Guideline Adherence as an Indicator of PET Scan Overuse in an Italian Teaching Hospital: An Observational Study.

BACKGROUND: Evidence of inappropriate overuse and underuse of medical procedures has been documented in modern healthcare systems around the world. Excessive use of health services can contribute to a rapid increase in healthcare costs and harm the patient physically and psychologically; conversely, underuse can lead to the inability to provide effective treatments when clinically indicated. OBJECTIVE: The study's aim is twofold: a) to measure the appropriateness of PET prescription in a cohort of patients, offering empirical evidence of overuse of health care services; b) to evaluate how the overuse of PET could affect public health expenditure and, consequently, the system's financial sustainability. METHODS: In this observational study, we have analyzed prospectively and retrospectively health patient records who underwent 18F-FDG PET/TC scan at the Nuclear Medicine Department of the University Hospital Mater Domini in Catanzaro (Italy) from 29/09/2022 to 10/02/2023. Patients' diagnostic questions have been defined as appropriate, not completely appropriate and completely inappropriate according to the 18F-FDG PET/CT recommendations defined by the "Conditions of Supply and Indications of Prescriptive Appropriateness of Italian NHS (National Health Systems)" published in the Official Gazette no. 15 of 20 January 2016 (Decree 9 December 2015) and by the AIMN (Italian Association of Nuclear Medicine) guidelines. RESULTS: We gathered data from 500 oncological patients (242 males and 258 females). The results show that 423/500 of patients' prescriptions were appropriate, while 77/500 of patients' prescriptions were completely inappropriate (63/77) or not completely appropriate (14/77). CONCLUSION: Analysis showed a not complete adherence to national guidelines and no shared decision-making approach.

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects.

BACKGROUND: Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects. METHODS: We aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26). RESULTS: Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association. CONCLUSIONS: Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

Computed tomography: Diagnostic detection of complete pericardial agenesis: A case report.

Congenital complete absence of the pericardium is a rare condition, often difficult to diagnose due to its incidental discovery or nonspecific clinical manifestations. Instrumental investigations commonly used as initial approaches, such as chest radiography and electrocardiogram, are often insufficient. Echocardiography is an imaging technique that is used for the initial evaluation of pericardial diseases. However, echocardiography does not offer a physiological anatomical delineation of the pericardium and can be affected by operator dependency, acoustic and nontraditional imaging windows. Therefore, accurate imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) are required for correct diagnosis. We present a case of a symptomatic patient with complete pericardial agenesis diagnosed on angio-CT. This case can contribute to highlighting the importance of CT as a comprehensive imaging method in diagnosis, despite MRI being the gold standard in pericardial disease assessment.

The Role of Imaging of Lymphatic System to Prevent Cancer Related Lymphedema.

Lymphedema is a progressive chronic condition affecting approximately 250 million people worldwide, a number that is currently underestimated. In Western countries, the most common form of lymphedema of the extremities is cancer-related and less radical surgical intervention is the main option to prevent it. Standardized protocols in the areas of diagnosis, staging and treatment are strongly required to address this issue. The aim of this study is to review the main diagnostic methods, comparing new emerging procedures to lymphoscintigraphy, considered as the golden standard to date. The roles of Magnetic Resonance Lymphangiography (MRL) or indocyanine green ICG lymphography are particularly reviewed in order to evaluate diagnostic accuracy, potential associations with lymphoscintigraphy, and future directions guided by AI protocols. The use of imaging to treat lymphedema has benefited from new techniques in the area of lymphatic vessels anatomy; these perspectives have become of value in many clinical scenarios to prevent cancer-related lymphedema.

Primary large B-cell lymphoma involving the cerebellopontine angle mimic acoustic schwannoma: Role of MR Spectroscopy in differential diagnosis. A case report.

Primary central nervous system (CNS) lymphoma is a very rare aggressive non-Hodgkin disease that originates in CNS (brain, leptomeninges, spinal cord, or eyes). It seems to have increased over the last two decades in both immunocompromised and immunocompetent patients. Primary large B-cell lymphoma involving the cerebellopontine angle (CPA) is extremely rare: only 15 cases of large B-cell lymphoma of the CPA have been reported worldwide; based on our knowledge, no cases studied with MR Spectroscopy. Primary large B-cell lymphoma of the CPA must be differentiated from other cerebellopontine angle diseases, such as acoustic neuroma and meningioma. An early and accurate diagnosis of this neoplasm is necessary for the best management because it is a radiosensitive and chemosensitive tumor. Herein, we report a rare case of B-cell lymphoma involving the left CPA in a 65-year-old man who presented with 3 months of hearing loss on the left, illustrated by MR and TC imaging, highlighting how the MR Spectroscopy, thanks to their greater specificity, is decisive in achieving the correct diagnosis of primary lymphoma and differentiating it from acoustic schwannoma or meningioma. Therefore, in the suspicion of a malignant heteroplastic lesion of the CPA, we suggest including Spectroscopy in the MR study protocol.

