Vincenzo Allegri's research while affiliated with University Hospital of Parma and other places

Simple Summary Neuroendocrine neoplasms’ (NENs) rarity and heterogeneity represent a clinical challenge. Somatostatin receptor (SST) positron emission tomography/computed tomography (PET/CT) availability and different reimbursement policies across countries account for its heterogenous employment on a single-case basis. The aim of this study was to prospectively collect data of the real-life use of and indications for [68Ga-DOTA⁰-1NaI³]octreotide ([68Ga]Ga-DOTANOC) PET/CT in a prospective 5-year electronic archive at a single center. Overall, more than 2000 scans were included. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the trends of [68Ga]Ga-DOTANOC PET/CT use across different clinical indications and primary tumor sites. Abstract The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.

Purpose To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD). Methods We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau181 and t-tauAg, amyloid, and ¹⁸F-FDG PET of five unrelated LD families. Results Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aβ42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer's disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase. Conclusions Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer's disease type.

Aim/Introduction Digital PET/CT allows Q.Clear image reconstruction with different Beta (β) levels. However, no definitive standard β level for [68 Ga]Ga-DOTANOC PET/CT has been established yet. As patient’s body mass index (BMI) can affect image quality, the aim of the study was to visually and semi-quantitatively assess different β levels compared to standard OSEM in overweight patients. Materials and methods Inclusion criteria: (1) patients with NEN included in a prospective CE-approved electronic archive; (2) [68 Ga]Ga-DOTANOC PET/CT performed on a digital tomograph between September2019/March2021; (3) BMI ≥ 25. Images were acquired following EANM guidelines and reconstructed with OSEM and Q.Clear with three β levels (800, 1000, 1600). Scans were independently reviewed by three expert readers, unaware of clinical data, who independently chose the preferred β level reconstruction for visual overall image quality. Semi-quantitative analysis was performed on each scan: SUVmax of the highest uptake lesion (SUVmax-T), liver background SUVmean (SUVmean-L), SUVmax-T/SUVmean-L, Signal-to-noise ratio for both liver (LSNR) and the highest uptake lesion (SNR-T), Contrast-to-noise ratio (CNR). Results Overall, 75 patients (median age: 63 years old [23–87]) were included: pre-obesity sub-group (25 ≤ BMI < 30, n = 50) and obesity sub-group (BMI ≥ 30, n = 25). PET/CT was positive for disease in 45/75 (60.0%) cases (14 obese and 31 pre-obese patients). Agreement among readers’ visual rating was high (Fleiss κ = 0.88) and the β1600 was preferred in most cases (in 96% of obese patients and in 53.3% of pre-obese cases). OSEM was considered visually equal to β1600 in 44.7% of pre-obese cases and in 4% of obese patients. In a minority of pre-obese cases, OSEM was preferred (2%). In the whole population, CNR, SNR-T and LSNR were significantly different (p < 0.001) between OSEM and β1600, conversely to SUVmean-L (not significant). These results were also confirmed when calculated separately for the pre-obesity and obesity sub-groups β800 and β1000 were always rated inferior. Conclusions Q.Clear is a new technology for PET/CT image reconstruction that can be used to increase CNR and SNR-T, to subsequently optimise overall image quality as compared to standard OSEM. Our preliminary data on [68 Ga]Ga-DOTANOC PET/CT demonstrate that in overweight NEN patients, β1600 is preferable over β800 and β1000. Further studies are warranted to validate these results in lesions of different anatomical region and size; moreover, currently employed interpretative PET positivity criteria should be adjusted to the new reconstruction method.

Polymyalgia rheumatica is the most common inflammatory rheumatic disease in elderly people, usually develops in patients older than 50 years, more frequently in females. An emerging imaging tool in the diagnostic workup of this condition is whole-body PET/CT, which allows an overall assessment of the articular and extra-articular structures involved.

