Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

BACKGROUND: The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet. METHODS: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. RESULTS: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS. CONCLUSION: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

The Impact of Lateral Ventricular Opening in the Resection of Newly Diagnosed High-Grade Gliomas: A Single Center Experience.

Given the importance of maximizing resection for prognosis in patients with HGG and the potential risks associated with ventricle opening, this study aimed to assess the actual increase in post-surgical complications related to lateral ventricle opening and its influence on OS and PFS. A retrospective study was conducted on newly diagnosed HGG, dividing the patients into two groups according to whether the lateral ventricle was opened (69 patients) or not opened (311 patients). PFS, OS, subependymal dissemination, distant parenchymal recurrences, the development of hydrocephalus and CSF leak were considered outcome measures. A cohort of 380 patients (154 females (40.5%) and 226 males (59.5%)) was involved in the study (median age 61 years). The PFS averaged 10.9 months (±13.3 SD), and OS averaged 16.6 months (± 16.3 SD). Among complications, subependymal dissemination was registered in 15 cases (3.9%), multifocal and multicentric progression in 56 cases (14.7%), leptomeningeal dissemination in 12 (3.2%) and hydrocephalus in 8 (2.1%). These occurrences could not be clearly justified by ventricular opening. The act of opening the lateral ventricles itself does not carry an elevated risk of dissemination, hydrocephalus or cerebrospinal fluid (CSF) leak. Therefore, if necessary, it should be pursued to achieve radical removal of the disease.

Imaging of the Liver and Pancreas: The Added Value of MRI.

MR is a powerful diagnostic tool in the diagnosis and management of most hepatic and pancreatic diseases. Thanks to its multiple sequences, the use of dedicated contrast media and special techniques, it allows a multiparametric approach able to provide both morphological and functional information for many pathological conditions. The knowledge of correct technique is fundamental in order to obtain a correct diagnosis. In this paper, different MR sequences will be illustrated in the evaluation of liver and pancreatic diseases, especially those sequences which provide information not otherwise obtainable with other imaging techniques. Practical MR protocols with the most common indications of MR in the study of the liver and pancreas are provided.

Biochemical characterization on muscle tissue of a novel biallelic ACO2 mutation in an infant with progressive encephalopathy.

The ACO2 gene encodes the mitochondrial protein aconitate hydratase, which is responsible for catalyzing the interconversion of citrate into isocitrate in the tricarboxylic acid (TCA) cycle. Mitochondrial aconitase is expressed ubiquitously, and deficiencies in TCA-cycle enzymes have been reported to cause various neurodegenerative diseases due to disruption of cellular energy metabolism and development of oxidative stress. We investigated a severe early infantile-onset neurometabolic syndrome due to a homozygous novel variant in exon 13 of the ACO2 gene. The in vitro pathogenicity of this variant of unknown significance was demonstrated by the loss of both protein expression and its enzymatic activity on muscle tissue sample taken from the patient. The patient presented with progressive encephalopathy soon after birth, characterized by hypotonia, progressive severe muscle atrophy, and respiratory failure. Serial brain magnetic resonance imaging showed progressive abnormalities compatible with a metabolic disorder, possibly mitochondrial. Muscle biopsy disclosed moderate myopathic alterations and features consistent with a mitochondriopathy albeit nonspecific. The course was characterized by progressive worsening of the clinical and neurological picture, and the patient died at 5 months of age. This study provides the first report on the validation in muscle from human subjects regarding in vitro analysis for mitochondrial aconitase activity. To our knowledge, no prior reports have demonstrated a correlation of phenotypic and diagnostic characteristics with in vitro muscle enzymatic activity of mitochondrial aconitase in humans. In conclusion, this case further expands the genetic spectrum of ACO2 variants and defines a complex case of severe neonatal neurometabolic disorder.

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT: disease extent analysis and correlations with pulmonary function tests.