Role of Nuclear Sentinel Lymph Node Mapping Compared to New Alternative Imaging Methods.

With the emergence of sentinel node technology, many patients can be staged histopathologically using lymphatic mapping and selective lymphadenectomy. Structural imaging by using US, CT and MR permits precise measurement of lymph node volume, which is strongly associated with neoplastic involvement. Sentinel lymph node detection has been an ideal field of application for nuclear medicine because anatomical data fails to represent the close connections between the lymphatic system and regional lymph nodes, or, more specifically, to identify the first draining lymph node. Hybrid imaging has demonstrated higher accuracy than standard imaging in SLN visualization on images, but it did not change in terms of surgical detection. New alternatives without ionizing radiations are emerging now from "non-radiological" fields, such as ophthalmology and dermatology, where fluorescence or opto-acoustic imaging, for example, are widely used. In this paper, we will analyze the advantages and limits of the main innovative methods in sentinel lymph node detection, including innovations in lymphoscintigraphy techniques that persist as the gold standard to date.

18F-PSMA-1007 salivary gland dosimetry: comparison between different methods for dose calculation and assessment of inter- and intra-patient variability.

Objective. Simplified calculation approaches and geometries are usually adopted for salivary glands (SGs) dosimetry. Our aims were (i) to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following [18F]-PSMA-1007 injection, and (ii) to assess the AD variation across patients and single SG components. Approach. Five patients with prostate cancer underwent sequential positron-emission tomography/computed tomography (PET/CT) acquisitions of the head and neck, 0.5, 2 and 4 h after [18F]-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PET images were used to derive Time-Integrated Activity Coefficients. Average ADs to single SG components or total SG (tSG) were calculated with the following methods: (i) direct Monte Carlo simulation with GATE/GEANT4 considering radioactivity in the entire PET/CT field-of-view (MC) or in the SGs only (MCsgo); (ii) spherical model (SM) of OLINDA/EXM 2.1, adopting either patient-specific or standard ICRP89 organ masses (SMstd); (iii) ellipsoidal model (EM); (iv) MIRD approach with organS-factors from OLINDA/EXM 2.1 and OpenDose collaboration, with or without contribution from cross irradiation originating outside the SGs. The maximum percent AD difference across SG components (δmax) and across patients (Δmax) were calculated.Main results. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences ranging between -11.9% and -30.5%).δmaxvalues were never below 25%. The highestδmax(=702%) was obtained with SMstd. Concerning tSG, results within 10% of the MC were obtained only if cross-irradiation from the remainder of the body or from the remainder of the head was accounted for. The Δmaxranged between 58% and 78% across patients.Significance. Simple geometrical models for SG dosimetry considerably underestimated ADs compared to MC, particularly if neglecting cross-irradiation from neighboring regions. Specific masses of single SG components should always be considered given their large intra- and inter-patient variability.

Radioimmunotherapy of Non-Hodgkin B-cell Lymphoma: An update.

Systemic radioimmunotherapy (RIT) is arguably the most effective and least toxic anticancer treatment for non-Hodgkin lymphoma (NHL). In treatment-naïve patients with indolent NHL, the efficacy of a single injection of RIT compares with that of multiple cycles of combination chemotherapy. However, 20 years following the approval of the first CD20-targeting radioimmunoconjugates 90Y-Ibritumomab-tiuxetan (Zevalin) and 131I-tositumomab (Bexxar), the number of patients referred for RIT in western countries has dramatically decreased. Notwithstanding this, the development of RIT has continued. Therapeutic targets other than CD20 have been identified, new vector molecules have been produced allowing for faster delivery of RIT to the target, and innovative radionuclides with favorable physical characteristics such as alpha emitters have been more widely available. In this article, we reviewed the current status of RIT in NHL, with particular focus on recent clinical and preclinical developments.

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.

Functional connectivity of the cortico-subcortical sensorimotor loop is modulated by the severity of nigrostriatal dopaminergic denervation in Parkinson's Disease.

To assess if the severity of nigrostriatal innervation loss affects the functional connectivity (FC) of the sensorimotor cortico-striato-thalamic-cortical loop (CSTCL) in Parkinson's Disease (PD), Resting-State functional MRI and 18F-DOPA PET data, simultaneously acquired on a hybrid PET/MRI scanner, were retrospectively analyzed in 39 PD and 16 essential tremor patients. Correlations between posterior Putamen DOPA Uptake (pPDU) and the FC of the main CSTCL hubs were assessed separately in the two groups, analyzing the differences between the two groups by a group-by-pPDU interaction analysis of the resulting clusters' FC. Unlike in essential tremor, in PD patients pPDU correlated inversely with the FC of the thalamus with the sensorimotor cortices, and of the postcentral gyrus with the dorsal cerebellum, and directly with the FC of pre- and post-central gyri with both the superior and middle temporal gyri and the paracentral lobule, and of the caudate with the superior parietal cortex. The interaction analysis confirmed the significance of the difference between the two groups in these correlations. In PD patients, the post-central cortex FC, in the clusters correlating directly with pPDU, negatively correlated with both UPDRS motor examination score and Hoehn and Yahr stage, independent of the pPDU, suggesting that these FC changes contribute to motor impairment. In PD, nigrostriatal innervation loss correlates with a decrease in the FC within the sensorimotor network and between the sensorimotor network and the superior temporal cortices, possibly contributing to motor impairment, and with a strengthening of the thalamo-cortical FC, that may represent ineffective compensatory phenomena.