Objectives To assess how patients’ dependent parameters may affect [68Ga]Ga-DOTANOC image quality and to propose a theoretical body mass index (BMI)-adjusted injected activity (IA) scheme, to improve imaging of high weight patients. Methods Among patients prospectively enrolled (June-2019 and May-2020) in an Institutional Ethical Committee-approved electronic archive, we included those affected by primary gastro-entero-pancreatic (GEP) or lung neuroendocrine tumour and referred by our Institutional clinicians (excluding even minimal radiopharmaceutical extravasation, movement artifacts, renal insufficiency). All PET/CT images were acquired following EANM guidelines and rated for visual quality (1 = non-diagnostic, 2 = poor, 3 = moderate, 4 = good). Collected data included patient’s body mass, height, BMI, age, IA (injected activity), IA per Kg (IAkg), IA per BMI (IABMI), liver SUVmean, liver SUVmax standard deviation, liver-signal-to-noise (LSNR), normalized_LSNR (LSNR_norm) and contrast-to-noise ratio (CNR) for positive scans and were compared to image rating (poor vs moderate/good). Results Overall, 77 patients were included. Rating concordance was high (agreement = 81.8%, Fleiss k score = 0.806). All patients’ dependent parameters resulted significantly different between poor-rated and moderate/good rated scans (IA: p = 0.006, IAkg: p =< 0.001, body weight: p =< 0.001, BMI: p =< 0.001, IABMI: p =< 0.001). Factors significantly associated with moderate/good rating were BMI (p =< 0.001), body weight (p =< 0.001), IABMI (p =< 0.001), IAkg (p = 0.001), IA (p = 0.003), LSNR_norm (p = 0.01). The BMI-based model presented the best predictive efficiency (81.82%). IABMI performance to differentiate moderate/good from poor rating resulted statistically significant (IA-AUC = 0.78; 95% CI: 0.68–0.89; cut-off value of 4.17MBq*m ² /kg, sensitivity = 81.1%, specificity = 66.7%). If BMI-adjusted IA (=4.17*BMI) would have been applied in this population, the median IA would have slightly inferior (−4.8%), despite a different IA in each patient. Advances in knowledge BMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yeld images of better quality (especially in high-BMI patients) mantaining practical scanning times (3 min/bed).

Background – Several techniques are available to identify, among patients with mild cognitive impairment (MCI), those at risk of conversion to Alzheimer dementia (CAD). However, simple cost-effective methods to assess the risk are not available yet. Methods – This retrospective study included 143 MCI outpatients (76.6±5.2 years, 46.8% women). Baseline variables were common neuropsychological tests (including Mini Mental State Examination-MMSE and Montreal Cognitive Assessment-MoCA), brain CT and 18F-fluorodeoxyglucose (FDG)-PET. Outcome variable was CAD after 1 year. Results – At follow-up, 31 (21.7%) patients had CAD. In multivariable analysis (OR, 95% CI), female sex (4.7, 1.6-14.0), MoCA-executive component <3 (6.3, 2.1-19.2), left medial temporal atrophy (MTA) ≥3 (5.4, 1.9-15.7) and FDG-PET suggesting CAD (5.4, 1.9-15.7) were associated with CAD (area under ROC curve 0.873). Without FDG-PET, MMSE score <28 remained associated with CAD (6.0, 2.2-16.9). As first step (before FDG-PET execution), we counted 1 point for MMSE <28, executive MoCA <3 and left MTA ≥3. With 2-3 points CAD probability was high (75%) and with 0 points it was low (6.5%). Thus, FDG-PET (second step) might be performed only in patients with 1 point (probability 19.7%, 42.7% of patients). Among them, 35% had a positive FDG-PET, suggesting high risk. Overall, 28.0% of patients were considered at high risk (specificity 83.9%, sensitivity 71.0%, accuracy 81.1%). Conclusion – With a 2-step procedure, less than half of MCI patients might undergo FDG-PET and nearly a quarter of our patients was found to be at high CAD risk, including almost three quarters of future CADs.