BACKGROUND: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). MATERIAL AND METHODS: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value < 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD>30% or 10%20% or 20% with FVC%<70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value<0.025) were computed between ILD extents and PFT (FVC% and DLCO%). RESULTS: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were -0.66, -0.60 and -0.68 with FVC, -0.59, -0.56 and -0.57 with DLCO, respectively (p<0.002). CONCLUSIONS: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.

Fetal brain MR angiography at 1.5 T: a feasible study.

PURPOSE: The use of magnetic resonance angiography (MRA) for assessing CNS fetal vasculature has been limited. The aim of this study was to determine the feasibility and added value of 2D time-of-flight (TOF) MRA of the fetal brain vasculature with a 1.5 T scanner. METHODS: We conducted a prospective study (September 2018 to October 2022) by consecutively selecting pregnant women (≥ 18 years) with clinical indication to fetal brain MRI. On a 1.5 T scanner, a 2D TOF MRA acquisition was obtained at the end of the clinical protocol. Two neuroradiologists independently reviewed all MRIs; a qualitative scale of motion artifacts was applied to MRA images; represented vessels in MRA and T2 images were registered. RESULTS: Thirty-five fetal brain MRIs. Mean maternal age: 32 years; mean fetal gestational age (GA): 31 weeks. Artifacts were found in 74% of MRA. The number of MRAs performed without artifacts increased with GA. On MRA, the identification of the majority of vessels increased with GA; statistical significance was reached in the identification of torcular Herophili (p = 0.026), vein of Galen (p < 0.001), internal cerebral veins (p = 0.002), basilar artery (p = 0.027), vertebral arteries (p = 0.025), and middle cerebral arteries (p = 0.044). Significantly, MRA depicted the sigmoid sinuses and internal jugular veins more frequently. Vascular pathology was found in 3/35 fetal brain MRIs. CONCLUSION: Although artifacts were found in 74% of cases, MRA acquisitions were informative and of sufficient diagnostic quality in most studies. This technique may represent a valuable complimentary tool in CNS prenatal vascular studies.

Deep learning-based algorithm for postoperative glioblastoma MRI segmentation: a promising new tool for tumor burden assessment.

OBJECTIVE: Clinical and surgical decisions for glioblastoma patients depend on a tumor imaging-based evaluation. Artificial Intelligence (AI) can be applied to magnetic resonance imaging (MRI) assessment to support clinical practice, surgery planning and prognostic predictions. In a real-world context, the current obstacles for AI are low-quality imaging and postoperative reliability. The aim of this study is to train an automatic algorithm for glioblastoma segmentation on a clinical MRI dataset and to obtain reliable results both pre- and post-operatively. METHODS: The dataset used for this study comprises 237 (71 preoperative and 166 postoperative) MRIs from 71 patients affected by a histologically confirmed Grade IV Glioma. The implemented U-Net architecture was trained by transfer learning to perform the segmentation task on postoperative MRIs. The training was carried out first on BraTS2021 dataset for preoperative segmentation. Performance is evaluated using DICE score (DS) and Hausdorff 95% (H95). RESULTS: In preoperative scenario, overall DS is 91.09 (± 0.60) and H95 is 8.35 (± 1.12), considering tumor core, enhancing tumor and whole tumor (ET and edema). In postoperative context, overall DS is 72.31 (± 2.88) and H95 is 23.43 (± 7.24), considering resection cavity (RC), gross tumor volume (GTV) and whole tumor (WT). Remarkably, the RC segmentation obtained a mean DS of 63.52 (± 8.90) in postoperative MRIs. CONCLUSIONS: The performances achieved by the algorithm are consistent with previous literature for both pre-operative and post-operative glioblastoma's MRI evaluation. Through the proposed algorithm, it is possible to reduce the impact of low-quality images and missing sequences.

Association of MRI leptomeningeal enhancement with disability worsening in progressive multiple sclerosis: A clinical and post-mortem study.

