Previous findings suggest that the altered punishment sensitivity displayed by individuals with Alcohol Use Disorder (AUD) might reflect lower levels of loss aversion (LA), i.e., the tendency to overweigh negative relative to positive choice consequences. However, whether lower LA represents a core facet of abnormal decision-making in AUD, rather than a secondary consequence of defective executive functioning, remains debated. We used a gambling task to compare LA across 22 AUD patients and 19 age-, sex-, and education-matched healthy controls, and 18F-FDG-PET to investigate its neural correlates in the AUD sample, using 42 age/sex-matched PET healthy controls as the reference group for analyses on brain metabolism. Although AUD patients displayed both significantly lower LA and a hypometabolic pattern in the anterior cingulate and anterior insular nodes of the salience network, the behavioral finding was not explained by altered attentional or executive skills. Instead, we observed a negative relationship with left anterior insular metabolism and LA, possibly reflecting altered regulation of emotions associated with interoceptive processing. Within the AUD sample, lower LA was associated with a steeper negative relationship with frontomedial metabolism in males than in females, suggesting sex-related modulation of its neural correlates. While providing novel insights into the hypometabolic brain pattern associated with lower LA in AUD, these findings unveil sex-specific effects calling for tailored intervention approaches both in research and clinical practice.

Planar cardiac scintigraphy with [123I]I-mIBG is widely used to image myocardial sympathetic activity. In multicentre studies, different γ-cameras can cause variability in quantitative parameters. This study aimed to harmonise multicentre [123I]I-mIBG data using a custom-designed phantom and to assess its feasibility and acceptability. A ‘tube and bottle’ phantom was designed to standardise the heart-to-mediastinum (H/M) ratio across 15 centres. Each centre prepared three versions of the phantom (A, B, and C) with varying pertechnetate ([99mTc]Tc-O4-) activities, acquired static images using their own γ-camera, and uploaded DICOM data to a shared platform. In the phantom, the tube and bottle represent the heart and mediastinum, respectively, with the tube-to-bottle (T/B) ratio simulating the H/M ratio. The reference centre analysed the images and calculated the T/B ratios, applying linear regression for data harmonisation. A survey was conducted to assess the phantom’s usability. The harmonised T/B ratios for versions A and B were 20.46 ± 0.78 and 6.19 ± 0.39, respectively. The average slope and intercept of the regression line across the participating centres resulted in 1.07 ± 0.38 and − 0.82 ± 4.95. Survey feedback indicated high feasibility and acceptability, with all centres recommending the phantom for multicentre harmonisation. The custom-made phantom effectively harmonised experimental data across different centres, supporting its use in multicentre studies to improve data consistency.

BackgroundMeasuring 18F-FDG PET-detected brain glucose uptake provides reliable information on metabolic tissue abnormalities, cells dysfunction, and neurovascular changes after traumatic brain injury (TBI).ObjectivesWe aimed to study the relationship between post-traumatic brain glucose metabolism and functional outcomes in the so far unexplored field of longitudinally 18F-FDG PET-monitored patients undergoing rehabilitation after moderate-to-severe TBI.MethodsFourteen patients consecutively admitted to our unit in the post-acute phase after TBI underwent 18F-FDG-PET scans performed before and 6 months after inpatient rehabilitation program. The Glasgow Coma Scale (GCS) for neurological status, and the Functional Independence Measure (FIM) plus the Glasgow Outcome Scale-Extended (GOSE) scales for the rehabilitation outcome, were applied on admission and discharge. Voxel-wise analyses were performed, with the Statistical Parametric Mapping (SPM12) software, to investigate pre- vs. post-rehabilitation changes of brain metabolism, and their relationships with clinical indices.ResultsIn the whole sample, 18F-FDG uptake significantly increased in the following five regions that were hypometabolic before rehabilitation: inferior frontal gyrus bilaterally, alongside right precentral gyrus, inferior parietal lobule, and cerebellum. However, only for the right precentral gyrus the median voxel peak-value at baseline resulted a significant predictor of both cognitive (FIM cognitive subscale, p = 0.012), and functional (GOS-E, p = 0.02; post- vs. pre-treatment GOS-E difference, p = 0.009) improvements. ROC curve analysis showed that a peak voxel-value of 1.7998 was the optimal cut-off for favorable rehabilitation outcome. Unfavorable functional outcomes were predicted by increased 18F-FDG uptake in the inferior frontal gyrus (GOS-E, p = 0.032) and precentral gyrus (FIM cognitive subscale, p = 0.017; GOS-E, p = 0.015).ConclusionThis proof-of-principle study enlightens the metabolic changes occurring in moderate-to-severe TBI course. Notably, such changes preferentially involve definite frontal brain areas regardless of TBI localization and entity. These findings pave the way for further studies with translational purposes.

