What to Trust, PSA or [Ga-68]Ga-PSMA-11:Learn from Experience

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [Ga-68]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [Ga-68]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level

Exploring the Distinct Effect of Age at Onset and Caudate Denervation on Cognitive Deficits in Early Parkinson's Disease

Older age at onset and baseline caudate dopaminergic denervation are recognized risk factors for cognitive impairment in Parkinson's disease (PD), posing challenges in identifying their relative contribution to cognitive outcomes. The objective of this study was to assess the distinct contribution of age at onset and baseline caudate dopaminergic binding to the early cognitive deficits in PD patients. We examined the relationship between baseline dopaminergic striatal dysfunction (measured using [ 123 I]-FP-CIT SPECT), age at disease onset and neuropsychological performance in 128 drug-naive PD patients, utilizing putaminal and caudate binding values of 77 healthy controls (HC) for a comparative exploration of age-dependent loss of DAT availability. Additionally, we investigated whether age at onset and DAT binding value of the caudate could independently predict cognitive changes over a median of 7-year follow-up. [ 123 I]-FP-CIT-SPECT binding values had a significant negative correlation with age in both PD and HC, but in PD, aging was linked with a steeper slope for the caudate than the putamen. Older age at onset and lower caudate uptake were associated with worse global cognitive function and performance in specific neuropsychological tests at baseline and demonstrated to be significant independent predictors of cognitive dysfunction at follow-up. Our findings confirm a differential age effect on [ 123 I]-FP-CIT binding in the striatal subregions of de novo PD patients. Notably, we found less age-related attrition of dopaminergic binding in the putamen than in the caudate, reflecting likely the superimposition of putaminal compensatory mechanisms and an increased predisposition of old onset PD patients to develop cognitive disturbances

A first look into radiomics application in testicular imaging: A systematic review

The aim of this systematic review was to evaluate the state of the art of radiomics in testicular imaging by assessing the quality of radiomic workflow using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A systematic literature search was performed to find potentially relevant articles on the applications of radiomics in testicular imaging, and 6 final articles were extracted. The mean RQS was 11,33 ± 3,88 resulting in a percentage of 31,48% ± 10,78%. Regarding QUADAS-2 criteria, no relevant biases were found in the included papers in the patient selection, index test, reference standard criteria and flow-and-timing domain. In conclusion, despite the publication of promising studies, radiomic research on testicular imaging is in its very beginning and still hindered by methodological limitations, and the potential applications of radiomics for this field are still largely unexplored

Bridging brain structural/functional connectivity and tau load in progressive supranuclear palsy: A [18F]PI-2620 PET/MRI study

Introduction Progressive supranuclear palsy (PSP) is a primary 4-repeat (4R) tauopathy clinically characterized by postural instability with falls, akinesia, ocular motor dysfunction and cognitive decline. The clinical symptoms of PSP have strong overlaps with other neurodegenerative disorders and the diagnosis of definite PSP is only post mortem by establishing region-specific tau aggregates predominantly in the brainstem, basal ganglia and cerebellar nuclei. The novel second-generation tau-PET tracer [18F]PI-2620 showed a high binding affinity for aggregated 3/4R tau in Alzheimer’s disease (AD), as well as high affinity to recombinant 4R tau fibrils in non-AD tauopathies. [18F]PI-2620 imaging also proved to aid in diagnosing and differentiating patients with suspected PSP, potentially facilitating a more reliable diagnosis of PSP. Besides, there is gathering evidence supporting the concept of disrupted and reorganized structural and functional connectivities in PSP that might be influenced by tau pathology. Therefore, the present PET/MRI study with novel tau-PET tracer, we aimed to assess the structural and connectivity network properties in PSP patients and their relation to tau burden. Material and methods Ten PSP patients (age 72±7 years, 6 female) underwent 60 minutes of dynamic PET imaging following 300 MBq bolus injection of [18F]PI-2620 on an integrated 3T PET/MRI system. The binding potential (BP) was estimated using non-invasive pharmacokinetic modeling (MRTM2 in PMOD). Diffusion tensor imaging (DTI) and resting-state fMRI were acquired simultaneously and compared to the measurements of ten healthy controls (age 65±8 years, 4 female). Two networks: the whole-brain and deep gray matter (DGM) networks have ween generated. For the whole-brain network, we used default atlas-based (a combination of the Harvard-Oxford atlas and the AAL atlas) definition of 132 cortical and subcortical region of interests (ROIs), while for the DGM network, a custom atlas was generated consisting of thirteen PSP-target regions: putamen, globus pallidum externus (GPe), substantia nigra (SN), subthalamic nucleus (STN), periaqueductal gray matter, red nucleus (RN) and dentate nucleus (DN). A graph theory approach and functional network connectivity (FNC) analysis were applied to investigate PSP-related structural and effective functional connectivities, derived respectfully, from probabilistic tractography (network mode) and ROI-to-ROI functional connectivity (RRC) analysis. A possible association between tau load and various network attributes were studied. For voxel-wise analysis, between-subject effect and regression model were designed using the General Linear Model (GLM) and a false discovery rate (FDR) for multiple testing correction of pFDR < 0.05 was applied. In addition, Student's t-test and Spearman's rank correlation coefficient were used, respectively, for between-group differences of the global network attributes and their association with BP. Results For whole-brain structural connectivity, at the global network level, the number of triangles, density, and the spatial distance was lower, while assortativity degree and vulnerability were higher in PSP patients compared to controls (p0.60, p<0.05). The “hubness” scores demonstrated a negative association with BP in the left cerebellar crus (r=-0.76, p<0.05). For whole-brain functional connectivity, 17292 functional connections among 132 ROIs were analyzed. The between-subject effect depicted three clusters, showing increased connectivity between frontal-orbital cortex and cerebellar vermis and decreased connectivity between putamen and mid-temporal gyrus in PSP patients compared to controls (pFDR < 0.05). Regression analysis showed a negative relationship between BP in the bilateral DN and cerebellar-putaminal/cerebellar-pallidal connectivity (pFDR < 0.05). For deep grey network structural connectivity, at the vertex level, local efficiency was lower in SN/RN (left) and bilateral DN; average path length was decreased in STN (left) and putamen (right), while increased in ST/RN (left) and GPe (right); vertex strength was higher in the bilateral ST; nodal vulnerability was increased in STN/DN (left) and putamen (right), while decreased in all other regions. The BP showed an inverse relationship with nodal assortativity for bilateral putamen/RN/STN and with vulnerability for STN (left). For deep grey network functional connectivity, at the global network level, the global and local efficiencies, clustering coefficient, and betweenness centrality were significantly lower, while average path length and degree were higher in PSP compared to controls. At the vertex level, global efficiency was lower for putamen/ST (left) and STN/RN (right); average path length and degree were higher for putamen/ST (left). The BP showed a strong relationship (r=-0.7, p<0.05) with local efficiency and clustering coefficient for all nodes; additionally, the STN (left) showed an association with global efficiency, degree, average path length, and betweenness centrality. Conclusion Graph theory and FNC analysis of the structural and functional connectivities depicted various divergences both for whole-brain and DGM network properties, indicating lower network integration and higher segregation in PSP patients compared to controls. Aberrant frontal-cerebellar functional connectivity was presented in PSP patients that seem to be influenced by tau-pathology in the cerebellar DN. The PSP-related tau pathology appears to be associated with different measures of network structures. Cerebellum and cerebellar crus might impede the smoothness of the information passage in association with increased tau load. These results support the network degradation/reorganization concept in response to tau pathology and motivate future investigations in a larger PSP patient cohort

Brain MRI Abnormalities in Angelman Syndrome: Volumetric and Shape Analyses of Cortical and Subcortical Structures

Background: Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternally imprinted gene UBE3A. It is characterized by intellectual disability, speech impairment, peculiar behavior phenotype, seizures and movement disorder. Despite the severe neurobehavioral phenotype of AS, routine brain magnetic resonance imaging (MRI) is usually normal, although mild cortical atrophy or dysmyelination have been described. Advance quantitative MRI approaches for examining brain structure may provided important insight into potential neuroanatomical mechanisms contributing to AS. Our objective was to adopt a voxel-based morphometry (VBM) and vertex-wise shape analyses for comprehensive exploration of the cortical and subcortical grey matter (GM) structures in children with AS. Material and Methods: Molecularly conformed 18 AS children due to deletions of the maternally inherited UBE3A gene located in the chromosome 15q11.2-q13 (mean age 7.19 ± 3.46 years, seven males) and 17 healthy controls (mean age 6.85 ± 2.62 years, six males) underwent MRI examination with sedation. High resolution T1-weighted MRI images were used for optimised VBM protocol, brain segmentation and vertex-wise shape analysis of the subcortical structures. Between groups comparison was done by independent sample t test or non-parametric Mann-Whitney U-tests. The analysis after adjusting for covariates (intracranial volume, age and sex) was carried out by general linear model (GLM) with categorical variables as fixed effect and continuous variables as covariates. Statistical dependance between volume of the structures and age was assessed by Sperman’s rank correlation. For voxel-wise VBM analysis, threshold-free cluster enhancement option was applied with 5000 permutations with age as a nuisance covariate. For vertex-wise shape analysis cluster-based option was used with 5000 permutations, as recommended. The level of p < 0.05, controlled for family-wise error rate, was was considered as significant for all voxel-wise statistics. Results: The whole-brain VBM analysis demonstrates GM loss in AS children compared to controls in the cerebellar hemispheres and vermis, the right and left striatum, the frontal cortex bilaterally and the limbic structures (hippocampi, amygdalae, parahippocampal and cingulate cortices). The cortical grey/white matter and subcortical structures’ volumes were significantly lower for AS children compared to controls even after regressing out the effects of age, intracranial volume and gender. Vertex-wise shape analysis of subcortical structures showed local displacement with inward deflection of vertices in the caudate nuclei and amygdalae bilaterally, while deformations were noted on the right hemisphere in the head of the hippocampus, putamen and ventromedial surface of the palladium. Conclusions: Our results demonstrated, for the first time, regional specific GM loss in the cortical and subcortical structures in children with AS that might reflect brain regions with the loss and/or marked reduction of maternal-specific expression of UBE3A. Applying in vivo advance MRI, we conformed the results of animal studies demonstrating that AS children have lower total cortical volume, as well as remarkable GM volume loss of all subcortical structures. The lateralized shape deformation patterns with inward deflection of vertices were found for subcortical structures more prominent on the right hemisphere that may possibly indicate the differential maternal expression levels of the UBE3A in the left and right subcortical structures

Explainable AI in radiology: a white paper of the Italian Society of Medical and Interventional Radiology

The term Explainable Artificial Intelligence (xAI) groups together the scientific body of knowledge developed while searching for methods to explain the inner logic behind the AI algorithm and the model inference based on knowledge-based interpretability. The xAI is now generally recognized as a core area of AI. A variety of xAI methods currently are available to researchers; nonetheless, the comprehensive classification of the xAI methods is still lacking. In addition, there is no consensus among the researchers with regards to what an explanation exactly is and which are salient properties that must be considered to make it understandable for every end-user. The SIRM introduces an xAI-white paper, which is intended to aid Radiologists, medical practitioners, and scientists in the understanding an emerging field of xAI, the black-box problem behind the success of the AI, the xAI methods to unveil the black-box into a glass-box, the role, and responsibilities of the Radiologists for appropriate use of the AI-technology. Due to the rapidly changing and evolution of AI, a definitive conclusion or solution is far away from being defined. However, one of our greatest responsibilities is to keep up with the change in a critical manner. In fact, ignoring and discrediting the advent of AI a priori will not curb its use but could result in its application without awareness. Therefore, learning and increasing our knowledge about this very important technological change will allow us to put AI at our service and at the service of the patients in a conscious way, pushing this paradigm shift as far as it will benefit us

Advancing Pediatric Sarcomas through Radiomics: A Systematic Review and Prospective Assessment Using Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS)

: Pediatric sarcomas, rare malignancies of mesenchymal origin, pose diagnostic and therapeutic challenges. In this review, we explore the role of radiomics in reshaping our understanding of pediatric sarcomas, emphasizing methodological considerations and applications such as diagnostics and predictive modeling. A systematic review conducted up to November 2023 identified 72 papers on radiomics analysis in pediatric sarcoma from PubMed/MEDLINE, Web of Knowledge, and Scopus. Following inclusion and exclusion criteria, 10 reports were included in this review. The studies, predominantly retrospective, focus on Ewing sarcoma and osteosarcoma, utilizing diverse imaging modalities, including CT, MRI, PET/CT, and PET/MRI. Manual segmentation is common, with a median of 35 features extracted. Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS) assessments reveal a consistent emphasis on non-radiomic features, validation criteria, and improved methodological rigor in recent publications. Diagnostic applications dominate, with innovative studies exploring prognostic and treatment response aspects. Challenges include feature heterogeneity and sample size variations. The evolving landscape underscores the need for standardized methodologies. Despite challenges, the diagnostic and predictive potential of radiomics in pediatric oncology is evident, paving the way for precision medicine advancements

3D-Flair sequence at 3T in cochlear otosclerosis

Purpose: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. Materials and methods: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). Results: We revealed no endocochlear signal abnormalities on T1-weighted –/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. Conclusion: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. Key Points: • Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage.• 3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction.• Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown.• Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities.• 3D-FLAIR might be applied for monitoring disease progression and treatment response