Impaired insulin-stimulated myocardial glucose metabolic rate is associated with reduced estimated myocardial energetic efficiency in subjects with different degrees of glucose tolerance.

BACKGROUND: Alterations in myocardial mechano-energetic efficiency (MEEi), which represents the capability of the left ventricles to convert the chemical energy obtained by oxidative metabolism into mechanical work, have been associated with cardiovascular disease. Although whole-body insulin resistance has been related to impaired myocardial MEEi, it is unknown the relationship between cardiac insulin resistance and MEEi. Aim of this study was to evaluate the relationship between insulin-stimulated myocardial glucose metabolic rate (MrGlu) and myocardial MEEi in subjects having different degrees of glucose tolerance. METHODS: We evaluated insulin-stimulated myocardial MrGlu using cardiac dynamic positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) combined with euglycemic-hyperinsulinemic clamp, and myocardial MEEi in 57 individuals without history of coronary heart disease having different degrees of glucose tolerance. The subjects were stratified into tertiles according to their myocardial MrGlu values. RESULTS: After adjusting for age, gender and BMI, subjects in I tertile showed a decrease in myocardial MEEi (0.31 ± 0.05 vs 0.42 ± 0.14 ml/s*g, P = 0.02), and an increase in myocardial oxygen consumption (MVO2) (10,153 ± 1375 vs 7816 ± 1229 mmHg*bpm, P < 0.0001) as compared with subjects in III tertile. Univariate correlations showed that insulin-stimulated myocardial MrGlu was positively correlated with MEEi and whole-body glucose disposal, and negatively correlated with waist circumference, fasting plasma glucose, HbA1c and MVO2. In a multivariate regression analysis running a model including several CV risk factors, the only variable that remained significantly associated with MEEi was myocardial MrGlu (ß 0.346; P = 0.01). CONCLUSIONS: These data suggest that an impairment in insulin-stimulated myocardial glucose metabolism is an independent contributor of depressed myocardial MEEi in subjects without history of CHD.

Cross-sectional evaluation of FGD-avid polyostotic fibrous dysplasia: MRI, CT and PET/MRI findings.

A 42-year-old male with left hip pain was diagnosed of several right femoral and tibial bone tumours. All lesions were osteolytic with sclerotic margins. The symptomatic lesion in the proximal femur also showed bone expansion and focal cortical thinning. Whole-body [18F]-fluorodeoxyglucose (FDG) PET/CT and segmental PET/MRI of the left hip and femur were performed for metabolic characterization of the lesions and for biopsy guidance. The lesions showed a heterogenous degree of FDG uptake corresponding to different metabolic stages of the disease. A biopsy of the tumour portion showing the highest FDG uptake revealed a fibrous dysplasia (FD). In conclusion, although generally affecting paediatric and adolescent subjects, polyostotic FD may be detected in the adulthood. Despite the benign nature of the disease, increased glucose metabolism can be seen in some lesions. Hybrid imaging combining morphological and functional information may help guide biopsy and better define the treatment strategy.

Metabolic Syndrome Is Associated With Impaired Insulin-Stimulated Myocardial Glucose Metabolic Rate in Individuals With Type 2 Diabetes: A Cardiac Dynamic 18F-FDG-PET Study.

Metabolic syndrome is a condition characterized by a clustering of metabolic abnormalities associated with an increased risk of type 2 diabetes and cardiovascular disease. An impaired insulin-stimulated myocardial glucose metabolism has been shown to be a risk factor for the development of cardiovascular disease in patients with type 2 diabetes. Whether cardiac insulin resistance occurs in subjects with metabolic syndrome remains uncertain. To investigate this issue, we evaluated myocardial glucose metabolic rate using cardiac dynamic 18F-FDG-PET combined with euglycemic-hyperinsulinemic clamp in three groups: a group of normal glucose tolerant individuals without metabolic syndrome (n = 10), a group of individuals with type 2 diabetes and metabolic syndrome (n = 19), and a group of subjects with type 2 diabetes without metabolic syndrome (n = 6). After adjusting for age and gender, individuals with type 2 diabetes and metabolic syndrome exhibited a significant reduction in insulin-stimulated myocardial glucose metabolic rate (10.5 ± 9.04 µmol/min/100 g) as compared with both control subjects (32.9 ± 9.7 µmol/min/100 g; P < 0.0001) and subjects with type 2 diabetes without metabolic syndrome (25.15 ± 4.92 µmol/min/100 g; P = 0.01). Conversely, as compared with control subjects (13.01 ± 8.53 mg/min x Kg FFM), both diabetic individuals with metabolic syndrome (3.06 ± 1.7 mg/min × Kg FFM, P = 0.008) and those without metabolic syndrome (2.91 ± 1.54 mg/min × Kg FFM, P = 0.01) exhibited a significant reduction in whole-body insulin-stimulated glucose disposal, while no difference was observed between the 2 groups of subjects with type 2 diabetes with or without metabolic syndrome. Univariate correlations showed that myocardial glucose metabolism was positively correlated with insulin-stimulated glucose disposal (r = 0.488, P = 0.003), and negatively correlated with the presence of metabolic syndrome (r = -0.743, P < 0.0001) and with its individual components. In conclusion, our data suggest that an impaired myocardial glucose metabolism may represent an early cardio-metabolic defect in individuals with the coexistence of type 2 diabetes and metabolic syndrome, regardless of whole-body insulin resistance.