BACKGROUND: Leptomeningeal enhancement (LME) has been described as a biomarker of meningeal inflammation in multiple sclerosis (MS). OBJECTIVE: The aim of this study was to (1) assess if LME is predictive of disability worsening in progressive MS (pMS) patients and (2) investigate the pathological substrates of LME in an independent post-mortem MS series. METHODS: In total, 115 pMS patients were imaged yearly with 1.5T MRI, using post-contrast CUBE 3D FLAIR for LME detection. Endpoint: to identify the baseline variables predictive of confirmed disability worsening (CDW) at 24 months follow-up. Post-mortem, inflammation, and structural changes of the leptomeninges were assessed in 12 MS/8 control brains. RESULTS: LME (27% of patients at baseline) was associated with higher EDSS and lower brain volume (nBV). LME was unchanged in most patients over follow-up. LME at baseline MRI was independently associated with higher risk of 24 months CDW (HR 3.05, 95% CI 1.36-6.84, p = 0.007) in a Cox regression, including age, nBV, T2 lesion volume, high-efficacy treatments, and MRI disease activity. Post-mortem, focal structural changes (fibrosis) of the leptomeninges were observed in MS, usually associated with inflammation (Kendall's Tau 0.315, p < 0.0001). CONCLUSIONS: LME is frequently detected in pMS patients using 1.5T MRI and is independently predictive of disability progression. LME could result from both focal leptomeningeal post-inflammatory fibrosis and inflammation.

Common and Uncommon CT Findings in CVID-Related GL-ILD: Correlations with Clinical Parameters, Therapeutic Decisions and Potential Implications in the Differential Diagnosis.

PURPOSE: To investigate computed tomography (CT) findings of Granulomatous Lymphocytic Interstitial Lung Disease (GL-ILD) in Common Variable Immunodeficiency (CVID), also in comparison with non-GL-ILD abnormalities, correlating GL-ILD features with functional/immunological parameters and looking for GL-ILD therapy predictive elements. METHODS: CT features of 38 GL-ILD and 38 matched non-GL-ILD subjects were retrospectively described. Correlations of GL-ILD features with functional/immunological features were assessed. A logistic regression was performed to find a predictive model of GL-ILD therapeutic decisions. RESULTS: Most common GL-ILD CT findings were bronchiectasis, non-perilymphatic nodules, consolidations, Ground Glass Opacities (GGO), bands and enlarged lymphnodes. GL-ILD was usually predominant in lower fields. Multiple small nodules (≤10 mm), consolidations, reticulations and fibrotic ILD are more indicative of GL-ILD. Bronchiectasis, GGO, Reticulations and fibrotic ILD correlated with decreased lung performance. Bronchiectasis, GGO and fibrotic ILD were associated with low IgA levels, whereas high CD4+ T cells percentage was related to GGO. Twenty out of 38 patients underwent GL-ILD therapy. A model combining Marginal Zone (MZ) B cells percentage, IgA levels, lower field consolidations and lymphnodes enlargement showed a good discriminatory capacity with regards to GL-ILD treatment. CONCLUSIONS: GL-ILD is a lower field predominant disease, commonly characterized by bronchiectasis, non-perilymphatic small nodules, consolidations, GGO and bands. Multiple small nodules, consolidations, reticulations and fibrotic ILD may suggest the presence of GL-ILD in CVID. MZ B cells percentage, IgA levels at diagnosis, lower field consolidations and mediastinal lymphnodes enlargement may predict the need of a specific GL-ILD therapy.

Tracheal atypical solitary carcinoid in a so called "difficult asthma": a diagnostic challenge.

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention having a diagnosis of "difficult asthma" from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. An HRCT scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort.

