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We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression. [ABSTRACT FROM AUTHOR]

Background: Analysis of [18F]-Fluorodeoxyglucose (FDG) kinetics in cancer has been most often limited to the evaluation of the average uptake over relatively large volumes. Nevertheless, tumor lesions also contain inflammatory infiltrates whose cells are characterized by a significant radioactivity washout due to the hydrolysis of FDG-6P catalyzed by glucose-6P phosphatase. The present study aimed to verify whether voxel-wise compartmental analysis of dynamic imaging can identify tumor regions characterized by tracer washout. The study included 11 patients with lung cancer submitted to PET/CT imaging for staging purposes. Tumour was defined by drawing a volume of interest loosely surrounding the lesion and considering all inside voxels with a standardized uptake value (SUV) > 40% of the maximum. Eight whole-body scans were repeated after 20 min of dynamic imaging centered on the heart. Six parametric maps were generated progressively by computing a Patlak regression line for each voxel. Each analysis considered a different set of frames: starting with all eight frames, then the last seven frames, and so on, down to the last three frames. Results: Delaying the starting point of the compartmental analysis revealed a progressive increase in the prevalence of voxels with a negative slope. In the most delayed parametric map, these voxels represented 0.5–4.5% (median 2%) of the tumor volume. This effect was independent of tumor size and was predominantly located at the lesion borders. Conclusions: The voxel-wise parametric maps provided by compartmental analysis identify a measurable volume characterized by radioactivity washout. The spatial localization of this pattern is compatible with the recognized preferential site of inflammatory infiltrates populating the tumor stroma and might improve the power of FDG imaging in monitoring the effectiveness of treatments aimed at empowering the host immune response against cancer. Trial registration: ClinicalTrials. The study was approved by the local ethical committee and it represented a single Institution ancillary trial within the expanded-access program for Nivolumab. NCT02475382. Registered 2015-06-16. URL: https://clinicaltrials.gov/study/NCT02475382?id=NCT02475382.&rank=1 [ABSTRACT FROM AUTHOR]

Late-onset primary psychiatric disease (PPD) and behavioral frontotemporal dementia (bvFTD) present with a similar frontal lobe syndrome. We compare brain glucose metabolism in bvFTD and late-onset PPD and investigate the metabolic correlates of cognitive and behavioral disturbances through FDG-PET/MRI. We studied 37 bvFTD and 20 late-onset PPD with a mean clinical follow-up of three years. At baseline evaluation, metabolism of the dorsolateral, ventrolateral, orbitofrontal regions and caudate could classify the patients with a diagnostic accuracy of 91% (95% CI: 0.81–0.98%). 45% of PPD showed low-grade hypometabolism in the anterior cingulate and/or parietal regions. Frontal lobe metabolism was normal in 32% of genetic bvFTD and bvFTD with motor neuron signs. Hypometabolism of the frontal and caudate regions could help in distinguishing bvFTD from PPD, except in cases with motor neuron signs and/or genetic bvFTD for which brain metabolism may be less informative. • Frontal lobe syndrome is shared by late-onset primary psychiatric disease and bvFTD. • Brain glucose metabolism may be mostly useful in the differential diagnosis. • Frontal cortex/caudate metabolism guided a correct classification in 91% of cases. • Sparing of frontal metabolism may be present in bvFTD with MND or genetic bvFTD. • Hypometabolism of parietal cortex may be present in psychiatric diseases. [ABSTRACT FROM AUTHOR]

Background: Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa. Methods: mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression. Results: ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization). Conclusions: The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding. [ABSTRACT FROM AUTHOR]

Objective: To identify patients with atypical ductal hyperplasia (ADH) at low risk of upgrading to carcinoma. This study aims to assess the performance of radiomics combined with clinical factors to predict occult breast cancer among women diagnosed with ADH., Methods: This study retrospectively included microcalcification clusters of patients who underwent Mx and VABB with a diagnosis of ADH at a tertiary center from January 2015 to May 2023. Clinical and radiological data (age, cluster size, BI-RADS classification, mammographic density, breast cancer history, residual microcalcifications) were collected. Surgical outcomes were used to determine upgrade. Four logistic regression models were developed to predict the risk of upgrade. The performance was evaluated using the area under the receiver operating characteristic curve (AUC) and performance scores., Results: A total of 143 patients with 153 clusters were included. Twelve radiomic features and six clinical factors were selected for model development. The sample was split into 107 training and 46 test cases. Clinical features achieved an AUC of 0.72 (0.60-0.84), radiomic features an AUC of 0.73 (0.61-0.85). Radiomic features with "cluster size" and "age" improved the AUC to 0.79 (0.67-0.91). The best model, incorporating all data, achieved an AUC of 0.82 (0.71-0.92), a specificity of 0.89 (0.75, 0.97), and NPV of 0.92 (0.78-0.98)., Conclusion: This study demonstrates the potential of radiomic as a valuable tool for reducing unnecessary treatments for patient classified as "low risk of ADH upgrade". Combining radiomic information with clinical data improved the accuracy of risk prediction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs., Methods: We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups., Results: Long-run high grey level emphasis (LRHGLE&#95;GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment., Conclusions: Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC., (© 2024. The Author(s).)

The analysis of the psoas muscle in morphological and functional imaging has proved to be an accurate approach to assess sarcopenia, i.e. a systemic loss of skeletal muscle mass and function that may be correlated to multifactorial etiological aspects. The inclusion of sarcopenia assessment into a radiological workflow would need the implementation of computational pipelines for image processing that guarantee segmentation reliability and a significant degree of automation. The present study utilizes three-dimensional numerical schemes for psoas segmentation in low-dose X-ray computed tomography images. Specifically, here we focused on the level set methodology and compared the performances of two standard approaches, a classical evolution model and a three-dimension geodesic model, with the performances of an original first-order modification of this latter one. The results of this analysis show that these gradient-based schemes guarantee reliability with respect to manual segmentation and that the first-order scheme requires a computational burden that is significantly smaller than the one needed by the second-order approach., (© 2024. The Author(s).)

Introduction: In the past few years, the use of artificial intelligence in healthcare has grown exponentially. Prescription of antibiotics is not exempt from its rapid diffusion, and various machine learning (ML) techniques, from logistic regression to deep neural networks and large language models, have been explored in the literature to support decisions regarding antibiotic prescription., Areas Covered: In this narrative review, we discuss promises and challenges of the application of ML-based clinical decision support systems (ML-CDSSs) for antibiotic prescription. A search was conducted in PubMed up to April 2024., Expert Opinion: Prescribing antibiotics is a complex process involving various dynamic phases. In each of these phases, the support of ML-CDSSs has shown the potential, and also the actual ability in some studies, to favorably impacting relevant clinical outcomes. Nonetheless, before widely exploiting this massive potential, there are still crucial challenges ahead that are being intensively investigated, pertaining to the transparency of training data, the definition of the sufficient degree of prediction explanations when predictions are obtained through black box models, and the legal and ethical framework for decision responsibility whenever an antibiotic prescription is supported by ML-CDSSs.

Objectives: In patients with locally advanced rectal carcinoma (LARC), negative nodal status after neoadjuvant chemoradiotherapy (nCRT) may allow for rectum-sparing protocols rather than total mesorectal excision; however, current MRI criteria for nodal staging have suboptimal accuracy. The aim of this study was to compare the diagnostic accuracy of different MRI dimensional criteria for nodal staging after nCRT in patients with LARC., Materials and Methods: Patients who underwent MRI after nCRT for LARC followed by surgery were retrospectively included and divided into a training and a validation cohort of 100 and 39 patients, respectively. Short-, long-, and cranial-caudal axes and volume of the largest mesorectal node and nodal status based on European Society of Gastrointestinal Radiology consensus guidelines (i.e., ESGAR method) were assessed by two radiologists independently. Inter-reader agreement was assessed in the training cohort. Histopathology was the reference standard. ROC curves and the best cut-off were calculated, and accuracies compared with the McNemar test., Results: The study population included 139 patients (median age 62 years [IQR 55-72], 94 men). Inter-reader agreement was high for long axis (κ = 0.81), volume (κ = 0.85), and ESGAR method (κ = 0.88) and low for short axis (κ = 0.11). Accuracy was similar (p > 0.05) for long axis, volume, and ESGAR method both in the training (71%, 74%, and 65%, respectively) and in the validation (83%, 78%, and 75%, respectively) cohorts., Conclusion: Accuracy of the measurement of long axis and volume of the largest lymph node is not inferior to the ESGAR method for nodal staging after nCRT in LARC., Clinical Relevance Statement: In MRI restaging of rectal cancer, measurement of the long axis or volume of largest mesorectal lymph node after preoperative chemoradiotherapy is a faster and reliable alternative to ESGAR criteria for nodal staging., Key Points: • Current MRI criteria for nodal staging in locally advanced rectal cancer after chemo-radiotherapy have suboptimal accuracy and are time-consuming. • Measurement of long axis or volume of the largest mesorectal lymph node on MRI showed good accuracy for assessment of loco-regional nodal status in locally advanced rectal cancer. • MRI measurement of the long axis and volume of largest mesorectal lymph node after chemo-radiotherapy could be a faster and reliable alternative to ESGAR criteria for nodal staging., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