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open-label, crossover, active-comparator FIORE trial.

AIM: To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) combined with euglycaemic-hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. MATERIALS AND METHODS: To further investigate the cardioprotective mechanism of sodium-glucose co-transporter-2 inhibitors, we performed a 26-week, randomized, open-label, crossover, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic 18 F-FDG-PET combined with euglycaemic-hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano-energetic efficiency, as well as systolic and diastolic function by echocardiography. RESULTS: Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 [-8.59, -3.55] µmol/min/100 g; P < .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, N-terminal pro b-type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. CONCLUSIONS: The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.

Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET.

BACKGROUND: The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). METHODS: Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. RESULTS: Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12-66) months. Median follow-up from the baseline F-DOPA PET/CT was 48 (range 21-95) months. Overall, 24 (70.6%) and 10 (29.4%) lesions were classified as RN and LP, respectively. LP occurred after a median of 18 (range: 12-30) months from baseline PET. F-DOPA tumor-to-brain ratio (TBR) and relative standardized uptake value (rSUV) increased significantly over time in LP lesions, while remaining stable in RN lesions. The parameter showing the best diagnostic performance was rSUV (accuracy = 94.1% for the optimal threshold of 1.92). In contrast, variations of the longest tumor dimension measured on contrast-enhancing MRI did not distinguish between RN and LP. CONCLUSION: F-DOPA PET has a high diagnostic accuracy for assessing the long-term evolution of brain metastases following SRS.

Not all that glitters is COVID! Differential diagnosis of FDG-avid interstitial lung disease in low-prevalence regions.

Coronavirus disease-19 (COVID-19) is only one of the many possible infectious and non-infectious diseases that may occur with similar imaging features in patients undergoing [18F]-fluorodeoxyglucose (18FDG) monitoring, particularly in the most fragile oncologic patients. We briefly summarise some key radiological elements of differential diagnosis of interstitial lung diseases which, in our opinion, could be extremely useful for physicians reporting 18FDG PET/CT scans, not only during the COVID-19 pandemic, but also for their normal routine activity.

Reduction in Global Myocardial Glucose Metabolism in Subjects With 1-Hour Postload Hyperglycemia and Impaired Glucose Tolerance.

OBJECTIVE: Impaired insulin-stimulated myocardial glucose uptake has occurred in patients with type 2 diabetes with or without coronary artery disease. Whether cardiac insulin resistance is present remains uncertain in subjects at risk for type 2 diabetes, such as individuals with impaired glucose tolerance (IGT) or those with normal glucose tolerance (NGT) and 1-h postload glucose ≥155 mg/dL during an oral glucose tolerance test (NGT 1-h high). This issue was examined in this study. RESEARCH DESIGN AND METHODS: The myocardial metabolic rate of glucose (MRGlu) was measured by using dynamic 18F-fluorodeoxyglucose positron emission tomography combined with a euglycemic-hyperinsulinemic clamp in 30 volunteers without coronary artery disease. Three groups were studied: 1) those with 1-h postload glucose <155 mg/dL (NGT 1-h low) (n = 10), 2) those with NGT 1-h high (n = 10), 3) and those with IGT (n = 10). RESULTS: After adjusting for age, sex, and BMI, both subjects with NGT 1-h high (23.7 ± 6.4 mmol/min/100 mg; P = 0.024) and those with IGT (16.4 ± 6.0 mmol/min/100 mg; P < 0.0001) exhibited a significant reduction in global myocardial MRGlu; this value was 32.8 ± 9.7 mmol/min/100 mg in subjects with NGT 1-h low. Univariate correlations showed that MRGlu was positively correlated with insulin-stimulated whole-body glucose disposal (r = 0.441; P = 0.019) and negatively correlated with 1-h (r = -0.422; P = 0.025) and 2-h (r = -0.374; P = 0.05) postload glucose levels, but not with fasting glucose. CONCLUSIONS: This study shows that myocardial insulin resistance is an early defect that is already detectable in individuals with dysglycemic conditions associated with an increased risk of type 2 diabetes, such as IGT and NGT 1-h high.