Neuroimaging studies have shown that cognitive impairments in Alcohol Use Disorder (AUD), particularly involving executive functions, reflect widespread structural and functional brain alterations. However, these findings mostly result from magnetic resonance imaging (MRI). To complement previous MRI findings with a more direct measure of brain metabolism, we therefore explored the neural bases of executive impairments in AUD using FDG-PET. Twenty-three AUD patients and 18 healthy controls underwent a neurocognitive assessment, and patients also an 18F-FDG-PET scan. Using as reference for brain metabolism a FDG-PET dataset of age-matched healthy controls, we assessed a relationship between executive impairment and regional hypometabolism in AUD patients, while also considering a possible moderating age effect. Compared with controls, AUD patients exhibited widespread hypometabolism in the anterior/midcingulate cortex, fronto-insular cortex, and medial precuneus, supporting the hypothesis that their impaired executive performance might reflect an altered transition from automatic to controlled processing. Patients’ worse executive performance reflected in higher metabolism in the midcingulate cortex and medial precuneus, suggesting a possible compensatory neural mechanism. This relationship was moderated by age in the right anterior insula, where the decrease of metabolism is steeper, in older patients, at the lowest level of cognitive performance. This finding suggests that an age-related decrease in the compensatory capacity of the insular node of the salience network might contribute to cognitive decline in older patients. While supporting the use of FDG-PET to improve the understanding of AUD-related cognitive decline, and differential diagnosis in older patients, these findings might help design personalized innovative treatment protocols.

ObjectivesWe aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test.MethodsAdult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results.ResultsAmong the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 +/- 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result.ConclusionsThe SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result. Patients with functional chronic diarrhea and suspicion of bile-acid diarrhea (BAD) were investigated with the 75-selenium homocholic acid taurine (SeHCAT) test. They were started on cholestyramine and the clinical response was evaluated. Predisposing factors for BAD, response to cholestyramine, and the necessity of using cholestyramine to maintain symptom control in the long-term were more common in patients with positive (pos) SeHCAT test. The SeHCAT test identifies patients who benefit from cholestyramine. Nevertheless, this drug may also be effective for patients with negative (neg) SeHCAT test result. image

PURPOSE:Radiomics has emerged as an advanced image processing methodology to define quantitative imaging biomarkers for prognosis and prediction of treatment response and outcome. The development of quantitative imaging biomarkers requires careful analysis to define their accuracy, stability and reproducibility through phantom measurements. Few efforts were devoted to develop realistic anthropomorphic phantoms. In this work, we developed a multimodality image phantom suitable for PET, CT and multiparametric MRI imaging.METHODS:A tissue-equivalent gel-based mixture was designed and tested for compatibility with different imaging modalities. Calibration measurements allowed to assess gel composition to simulate PET, CT and MRI contrasts of oncological lesions. The characterized gel mixture was used to create realistic synthetic lesions (e.g. lesions with irregular shape and non-uniform image contrast), to be inserted in a standard anthropomorphic phantom. In order to show phantom usefulness, issues related to accuracy, stability and reproducibility of radiomic biomarkers were addressed as proofs-of-concept.RESULTS:The procedure for gel preparation was straightforward and the characterized gel mixture allowed to mime simultaneously oncological lesion contrast in CT, PET and MRI imaging. Proofs-of-concept studies suggested that phantom measurements can be customized for specific clinical situations and radiomic protocols.CONCLUSIONS:We developed a strategy to manufacture an anthropomorphic, tissue-equivalent, multimodal phantom to be customized on specific radiomics protocols, for addressing specific methodological issues both in mono and multicentric studies.

