The Influence of Additional Treatments on the Survival of Patients Undergoing Transarterial Radioembolization (TARE).

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan-Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.

Applications of PET and SPECT in Patients with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) consists of neurological development disorders that manifest before three years of age and affect social interactions, markedly restricting range of interests and activities, often associated with some degree of intellectual disability. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive imaging tools to investigate the function of the brain in vivo. SPECT and PET studies exploring rCBF and brain glucose metabolism in patients with ASD have been performed, providing important insights into the brain regions involved in ASD. Abnormalities in serotonergic, dopaminergic, GABAergic, cholinergic, and glutamatergic systems have been suggested to contribute to the observed distorted brain circuitry associated with ASD. However, the specificity of such abnormalities needs to be fully clarified because schizophrenia and other psychiatric diseases have been shown to present with comparable changes in neurotransmitter systems. Neuroinflammation could also play a role in the development of autism. Therefore, ASD is a complicated process involving a number of factors. It is mandatory to perform more research studies to determine the molecular cornerstone of ASD and to improve our comprehension of the clinical correlates of ASD.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18 F-fluorodeoxyglucose pattern in a long-known syndrome.

AIM: Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [ 18 F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. METHODS: We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [ 18 F]FDG-PET. The 18 F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. RESULTS: Seven iNPH patients (mean age 74 ±â€…6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism ( P  = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism ( P  = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed ( P  < 0.001 corrected for multiple comparisons). CONCLUSION: In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Characterization of Mediastinal Bulky Lymphomas with FDG-PET-Based Radiomics and Machine Learning Techniques.

BACKGROUND: This study tested the diagnostic value of 18F-FDG PET/CT (FDG-PET) volumetric and texture parameters in the histological differentiation of mediastinal bulky disease due to classical Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL) and grey zone lymphoma (GZL), using machine learning techniques. METHODS: We reviewed 80 cHL, 29 PMBCL and 8 GZL adult patients with mediastinal bulky disease and histopathological diagnoses who underwent FDG-PET pre-treatment. Volumetric and radiomic parameters were measured using FDG-PET both for bulky lesions (BL) and for all lesions (AL) using LIFEx software (threshold SUV ≥ 2.5). Binary and multiclass classifications were performed with various machine learning techniques fed by a relevant subset of radiomic features. RESULTS: The analysis showed significant differences between the lymphoma groups in terms of SUVmax, SUVmean, MTV, TLG and several textural features of both first- and second-order grey level. Among machine learning classifiers, the tree-based ensembles achieved the best performance both for binary and multiclass classifications in histological differentiation. CONCLUSIONS: Our results support the value of metabolic heterogeneity as an imaging biomarker, and the use of radiomic features for early characterization of mediastinal bulky lymphoma.

FDG PET/CT Volume-Based Quantitative Data and Survival Analysis in Breast Cancer Patients: A Systematic Review of the Literature.

PURPOSE: The study aims to assess the role of SUVs, MTV, TLG, and other FDG PET metric data in predicting the prognosis of patients with newly diagnosed BC. MATERIALS AND METHODS: A systematic review was conducted by using three different databases: Pub- Med, Web of Science, and EMBASE, in the period between January 2011 and May 2021. Studies on the use of FDG PET in BC patients concerning the utility of metric PET data and survival were retrieved. The following keywords were used in diverse combinations: "breast cancer", "18F-FDG", "FDG", "PET", "PET/CT", "FDG PET", "volumetric parameters", "metabolic tumor volume", "MTV", "total lesion glycolysis", "TLG", "prognosis", "prognostic". No limits were applied. The quality of selected papers was assessed by using specific criteria. RESULTS: Totally 123 articles were retrieved, but only 14 studies were selected. In the selected papers, overall, the number of patients was 1850. Overall survival (OS) was the main outcome in three studies, while both OS and disease-free survival (DFS) were considered in the remainder of most papers. PET/CT was performed in patients with BC before surgery or neoadjuvant chemotherapy in 6 studies and in metastatic BC in 8. At multivariable analyses, diverse PET metrics, such as SUVmax, MTV, and TLG, were correlated to recurrence or OS. However, a large heterogeneity for the proposal cut-off, able to discriminate between poor and good prognosis, was found. CONCLUSION: PET metrics are helpful for the prognosis stratification in patients with locally advanced or metastatic BC. However, no specific cut-off values for these variables are now available in this setting of patients.

Esophageal Cancer with Early Onset in a Patient with Cri du Chat Syndrome.

BACKGROUND: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs. METHODS: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC). A high pain threshold was also observed. Conventional and molecular cytogenetic defined the size of the deletion, and exome analysis on the trio completed the molecular work. RESULTS: Cytogenetic analysis showed a de novo chromosomal alteration: 46,XY,ishdel(5)(p14.3)(D5S28-) and arr[GRCh37] 5p15.33p14.3(1498180_19955760)x1. A quantitative sensory test demonstrated a high heat threshold. A 18f-fluorodeoxyglucose PET/TC scan of the brain failed to detect reduction of metabolism in the somatosensory area or insular cortex. Exome analysis in the trio (patient and parents) failed to identify variants to be interpreted as a likely risk factor for EAC. CONCLUSION: We conclude that the presence of well-known risk factors (maleness, obesity, gastroesophageal reflux, and Barrett's metaplasia) in a patient with very limited capability of expressing discomfort or referring clinical symptoms have been the main risk factors for developing EAC. At present, based on the available data, there is no evidence of any increased risk of developing cancer in CdC patients.

Prospective Evaluation of Different Methods for Volumetric Analysis on [18F]FDG PET/CT in Pediatric Hodgkin Lymphoma.

Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort.

Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study.

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

Brain 18 F-Florbetapir PET/CT Findings in an Early-onset Alzheimer Disease Patient Carrying Presenilin-1 G378E Mutation.

Positron emission tomography (PET) with 18 F-Fluorodeoxyglucose ( 18 F-FDG) plays an outstanding role in the diagnostic work-up of dementia. Amyloid PET imaging is a complementary imaging technique for the early detection of Alzheimer disease (AD). ß-amyloid precursor protein ( APP ), Presenilin-1 ( PSEN1 ) and Presenilin-2 ( PSEN2 ) are the 3 main causative genes responsible for autosomal dominant early-onset Alzheimer disease (EOAD). This is the first report of 18 F-Florbetapir amyloid imaging findings in a 35-year-old male patient with EOAD carrying the G378E mutation in PSEN1 gene. Brain computed tomography (CT) and magnetic resonance imaging scans showed remarkable cerebral atrophy with dilatation of the cerebrospinal fluid spaces; furthermore, a 18 F-Florbetapir PET/CT scan demonstrated also widespread remarkable accumulation of the amyloid tracer in the cerebral cortex, with reduction of the normal contrast between white and gray matter and flattening of the external cortical margins. Furthermore, PET/CT showed intense 18 F-florbetapir uptake in the striatum and in the thalamus bilaterally. Our case supports the usefulness of amyloid PET imaging in the diagnostic work-up of EOAD.

Evaluation of Age and Sex-Related Metabolic Changes in Healthy Subjects: An Italian Brain 18F-FDG PET Study.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron-emission-tomography (PET) allows detection of cerebral metabolic alterations in neurological diseases vs. normal aging. We assess age- and sex-related brain metabolic changes in healthy subjects, exploring impact of activity normalization methods. METHODS: brain scans of Italian Association of Nuclear Medicine normative database (151 subjects, 67 Males, 84 Females, aged 20-84) were selected. Global mean, white matter, and pons activity were explored as normalization reference. We performed voxel-based and ROI analyses using SPM12 and IBM-SPSS software. RESULTS: SPM proved a negative correlation between age and brain glucose metabolism involving frontal lobes, anterior-cingulate and insular cortices bilaterally. Narrower clusters were detected in lateral parietal lobes, precuneus, temporal pole and medial areas bilaterally. Normalizing on pons activity, we found a more significant negative correlation and no positive one. ROIs analysis confirmed SPM results. Moreover, a significant age × sex interaction effect was revealed, with worse metabolic reduction in posterior-cingulate cortices in females than males, especially in post-menopausal age. CONCLUSIONS: this study demonstrated an age-related metabolic reduction in frontal lobes and in some parieto-temporal areas more evident in females. Results suggested pons as the most appropriate normalization reference. Knowledge of age- and sex-related cerebral metabolic changes is critical to correctly interpreting brain 18F-FDG PET imaging.

18F-FDG PET brain findings in disease-discordant monozygotic mosaic twins with Cri du Chat (5p-) syndrome.

We describe the first report on the genotype-phenotype patterns and [18F] fluoro-deoxygluycose (18F-FDG) Positron Emission Tomography (PET) findings in two disease-discordant monozygotic twins with Cri du Chat syndrome (CdcS) presenting deletion of 5p, 46, XY, del(5)(p14)/46, XY. One twin showed a severe phenotype; significant 18F-FDG PET hypometabolism (p=0.001) was revealed in the left and right hemispheres, thalamus, cerebellum, and midbrain, whereas hypermetabolism was detected in the left premotor cortex. The other twin presented a mild phenotype; significant hypometabolism was detected only in the right side (parahippoccampal gyrus and cerebellum). Further studies should investigate the causes of phenotypic discordance in twins with CdcS.

To Enhance or Not to Enhance? The Role of Contrast Medium 18F-FDG PET/CT in Recurrent Ovarian Carcinomas.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings; however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT; 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

AIM: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. METHODS: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. RESULTS: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. CONCLUSIONS: Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40336-021-00445-w.

The Role of PET in Supratentorial and Infratentorial Pediatric Brain Tumors.

OBJECTIVE: This review aims to provide a summary of the clinical indications and limitations of PET imaging with different radiotracers, including 18F-fluorodeoxyglucose (18F-FDG) and other radiopharmaceuticals, in pediatric neuro-oncology, discussing both supratentorial and infratentorial tumors, based on recent literature (from 2010 to present). METHODS: A literature search of the PubMed/MEDLINE database was carried out searching for articles on the use of PET in pediatric brain tumors. The search was updated until December 2020 and limited to original studies published in English after 1 January 2010. RESULTS: 18F-FDG PET continues to be successfully employed in different settings in pediatric neuro-oncology, including diagnosis, grading and delineation of the target for stereotactic biopsy, estimation of prognosis, evaluation of recurrence, treatment planning and assessment of treatment response. Nevertheless, non-18F-FDG tracers, especially amino acid analogues seem to show a better performance in each clinical setting. CONCLUSIONS: PET imaging adds important information in the diagnostic work-up of pediatric brain tumors. International or national multicentric studies are encouraged in order to collect larger amount of data.

The role of 18F-Fluorodeoxyglucose PET/CT in restaging patients with small cell lung cancer: a systematic review.

AIM: 18F-Fluorodeoxyglucose (FDG) PET imaging may play an important role in the restaging of patients with small-cell lung cancer (SCLC),, nevertheless, a systematic review of literature was still missing in this setting. The aim of this review was to summarize the evidence on literature regarding the utility of 18F-FDG PET imaging in restaging patients with SCLC. METHODS: A literature search was performed to retrieve original studies using 18F-FDG PET or 18F-FDG PET/computed tomography (CT) in a minimum of 10 patients with SCLC at restaging. RESULTS: The selected literature (17 studies) was discussed in four sections: detection rate, impact on management, prediction of prognosis and evaluation of the response to therapy. According to the literature, PET imaging may result in discordance with conventional imaging, mainly contrast-enhanced CT (ceCT), and detect additional lesions in a certain proportion of cases, leading to upstaging or downstaging. A variable level of disagreement between PET and conventional imaging has been reported also in the evaluation of response to therapy. A positive PET study is associated with shorter survival, especially in the presence of distant metastases. According to some studies, semiquantitative parameters are also inversely associated with overall survival and progression-free survival. Although the retrieved articles proved the utility of 18F-FDG PET imaging in each clinical setting, literature is still limited. CONCLUSIONS: This review encourages the use of 18F-FDG PET imaging, especially in conjunction with ceCT in recurrent SCLC patients. Further level I evidence is needed to further assess the diagnostic and prognostic capability of 18F-FDG PET/ceCT findings in SCLC.

The role of the deep convolutional neural network as an aid to interpreting brain [18F]DOPA PET/CT in the diagnosis of Parkinson's disease.

OBJECTIVES: To test the performance of a 3D convolutional neural network (CNN) in analysing brain [18F]DOPA PET/CT in order to identify patients with nigro-striatal neurodegeneration. We evaluated the robustness of the 3D CNN by testing it against a manual regional analysis of the striata by using a striatal-to-occipital ratio (SOR). METHODS: We analyzed patients who had undergone [18F]DOPA PET/CT from 2016 to 2018. Two examiners interpreted PET/CT images as positive or negative. Only patients with at least 2 years of follow-up and an ascertained neurological diagnosis were included. A 3D CNN was developed to evaluate [18F]DOPA PET/CT and refine the diagnosis of movement disorder. This system required training and testing, which were carried out on 2/3 and 1/3 of patients, respectively. A regional analysis was also conducted by drawing region of interest on T1-weighted 3D MRI scans, on which the [18F]DOPA PET images were first co-registered. RESULTS: Ninety-eight patients were enrolled: 43 presented nigro-striatal degeneration and 55 negative cases used as controls. After training on 69 patients, the diagnostic performance of the 3D CNN was then calculated in 29 patients. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 100%, 89%, 100%, 85% and 93%, respectively. When we compared the 3D CNN results with the SOR analysis, we found that the two patients falsely classified as positive by the 3D CNN procedure showed SOR values ≤ 5th percentile of the negative cases' distribution. CONCLUSIONS: 3D CNNs are able to interpret [18F]DOPA PET/CT properly, revealing patients affected by Parkinson's disease. KEY POINTS: • [18F]DOPA PET/CT is a sensitive diagnostic tool to identify patients with nigro-striatal neurodegeneration. • A semiquantitative evaluation of the images allows a more confident interpretation of the PET findings. • 3D convolutional neural network allows an accurate interpretation of 18F-DOPA PET/CT images, revealing patients affected by Parkinson's disease.

Additional value of volumetric and texture analysis on FDG PET assessment in paediatric Hodgkin lymphoma: an Italian multicentric study protocol.

INTRODUCTION: Assessment of response to therapy in paediatric patients with Hodgkin lymphoma (HL) by 18F-fluorodeoxyglucose positron emission tomography/CT has become a powerful tool for the discrimination of responders from non-responders. The addition of volumetric and texture analyses can be regarded as a valuable help for disease prognostication and biological characterisation. Based on these premises, the Hodgkin Lymphoma Study Group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) has designed a prospective evaluation of volumetric and texture analysis in the Italian cohort of patients enrolled in the EuroNet-PHL-C2. METHODS AND ANALYSIS: The primary objective is to compare volumetric assessment in patiens with HL at baseline and during the course of therapy with standard visual and semiquantitative analyses. The secondary objective is to identify the impact of volumetric and texture analysis on bulky masses. The tertiary objective is to determine the additional value of multiparametric assessment in patients having a partial response on morphological imaging.The overall cohort of the study is expected to be round 400-500 patients, with approximately half presenting with bulky masses. All PET scans of the Italian cohort will be analysed for volumetric assessment, comprising metabolic tumour volume and total lesion glycolysis at baseline and during the course of therapy. A dedicated software will delineate semiautomatically contours using different threshold methods, and the impact of each segmentation techniques will be evaluated. Bulky will be defined on contiguous lymph node masses ≥200 mL on CT/MRI. All bulky masses will be outlined and analysed by the same software to provide textural features. Morphological assessment will be based on RECIL 2017 for response definition. ETHICS AND DISSEMINATION: The current study has been ethically approved (AIFA/SC/P/27087 approved 09/03/2018; EudraCT 2012-004053-88, EM-04). The results of the different analyses performed during and after study completion the will be actively disseminated through peer-reviewed journals, conference presentations, social media, print media and internet.