Volumetric assessment of recurrent or progressive gliomas: comparison between F-DOPA PET and perfusion-weighted MRI.

PURPOSE: To compare the diagnostic information obtained with 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) PET and relative cerebral blood volume (rCBV) maps in recurrent or progressive glioma. METHODS: All patients with recurrent or progressive glioma referred for F-DOPA imaging at our institution between May 2010 and May 2014 were retrospectively included, provided that macroscopic disease was visible on conventional MRI images and that rCBV maps were available for comparison. The final analysis included 50 paired studies (44 patients). After image registration, automatic tumour segmentation of both sets of images was performed using the average signal in a large reference VOI including grey and white matter multiplied by 1.6. Tumour volumes identified by both modalities were compared and their spatial congruence calculated. The distances between F-DOPA uptake and rCBV hot spots, tumour-to-brain ratios (TBRs) and normalized histograms were also computed. RESULTS: On visual inspection, 49 of the 50 F-DOPA and 45 of the 50 rCBV studies were classified as positive. The tumour volume delineated using F-DOPA (F-DOPAvol 1.6) greatly exceeded that of rCBV maps (rCBVvol 1.6). The median F-DOPAvol 1.6 and rCBVvol 1.6 were 11.44 ml (range 0 - 220.95 ml) and 1.04 ml (range 0 - 26.30 ml), respectively (p < 0.00001). Overall, the median overlapping volume was 0.27 ml, resulting in a spatial congruence of 1.38 % (range 0 - 39.22 %). The mean hot spot distance was 27.17 mm (±16.92 mm). F-DOPA uptake TBR was significantly higher than rCBV TBR (1.76 ± 0.60 vs. 1.15 ± 0.52, respectively; p < 0.0001). The histogram analysis showed that F-DOPA provided better separation of tumour from background. In 6 of the 50 studies (12 %), however, physiological uptake in the striatum interfered with tumour delineation. CONCLUSION: The information provided by F-DOPA PET and rCBV maps are substantially different. Image interpretation is easier and a larger tumour extent is identified on F-DOPA PET images than on rCBV maps. The clinical impact of such differences needs to be explored in future studies.

Thyro-gastric autoimmunity in patients with differentiated thyroid cancer: a prospective study.

Thyro-gastric autoimmunity has not been previously evaluated in patients with differentiated thyroid cancer (DTC), although its long-term complications may be relevant for the management of DTC patients. We assessed the prevalence of gastric autoimmunity and autoimmune gastritis (AG) in patients with Hashimoto's thyroiditis (HT) and concomitant DTC. Prevalence of parietal cell antibody (PCA) positivity, iron deficiency anemia (IDA), and pernicious anemia (PA) were prospectively assessed in 150 DTC patients referred for radioiodine ablation after total thyroidectomy. Patients were classified as HT (n = 31) and non-HT (n = 119) based on a combination of serological, ultrasonographic, and histological findings. Patients with PCA positivity were subsequently addressed to endoscopy for confirmation of atrophy body gastritis, required for the diagnosis of AG. For all the variables under study, a comparison between groups was made using Fisher's exact test and appropriate parametric and non-parametric tests. PCA positivity was significantly more prevalent in HT than in non-HT patients (12.9 vs 1.6 %, p = 0.017). After Hp eradication, a reversal of PCA positivity was observed in 3/4 patients in the HT group. IDA and PA did not differ significantly between groups. In the HT group, only one patient had endoscopical confirmation of mild gastric corporal atrophy. Gastric autoimmunity shows higher prevalence in patients with DTC and concomitant HT than in patients with DTC alone; however, in most cases, PCA positivity was associated with Hp infection. Furthermore, although previous reports found up to one-third of patients with HT to have associated AG, in our cohort AG was extremely rare.

Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery.

PURPOSE: We assessed the performance of 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR). METHODS: In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart. RESULTS: Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVLmax/Bkgrmax). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %). CONCLUSION: F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR.