the TBR and VGS were not found to be predictive. SUVmax was found predictive in distinguishing these groups, but showed an unsatisfactory accuracy (AUC = 0.75).ConclusionTextural analysis to characterize 18F-FDG uptake heterogeneity is feasible and shows promising results in diagnosing AGI, but requires additional external validation and refinement before it can be implemented in the clinical decision-making process.

Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer 68Ga-Pentixafor for PET.

68Ga-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of 68Ga-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of 125I-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of 68Ga-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively; P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced 125I-pentixafor uptake in atherosclerotic plaques by approximately 40%. 125I-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r2 = 0.61; P < 0.05). Conclusion:68Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to 18F-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.

Use of somatostatin receptor PET to differentiate between high-risk and low-risk atherosclerotic lesions: a prospective clinical study

BackgroundInflammation drives atherosclerotic plaque rupture that underlies most myocardial infarctions and strokes. Upregulation of somatostatin receptor subtype-2 (SST2) occurs on the cell surface of activated macrophages, offering a potential imaging target for tracking vascular inflammation. We tested the hypothesis that SST2 PET-CT imaging with 68Ga-DOTATATE can detect high-risk carotid and coronary plaque inflammation. We then compared its efficacy with 18F-fludeoxyglucose (18F-FDG), which has limited use in coronary imaging. MethodsProspective sequential 68Ga-DOTATATE PET and 18F-FDG PET imaging, plus CT angiography, were performed in 42 patients with either a recent cardiovascular event (within 3 months of imaging) or stable atherosclerosis, and at least 30% carotid or coronary artery stenosis. Images were analysed, with investigators masked to clinical details, to derive median (IQR) maximum arterial tissue-to-background ratio (TBR). Arterial TBRs were statistically evaluated against clinical and biochemical data, as well as CT-derived plaque morphology. Findings70 carotid arteries and 230 coronary segments were included. 24 patients (57%) had a recent cardiovascular event. 68Ga-DOTATATE TBR (1·98 [1·67–2·14]) was higher in symptomatic carotid arteries than in contralateral arteries (1·77 [1·46–2·08], p=0·0031) and asymptomatic plaques (1·49 [1·36–1·66], p=0·0012). 18F-FDG TBR was also higher on the symptomatic side (1·68 [1·49–1·97] vs 1·51 [1·44–1·80], p=0·0081). The two PET tracers were moderately correlated (r=0·40, p=0·0007). Coronary SST2 signals were visible in all patients, but high myocardial muscle 18F-FDG uptake was prohibitive in 27 patients (64%). Culprit coronary arteries had higher 68Ga-DOTATATE TBR (2·91 [2·69–4·08]) than the highest non-culprit segment (2·61 [1·94–3·01], p=0·0078), stable stented (2·00 [1·51–2·70], p=0·0063), and calcified (1·64 [1·33–2·04], p<0·0001) plaques. SST2 signal from culprit and high-risk coronary arteries was correlated with total cholesterol (r=0·44, p=0·042). InterpretationWe have shown that measurement of vascular inflammation with SST2 PET is feasible and differentiates high-risk and low-risk carotid and coronary lesions. High target specificity, low myocardial binding, and lower cost owing to generator-production give advantage to 68Ga-DOTATATE over 18F-FDG for atherosclerosis imaging. Correlations with 18F-FDG TBR and serum cholesterol further support the vascular SST2 signal as a potential prognostic biomarker to identify patients most at risk of future cardiovascular events. FundingWellcome Trust.

Differential FDG-PET Uptake Patterns in Uninfected and Infected Central Prosthetic Vascular Grafts

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been suggested as a means to detect vascular graft infections. However, little is known about the typical FDG uptake patterns associated with synthetic vascular graft implantation. The aim of the present study was to compare uninfected and infected central vascular grafts in terms of various parameters used to interpret PET images. From 2007 through 2013, patients in whom a FDG-PET scan was performed for any indication after open or endovascular central arterial prosthetic reconstruction were identified. Graft infection was defined as the presence of clinical or biochemical signs of graft infection with positive cultures or based on a combination of clinical, biochemical, and imaging parameters (other than PET scan data). All other grafts were deemed uninfected. PET images were analyzed using maximum systemic uptake value (SUVmax), tissue to background ratio (TBR), visual grading scale (VGS), and focality of FDG uptake (focal or homogenous). Twenty-seven uninfected and 32 infected grafts were identified. Median SUVmax was 3.3 (interquartile range [IQR] 2.0-4.2) for the uninfected grafts and 5.7 for the infected grafts (IQR 2.2-7.8). Mean TBR was 2.0 (IQR 1.4-2.5) and 3.2 (IQR 1.5-3.5), respectively. On VGS, 44% of the uninfected and 72% of the infected grafts were judged as a high probability for infection. Homogenous FDG uptake was noted in 74% of the uninfected and 31% of the infected grafts. Uptake patterns of uninfected and infected grafts showed a large overlap for all parameters. The patterns of FDG uptake for uninfected vascular grafts largely overlap with those of infected vascular grafts. This questions the value of these individual FDG-PET-CT parameters in identifying infected grafts.