To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. The TDr method requires two static scans per subject: one early (~ 0–10 min after the injection) and one late (typically 50–70 min or 90–100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical–cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

Aim. To evaluate reproducibility and stability of radiomic features as effects of the use of different volume segmentation methods and reconstruction settings. The potential of radiomics in really capturing the presence of heterogeneous tumor uptake and irregular shape was also investigated. Materials and Methods. An anthropomorphic phantom miming real clinical situations including synthetic lesions with irregular shape and nonuniform radiotracer uptake was used. 18F-FDG PET/CT measurements of the phantom were performed including 38 lesions of different shape, size, lesion-to-background ratio, and radiotracer uptake distribution. Different reconstruction parameters and segmentation methods were considered. COVs were calculated to quantify feature variations over the different reconstruction settings. Friedman test was applied to the values of the radiomic features obtained for the considered segmentation approaches. Two sets of test-retest measurement were acquired and the pairwise intraclass correlation coefficient was calculated. Fifty-eight morphological and statistical features were extracted from the segmented lesion volumes. A Mann–Whitney test was used to evaluate significant differences among each feature when calculated from heterogeneous versus homogeneous uptake. The significance of each radiomic feature in terms of capturing heterogeneity was evaluated also by testing correlation with gold standard indexes of heterogeneity and sphericity. Results. The choice of the segmentation method has a strong impact on the stability of radiomic features (less than 20% can be considered stable features). Reconstruction affects the estimate of radiomic features (only 26% are stable). Thirty-one radiomic features (53%) resulted to be reproducible, 11 of them are able to discriminate heterogeneity. Among these, we found a subset of 3 radiomic features strongly correlated with GS heterogeneity index that can be suggested as good features for retrospective evaluations.

also on a scale of 1-10, is assigned to each FM based on the nature of the failure, number of patients involved in the same error and author's experience.The Risk Priority Number or RPN is calculated as RPNZOxSxD.Process mapping is performed to illustrate different steps in HDR procedures.Faulty tree analysis (FTA) is carried out to reveal possible causes to the failures.Results: Thirty-three (33) major failure modes (FM) are identified in the study.The RPN values range from 47 to 856.The 10 riskiest FMs are: 1.New catheter or transfer tube used for treatment but lengths of old catheters are used for planning; 2. Wrong step size entered for treatment delivery (for manual afterloaders); 3. Treatment length entered wrongly in planning; 4. Incorrect measurement of catheter length; 5. Use of standard or default length instead of measured lengths in planning; 6. Catheter or applicator moves during treatment 7. Catheter/applicator insertion too close or too far; 8. Wrong set of transfer tube or catheter used for treatment; 9. Applicator insertion to the wrong site; and 10.Catheter pulled out by patients during treatment.The majority of high risk failures occur in treatment planning or treatment delivery.Faulty tree analysis (FTA) shows that organizational factors could also pose significant risks to safety.Conclusion: Reported medical events can be used to estimate RPN values for errors in HDR brachytherapy.AAPM TG 100 provides an effective tool for developing a QM program by prioritizing the use of QA resources with priorities given to the most hazardous failures or conditions.Nevertheless, the effectiveness of any QM program will ultimately be determined by individuals' quality as well as operation and safety environment.

This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.

The aim of this work was to develop a method to manufacture oncological phantoms for quantitation purposes in 18F-FDG PET and DW-MRI studies. Radioactive and diffusion materials were prepared using a mixture of agarose and sucrose radioactive gels. T2 relaxation and diffusion properties of gels at different sucrose concentrations were evaluated. Realistic oncological lesions were created using 3D-printed plastic molds filled with the gel mixture. Once solidified, gels were extracted from molds and immersed in a low-radioactivity gel simulating normal background tissue. A breast cancer phantom was manufactured using the proposed method as an exploratory feasibility study, including several realistic oncological configurations in terms of both radioactivity and diffusion. The phantom was acquired in PET with 18F-FDG, immediately after solidification, and in DW-MRI the following day. Functional volumes characterizing the simulated BC lesions were segmented from PET and DW-MRI images. Measured radioactive uptake and ADC values were compared with gold standards. Phantom preparation was straightforward, and the time schedule was compatible with both PET and MRI measurements. Lesions appeared on 18F-FDG PET and DW-MRI images as expected, without visible artifacts. Lesion functional parameters revealed the phantom’s potential for validating quantification methods, in particular for new generation hybrid PET-MRI systems.

The patient underwent an 18F-FDG PET-CT scan which showed a decrease in glucidic metabolism in parietal and occipital lobes, more prominent on the left side (white arrow). The hypometabolism was confirmed also by SPM analysis (green arrow).