Unespected dectection of unruptured brain arteriovenous malformation with 18F-DOPA PET/MR.

Unruptured brain arteriovenous malformations (AVM) have a heterogeneous clinical presentation, mainly related to the presence of intracerebral hemorrhage. We report the diagnosis of AVM in a patient with Parkinson's disease (PD), who undergone positron emission tomography/magnetic resonance imaging (PET/MRI) molecular brain imaging with fluorine-18-dihydroxyphenylalanine (18F-DOPA). This case suggests that AVM may be occasionally recognized in molecular imaging studies using positron-emitting amino acids. Magnetic resonance imaging with susceptibility-weighted imaging (SWI) sequences and 3D time of flight (TOF) reconstruction may contribute to manage patients with AVM.

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.

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.

Tailored Molecular Imaging of Pheochromocytoma and Paraganglioma: Which Tracer and When.

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neoplasms that fall within the category of neuroendocrine tumors. In the last decade, their diagnostic algorithm has been modified to include the evaluation of molecular pathways, genotype, and biochemical phenotype, in order to correctly interpret anatomical and functional imaging results and tailor the best therapeutic choices to patients. More specifically, the identification of germline mutations has led to a three-way cluster classification: pseudo-hypoxic cluster, cluster of kinase receptor signaling and protein translation pathways, and cluster of Wnt-altered pathway. In this context, functional imaging gained a crucial role in the management of these patients in agreement with the ever-growing concept of personalized medicine. In this paper, we provide an overview of three specific molecular pathways targeted by positron-emitting tracers to image PCCs and PGLs: catecholamine metabolism, somatostatin receptors, and glucose uptake. Finally, we recommend different flow charts for use in the selection of tracers for specific clinical scenarios, based on sporadic/inherited tumor and known/unknown mutation status.

MAFLD progression contributes to altered thalamus metabolism and brain structure.

Metabolic associated fatty liver disease (MAFLD), commonly known as non-alcoholic fatty liver disease, represents a continuum of events characterized by excessive hepatic fat accumulation which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and in some severe cases hepatocellular carcinoma. MAFLD might be considered as a multisystem disease that affects not only the liver but involves wider implications, relating to several organs and systems, the brain included. The present study aims to investigate changes associated with MAFLD-induced alteration of thalamic metabolism in vivo. DIAMOND (Diet-induced animal model of non-alcoholic fatty liver disease) mice were fed a chow diet and tap water (NC NW) or fat Western Diet (WD SW) for up to 28 weeks. At the baseline and weeks 4, 8, 20, 28 the thalamic neurochemical profile and total cerebral brain volume were evaluated longitudinally in both diet groups using 1H-MRS. To confirm the disease progression, at each time point, a subgroup of animals was sacrificed, the livers excised and placed in formalin. Liver histology was assessed and reviewed by an expert liver pathologist. MAFLD development significantly increases the thalamic levels of total N-acetylaspartate, total creatine, total choline, and taurine. Furthermore, in the WD SW group a reduction in total cerebral brain volume has been observed (p < 0.05 vs NC NW). Our results suggest that thalamic energy metabolism is affected by MAFLD progression. This metabolic imbalance, that is quantifiable by 1H-MRS in vivo, might cause structural damage to brain cells and dysfunctions of neurotransmitter release.

FDG-CT/PET false positive case in hip prosthesis: a clue to avoid error.

A 62 years old woman 6 months after left total hip prosthesis referred to our institution for persistent pain and warm, stiff, and swollen joint. 18F-FDG CT/PET Images showed an intense focal uptake corresponding to the external margin of inter-trochanteric region of prosthesis and inside the stem inferiorly, but common decision was to reconstruct PET images without attenuation correction and now showed a complete and unexpected disappearance of focal and pathological FDG uptake. This case shows the potential propagation of CT artifacts into PET emission data close to metal implants and should be taken in account together to SUV values.

The Role of Molecular Imaging in a Muscle-Invasive Bladder Cancer Patient: A Narrative Review in the Era of Multimodality Treatment.

Diagnostic imaging in bladder cancer plays an important role since it is needed from pretreatment staging to follow-up, but a morphological evaluation performed with both CT and MRI showed low sensitivities and specificities in detecting pathologic lymph nodes, due to the occurrence of false positive results. Implementation of functional information provided by PET/CT could be a determinant in the management of patients with muscle-invasive bladder cancer. A focus on the role of 18F-FDG PET/CT and alternative tracers in patients with muscle-invasive bladder cancer is provided in this analysis in order to outline its potential applications in staging settings and response evaluation after neoadjuvant chemotherapy.