A few 18 F-FDG PET/CT studies have revealed the presence of brain hypermetabolism in the brain stem and cervical spinal cord of patients within the amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) continuum. We aimed to investigate this finding through a hybrid PET/MRI system, allowing a more precise depiction of the spatial pattern of metabolic changes in the brain stem and cervical spinal cord. Methods: Twenty-eight patients with a diagnosis of ALS or a diagnosis of the behavioral variant of FTD plus motoneuron disease, as well as 13 control subjects, underwent 18 F-FDG PET/MRI. Mean normalized 18 F-FDG uptake in the midbrain/pons, medulla oblongata, and cervical spinal cord as defined on the individual's MRI scans were compared between groups. Furthermore, the associations between regional 18 F-FDG uptake and clinical and demographic characteristics-including gene mutation, type of onset (bulbar, spinal, dementia), and clinical characteristics-were investigated. Results: A significant ( P < 0.005) increment in glucose metabolism in the midbrain/pons and medulla oblongata was found in ALS/FTD patients (spinal-ALS and FTD-motor neuron disease subgroups) in comparison to controls. No relevant associations between clinical and metabolic features were reported, although medulla oblongata hypermetabolism was associated with shortened survival ( P < 0.001). Conclusion: Increased glucose metabolism in the brain stem might be due to neuroinflammation, one of the key steps in the pathogenic cascade that leads to neurodegeneration in ALS/FTD. 18 F-FDG PET/MRI could be a valuable tool to assess glial changes in the ALS/FTD spectrum and could serve as a prognostic biomarker. Large prospective initiatives would likely shed more light on the promising application of PET/MRI in this setting., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-769). The authors have no conflicts of interest to declare.

Objective: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2- 18 F-fluoroethyl)-L-tyrosine positron emission tomography ([ 18 F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [ 18 F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib., Methods: We retrospectively reviewed 16 consecutive GBM patients who underwent [ 18 F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [ 18 F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis., Results: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC ( R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects ( p = 0.0023). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria ( p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival., Conclusion: In recurrent glioblastoma patients treated with regorafenib, [ 18 F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment., Advances in Knowledge: Simultaneous evaluation of [ 18 F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.

Objective: The objective of the study was to assess the advantages of 18 F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography with magnetic resonance (PET/CT-MR) in diagnosing and monitoring patients with adult-onset Still's disease (AOSD). Methods: Participants in this retrospective case-control study underwent whole-body 18 F-FDG-PET/CT-MR imaging. All PET scans were qualitatively and semiquantitatively analyzed using standardized uptake values (SUVs) normalized to liver uptake, i.e., we calculated the ratio (SUVr) between the minimum, maximum, and mean SUVs for different organs and tissues and the mean SUV for the liver. Disease activity scores were assessed using Pouchot's criteria. Results: Eighteen patients diagnosed with AOSD and 24 controls (non-AOSD patients diagnosed with solid tumors, excluding lymphomas) were considered. A total of 38 PET/MR and nine PET/CT scans were analyzed. AOSD patients had higher SUVr than controls. All SUVr differed significantly between the patient and control group for bone marrow, and for the spleen, the only difference lacking statistical significance concerned the ratio of the minimum SUV for spleen to the mean SUV for liver. Though limited in number, AOSD responders to therapy showed lower uptakes during the period monitored. No correlations were found between Pouchot's scores and SUVr. Conclusion: Our data revealed higher spleen and bone marrow 18 F-FDG uptakes on PET/CT and PET/MR images in AOSD patients than in controls. Together with clinical examinations and laboratory data, PET/CT and PET/MR seemed more reliable than Pouchot's score in assessing disease activity., (Copyright © 2020 Bindoli, Galozzi, Magnani, Rubin, Campi, Doria, Cecchin and Sfriso.)

Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4 + T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18 F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18 F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18 F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18 F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18 F-FDG-PET/CT scans revealed enhanced 18 F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18 F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18 F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18 F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Increasing evidence links atherosclerosis to a decreased bone thickness. This correlation could reflect a bone/plaque interaction. Hereby we analyzed Hounsfield density (HU) and mineral turnover in bone and in the arterial calcifications (AC), using a computational method applied to PET/CT data. 79 18 F-NaF PET/CT from patients with AC were retrospectively analyzed. Mean AC density and background-corrected uptake (TBR) were estimated after semi-automatic isocontour segmentation. The same values were assessed in the trabecular bone, using an automatic adaptive thresholding method. Patients were then stratified into terciles, according to their mean HU plaque density ("light", "medium" or "heavy" calcifications"). 35 18 F-NaF PET/CT from patients without AC served as controls. Vertebral density and TBR were lower in patients than in controls (137±25 vs. 160±14 HU, P<0.001); (6.2±3.9 vs. 8.4±3.4, P<0.05). Mean trabecular TBR values were 8.3±4, 4.5±2.1 and 3.5±1.8 in light, medium and heavy AC groups, respectively (P<0.05 for light vs. medium and P<0.01 for light vs. heavy). Similarly, mean trabecular HU was 143±19, 127±26 and 119±18 in the three groups, respectively (P<0.01 for light vs. heavy). Mean AC density was inversely associated with the trabecular HU (R=-0.56, P<0.01). Conversely, plaques' TBR directly correlated with the one in trabecular bone (R=0.63, P<0.001). At multivariate analysis, the sole predictor of vertebral density was plaque HU (P<0.05). Our data highlight a correlation between plaque and bone morpho-functional parameters and suggest that observing skeletal bone characteristics could represent a novel window on atherosclerosis pathophysiology., Competing Interests: None.