BACKGROUND: Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time. We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008-2021), with the evaluation of all children managed for acute encephalitis. METHODS: We retrospectively reviewed clinical, laboratory, neuroradiological, and EEG data from the acute phase and outcome of all immunocompetent patients diagnosed with acute encephalitis. According to the newly proposed criteria for pediatric autoimmune encephalitis, we divided patients into infectious, definite autoimmune, probable autoimmune, and possible autoimmune, and performed a comparison between the different groups. RESULTS: 48 patients (26 females, mean age 4.4 years), 19 with infections, and 29 with autoimmune encephalitis, were included. Herpes simplex virus 1 encephalitis was the most frequently identified etiology followed by anti-NMDA receptor encephalitis. Movement disorders at onset and a longer hospital stay were observed more frequently in autoimmune compared to infectious encephalitis (p p < 0.001 and p = 0.001, respectively). Among the autoimmune group, children who started immunomodulatory treatment earlier (within 7 days from onset) had more frequent complete functional recovery (p = 0.002). CONCLUSIONS: Herpes virus and anti-NMDAR encephalitis are the most frequent etiologies within our cohort. Clinical onset and course are extremely variable. Since early immunomodulatory treatment was associated with a better functional outcome, our data confirm that a timely diagnostic classification in definite, probable, or possible autoimmune encephalitis can help the clinician in a successful therapeutic approach.

Pancreatic cancer detection with a non-contrast MR protocol: is it reliable?

PURPOSE: The pancreatic cancer (PC) is the 4th leading cancer-related death, becoming the second one by 2030, with a 5 year survival rate of 8%. Considering its increased incidence in high-risk categories compared to the general population, we aimed to validate a non-contrast MR protocol, to detect PC in its earliest phase, which could be suitable as a screening tool in high-risk patients. MATERIALS AND METHODS: In this retrospective study, we selected 200 patients (> 40 years) from our radiological database, which performed upper abdominal MRI between 2012 and 2017. 100 were negative for pancreatic lesions and 100 positive for pancreatic lesion (< 30 mm). The latter group included: 40 PDAC (pancreatic adenocarcinoma), 42 BD-IPMN (Branch Duct- Intraductal Papillary Mucinous Neoplasm), 10 PNET(pancreatic neuroendocrine tumor), 4 SCN(serous cystic neoplasm), 3 IPS(intrapancreatic spleen), 1 MCN(mucinous cystic neoplasm). Three readers (R1, R2 and R3) with a high, medium and low experience, respectively, analysed, first, the non-contrast MR sequences (single-shot T2w breath-hold, GE T1w FS, DWI and 2D/3D MRCP), and then the standard MR protocol, independently, randomly and anonymously. Readers identified or excluded the presence of pancreatic lesion, in both reading sessions. These results were compared with the histopathological diagnosis, and then divided into 3 different classes of lesions: all lesions, pancreatic adenocarcinoma and solid lesion. Mcnemar's test was used to compare the results. The inter-observer agreement was determined according to the kappa statistic in both protocols, and then the inter-protocol agreement was calculated. RESULTS: The non-contrast MR protocol has reached statistical parameters values ranging between 83% in SE (sensitivity) by R3 and 99% in NPV (negative predictive value) by R1. The standard MR protocol has reported slight increasing statistical parameters compared to those of the proposed one. However, there are not significant statistical differences between the both protocols. The proposed non-contrast MR protocol has reported the highest NPVs in the PDAC group detection (R1: 99%, R2: 99%, R3: 98%). In all groups of lesions, the agreement between the two protocols was excellent for each Reader ranging from 96 to 98%. CONCLUSION: The proposed non-contrast MR protocol showed high PC detection values and a time execution ≤ 20 min. Therefore, it can be proposed as a screening tool in high-risk patients.

Radiology-based diagnosis of fungal pulmonary infections in high-risk hematology patients: are we making progress?

