PET/CT in thyroid cancer — the importance of BRAF mutations

Thyroid cancer (TC) represents less than 1% of all newly diagnosed malignancies. In some selected cases, with a high clinical suspicion for disease but negative I-131 scan, positron emission tomography/computed tomography (PET) with F-18-Fluorodeoxyglucose (FDG) could be helpful in the detection of disease and the definition of its extent. FDG PET/CT, better if performed after TSH stimulation analogously to patient preparation done for radioiodine scintigraphy, could be useful mainly in the detection of metastatic and recurrent disease since the uptake and diagnostic sensitivity of FDG are increased by TSH stimulation. Recently, the role of oncogenic mutations in the tumorigenesis of TCs has become clearer. Among such mutations, BRAFV600E represents the most common genetic alteration. Mutated BRAF may define a more aggressive papillary carcinoma with poorer prognosis and therefore its analysis has been extensively studied as a rule-in test for thyroid carcinoma. In this paper, we try to outline the possible role of FDG PET/CT in the management of patients with TC and positive BRAF mutations and the impact that it could have on their therapeutic algorithm, in terms of thyroidectomy and radioactive iodine (RAI) therapy

18^{18}F-PSMA-1007 salivary gland dosimetry: Comparison between different methods for dose calculation and assessment of inter- and intra-patient variability

Dosimetry of salivary glands (SGs) is usually implemented using simplified calculation approaches and approximated geometries. Our aims were to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following 18F-PSMA-1007 injection, and to assess the AD variation across patients and single SG components. Five patients with prostate cancer recurrence underwent PET/CT acquisitions of the head and neck, 0.5, 2 and 4 hours after 18F-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PETs 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 (MC) simulation with GATE/GEANT4; 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 organ S-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 ({\delta}max) and across patients ({\Delta}max) were calculated. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences between -14.5% and -30.4%). Using MC, SM and EM, {\delta}max were never below 25% (up to 113%). {\delta}max up to 702% were 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 {\Delta}max ranged between 58% and 78% across patients. Specific masses of single SG components should always be considered given their large intra- and inter- patient variability.Comment: 33 pages, 3 figures, sumbitted to "Physics in Medicine & Biology

Bioinformatics Solutions for Image Data Processing

In recent years, the increasing use of medical devices has led to the generation of large amounts of data, including image data. Bioinformatics solutions provide an effective approach for image data processing in order to retrieve information of interest and to integrate several data sources for knowledge extraction; furthermore, images processing techniques support scientists and physicians in diagnosis and therapies. In addition, bioinformatics image analysis may be extended to support several scenarios, for instance, in cyber-security the biometric recognition systems are applied to unlock devices and restricted areas, as well as to access sensitive data. In medicine, computational platforms generate high amount of data from medical devices such as Computed Tomography (CT), and Magnetic Resonance Imaging (MRI); this chapter will survey on bioinformatics solutions and toolkits for medical imaging in order to suggest an overview of techniques and methods that can be applied for the imaging analysis in medicine

Neuroimaging and Neurolaw: Drawing the Future of Aging

Human brain-aging is a complex, multidimensional phenomenon. Knowledge of the numerous aspects that revolve around it is therefore essential if not only the medical issues, but also the social, psychological, and legal issues related to this phenomenon are to be managed correctly. In the coming decades, it will be necessary to find solutions to the management of the progressive aging of the population so as to increase the number of individuals that achieve successful aging. The aim of this article is to provide a current overview of the physiopathology of brain aging and of the role and perspectives of neuroimaging in this context. The progressive development of neuroimaging has opened new perspectives in clinical and basic research and it has modified the concept of brain aging. Neuroimaging will play an increasingly important role in the definition of the individual's brain aging in every phase of the physiological and pathological process. However, when the process involved in age-related brain cognitive diseases is being investigated, factors that might affect this process on a clinical and behavioral level (genetic susceptibility, risks factors, endocrine changes) cannot be ignored but must, on the contrary, be integrated into a neuroimaging evaluation to ensure a correct and global management, and they are therefore discussed in this article. Neuroimaging appears important to the correct management of age-related brain cognitive diseases not only within a medical perspective, but also legal, according to a wider approach based on development of relationship between neuroscience and law. The term neurolaw, the neologism born from the relationship between these two disciplines, is an emerging field of study, that deals with various issues in the impact of neurosciences on individual rights. Neuroimaging, enhancing the detection of physiological and pathological brain aging, could give an important contribution to the field of neurolaw in elderly where the full control of cognitive and volitional functions is necessary to maintain a whole series of rights linked to legal capacity. For this reason, in order to provide the clinician and researcher with a broad view of the brain-aging process, the role of neurolaw will be introduced into the brain-aging context

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 F-18-fluorodeoxyglucose-positron emission tomography (F-18-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 F-18-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] mu mol/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

Microvascular Invasion in HCC: The Molecular Imaging Perspective

Hepatocellular carcinoma represents the most frequent primary liver tumor; curative options are only surgical resection and liver transplantation. From 1996, Milan Criteria are applied in consideration of patients with cirrhosis and hepatocellular for liver transplantation; nonetheless, more recently, Milan Criteria have been criticized because they appear over conservative. Apart from number and size of lesions and biomarker levels, which already have been associated with poorer prognosis, overall survival and recurrence rates after transplantation are affected also by the presence of vascular invasion. Microvascular invasion suggests a poor prognosis but it is often hard to detect before transplant. Diagnostic imaging and tumor markers may play an important role and become the main tools to define microvascular invasion. In particular, a possible role could be found for computed tomography, magnetic resonance imaging, and positron emission tomography. In this paper, we analyze the possible role of positron emission tomography as a preoperative imaging biomarker capable of predicting microvascular invasion in patients with hepatocellular carcinoma and thus selecting optimal candidates for liver transplantation

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

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