Validation of FDG-PET datasets of normal controls for the extraction of SPM-based brain metabolism maps.

PURPOSE: An appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating [18F]FDG PET brain datasets of healthy controls (HC), based on publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level. METHODS: Selection of HC images was based on visual rating, after Cook's distance and jack-knife analyses, to exclude artefacts and/or outliers. The performance of these HC datasets (ADNI-HC and AIMN-HC) to extract hypometabolism patterns in single patients was tested in comparison with the standard reference HC dataset (HSR-HC) by means of Dice score analysis. We evaluated the performance and comparability of the different HC datasets in the assessment of single-subject SPM-based hypometabolism in three independent cohorts of patients, namely, ADD, bvFTD and DLB. RESULTS: Two-step Cook's distance analysis and the subsequent jack-knife analysis resulted in the selection of n = 125 subjects from the AIMN-HC dataset and n = 75 subjects from the ADNI-HC dataset. The average concordance between SPM hypometabolism t-maps in the three patient cohorts, as obtained with the new datasets and compared to the HSR-HC standard reference dataset, was 0.87 for the AIMN-HC dataset and 0.83 for the ADNI-HC dataset. Pattern expression analysis revealed high overall accuracy (> 80%) of the SPM t-map classification according to different statistical thresholds and sample sizes. CONCLUSIONS: The applied procedures ensure validity of these HC datasets for the single-subject estimation of brain metabolism using voxel-wise comparisons. These well-selected HC datasets are ready-to-use in research and clinical settings.

How to better stratify the risk of differentiated thyroid carcinomas: the key role of radioactive iodine therapy, age, and gender.

PURPOSE: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. METHODS: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (ΔC-index = + 5.1%, P < .001). CONCLUSIONS: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

Correlation of multimodal 18F-DOPA PET and conventional MRI with treatment response and survival in children with diffuse intrinsic pontine gliomas.

To evaluate the contribution of 18F-dihydroxyphenylalanine (DOPA) PET in association with conventional MRI in predicting treatment response and survival outcome of pediatric patients with diffuse intrinsic pontine gliomas (DIPGs). Methods: We retrospectively analyzed 19 children with newly diagnosed DIPGs who underwent 18F-DOPA PET/CT and conventional MRI within one week of each other at admission and subsequent MRI follow-up. Following co-registration and fusion of PET and MRI, 18F-DOPA uptake avidity and extent (PET tumor volume and uniformity) at admission, along with MRI indices including presence of ring contrast-enhancement, tumor volume at admission and at maximum response following first-line treatment, were evaluated and correlated with overall survival (OS). The association between 18F-DOPA uptake tumor volume at admission and MRI tumor volume following treatment was evaluated. Statistics included Wilcoxon signed-rank and Mann-Whitney U tests, Kaplan-Meier OS curve and Cox analysis. Results: DIPGs with a 18F-DOPA uptake Tumor/Striatum (T/S) ratio >1 presented an OS ≤ 12 months and lower degree of tumor volume reduction following treatment (p = 0.001). On multivariate analysis, T/S (p = 0.001), ring enhancement (p = 0.01) and the degree of MRI tumor volume reduction (p = 0.01) independently correlated with OS. In all patients, areas of increased 18F-DOPA uptake overlapped with regions demonstrating more prominent residual components/lack of response following treatment. Conclusions:18F-DOPA PET provides useful information for evaluating the metabolism of DIPGs. T/S ratio is an independent predictor of outcome. 18F-DOPA uptake extent delineates tumoral regions with a more aggressive biological behaviour, less sensitive to first line treatment.