PURPOSE OF REVIEW: In patients with hematological malignancies, high-resolution computed tomography (CT) is the recommended imaging approach for diagnosis, staging and monitoring of invasive fungal disease (IFD) but lacks specificity. We examined the status of current imaging modalities for IFD and possibilities for more effective applications of current technology for improving the specificity of IFD diagnosis. RECENT FINDINGS: Although CT imaging recommendations for IFD are largely unchanged in the last 20 years, improvements in CT scanner technology and image processing algorithms now allow for technically adequate examinations at much lower radiation doses. CT pulmonary angiography can improve both the sensitivity and specificity of CT imaging for angioinvasive molds in both neutropenic and nonneutropenic patients, through detection of the vessel occlusion sign (VOS). MRI-based approaches also show promise not only for early detection of small nodules and alveolar hemorrhage but can also be used to detect pulmonary vascular occlusion without radiation and iodinated contrast media. 18F-fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) is increasingly used to monitor long-term treatment response for IFD, but could become a more powerful diagnostic tool with the development of fungal-specific antibody imaging tracers. SUMMARY: High-risk hematology patients have a considerable medical need for more sensitive and specific imaging approaches for IFD. This need may be addressable, in part, by better exploiting recent progress in CT/MRI imaging technology and algorithms to improve the specificity of radiological diagnosis for IFD.

Towards an Automated Approach to the Semi-Quantification of [18F]F-DOPA PET in Pediatric-Type Diffuse Gliomas.

BACKGROUND: This study aims to evaluate the use of a computer-aided, semi-quantification approach to [18F]F-DOPA positron emission tomography (PET) in pediatric-type diffuse gliomas (PDGs) to calculate the tumor-to-background ratio. METHODS: A total of 18 pediatric patients with PDGs underwent magnetic resonance imaging and [18F]F-DOPA PET, which were analyzed using both manual and automated procedures. The former provided a tumor-to-normal-tissue ratio (TN) and tumor-to-striatal-tissue ratio (TS), while the latter provided analogous scores (tn, ts). We tested the correlation, consistency, and ability to stratify grading and survival between these methods. RESULTS: High Pearson correlation coefficients resulted between the ratios calculated with the two approaches: ρ = 0.93 (p < 10-4) and ρ = 0.814 (p < 10-4). The analysis of the residuals suggested that tn and ts were more consistent than TN and TS. Similarly to TN and TS, the automatically computed scores showed significant differences between low- and high-grade gliomas (p ≤ 10-4, t-test) and the overall survival was significantly shorter in patients with higher values when compared to those with lower ones (p < 10-3, log-rank test). CONCLUSIONS: This study suggested that the proposed computer-aided approach could yield similar results to the manual procedure in terms of diagnostic and prognostic information.

Syringomyelia Associated with Chiari 1 Malformation in Adults: Positive Outcome Predictors after Posterior Fossa Decompression with Duraplasty.

BACKGROUND: Syringomyelia (Syr) in patients with Chiari 1 malformation (CM1) may be attributable to abnormal dynamics of cerebrospinal fluid (CSF) in the upper cervical segment; fourth ventricle enlargement has been reported in association with a worse clinical and radiological presentation, independently of the posterior fossa volume. In this study, we analyzed presurgery hydrodynamic markers to evaluate if their changes could be associated with clinical and radiological improvement after posterior fossa decompression and duraplasty (PFDD). As a primary endpoint, we aimed to correlate improvement in the fourth ventricle area with positive clinical outcomes. METHODS: In total, in this study, we enrolled 36 consecutive adults with Syr and CM1 who were followed by a multidisciplinary team. All the patients were prospectively evaluated with clinical scales and neuroimaging, including CSF flow, the fourth ventricle area, and the Vaquero Index by using a phase-contrast MRI before (T0) and after surgical treatment (T1-Tlast, with a range of 12-108 months). The CSF flow at the craniocervical junction (CCJ), the fourth ventricle area, and the Vaquero Index changes were statistically analyzed and compared to the clinical and quality of life improvement after surgery. The good outcome prediction ability of presurgical radiological variables was tested. RESULTS: Surgery was associated with positive clinical and radiological outcomes in more than 90% of cases. The fourth ventricle area significantly reduced after surgery (T0-Tlast, p = 0.0093), but no significant associations with clinical improvement were found. The presurgical presence of CSF flow at the CCJ was able to predict a good outcome (AUC = 0.68, 95% CI 0.50-0.87 and LH+ = 2.1, IC 95% 1.16-3.07) and was also significantly associated with post-surgical pain relief (rho = 0.61 and p = 0.0144). CONCLUSIONS: Presurgery CSF flow at the CCJ is proposed as a radiological marker with the ability to predict a positive outcome after PFDD in adults with syringomyelia and CM1. Measurements of the fourth ventricle area could be useful additional information for evaluating surgical long-term follow-up; further experience on larger cohorts is required to better define the prognostic yield of this radiological parameter.

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma.

Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.

Ultrashort Echo-Time Magnetic Resonance Imaging Sequence in the Assessment of Systemic Sclerosis-Interstitial Lung Disease.

PURPOSE: To test respiratory-triggered ultrashort echo-time (UTE) Spiral VIBE-MRI sequence in systemic sclerosis-interstitial lung disease assessment compared with computed tomography (CT). MATERIAL AND METHODS: Fifty four SSc patients underwent chest CT and UTE (1.5 T). Two radiologists, independently and in consensus, verified ILD presence/absence and performed a semiquantitative analysis (sQA) of ILD, ground-glass opacities (GGO), reticulations and honeycombing (HC) extents on both scans. A CT software quantitative texture analysis (QA) was also performed. For ILD detection, intra-/inter-reader agreements were computed with Cohen K coefficient. UTE sensitivity and specificity were assessed. For extent assessments, intra-/inter-reader agreements and UTE performance against CT were computed by Lin's concordance coefficient (CCC). RESULTS: Three UTE were discarded for low quality, 51 subjects were included in the study. Of them, 42 QA segmentations were accepted. ILD was diagnosed in 39/51 CT. UTE intra-/inter-reader K in ILD diagnosis were 0.56 and 0.26. UTE showed 92.8% sensitivity and 75.0% specificity. ILD, GGO, and reticulation extents were 14.8%, 7.7%, and 7.1% on CT sQA and 13.0%, 11.2%, and 1.6% on CT QA. HC was <1% and not further considered. UTE intra-/inter-reader CCC were 0.92 and 0.89 for ILD extent and 0.84 and 0.79 for GGO extent. UTE RET extent intra-/inter-reader CCC were 0.22 and 0.18. UTE ILD and GGO extents CCC against CT sQA and QA were ≥0.93 and ≥0.88, respectively. RET extent CCC were 0.35 and 0.22 against sQA and QA, respectively. CONCLUSION: UTE Spiral VIBE-MRI sequence is reliable in assessing ILD and GGO extents in systemic sclerosis-interstitial lung disease patients.

Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas.

PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

Early molecular diagnosis of BRAF status drives the neurosurgical management in BRAF V600E-mutant pediatric low-grade gliomas: a case report.

BACKGROUND: To date, this is the only report showing with close and consecutive magnetic resonance images the extremely rapid response of two types of pediatric low-grade gliomas (PLGG) to vemurafenib and its impact on the surgical approach. CASES PRESENTATION: We report two cases of symptomatic PLGG treated with vemurafenib, a BRAF inhibitor: in a 12-year-old girl it was used as first-line medical treatment, reducing the tumor by 45% within a month and stabilizing to 76% after a year; in a 3-year-old boy with no improvement after SIOP LGG 2004 Protocol, vemurafenib induced in only one week a 34% shrinkage and solved the hydrocephalus, avoiding surgical operation. DISCUSSION AND CONCLUSIONS: Our cases demonstrate how an early molecular diagnosis of BRAF mutations through the neurosurgical biopsy is essential to promptly start targeted therapies., whose effect can influence both therapeutic and surgical decisions, hopefully reducing the occurrence of second neurosurgery with associated risks of neurological sequelae.

Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging.

This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring.