Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging: Feasibility and challenges.

The integration of 7 Tesla magnetic resonance imaging (7 T MRI) in adult patients has marked a revolutionary stride in radiology. In this article we explore the feasibility of 7 T MRI in paediatric practice, emphasizing its feasibility, applications, challenges, and safety considerations. The heightened resolution and tissue contrast of 7 T MRI offer unprecedented diagnostic accuracy, particularly in neuroimaging. Applications range from neuro-oncology to neonatal brain imaging, showcasing its efficacy in detecting subtle structural abnormalities and providing enhanced insights into neurological conditions. Despite the promise, challenges such as high cost, discomfort, and safety concerns necessitate careful consideration. Research suggests that, with precautions, 7 T MRI is feasible in paediatrics, yet ongoing studies and safety assessments are imperative.

Neuroradiological manifestations in hospitalized patients with COVID-19: An Italian national multicenter study on behalf of AINR (Associazione Italiana di Neuroradiologia) and SIRM (Società Italiana di Radiologia Medica).

PURPOSE: This multicentric study aims to characterize and assess the occurrence of neuroradiological findings among patients with SARS-CoV-2 infection during the first Italian wave of the pandemic outbreak. MATERIALS AND METHODS: Patients' data were collected between May 2020 and June 2020. Clinical and laboratory data, chest imaging, brain CT, and MRI imaging were included. Acquired data were centralized and analyzed in two hospitals: ASST Spedali Civili, Brescia, and IRRCS San Raffaele Research Hospital, Milan, Italy. COVID-19 patients were classified into two different subgroups, vascular and nonvascular. The vascular pattern was further divided into ischemic and hemorrhagic stroke groups. RESULTS: Four hundred and fifteen patients from 20 different Italian Centers were enrolled in the study. The most frequent symptom was focal neurological deficit, found in 143 patients (34.5%). The most frequent neuroradiological finding was ischemic stroke in 122 (29.4%) patients. Forty-four (10.6%) patients presented a cerebral hemorrhage. Forty-seven patients had non-stroke neuroimaging lesions (11.3%). The most common was PRES-like syndrome (28%), SWI hypointensities (22%), and encephalitis (19%). The stroke group had higher CAD risk (37.5% vs 20%, p = .016) and higher D-dimer levels (1875 ng/mL vs 451 ng/mL, p < .001) compared to the negative group. CONCLUSION: Our study describes the biggest cohort study in Italy on brain imaging of COVID-19 patients and confirms that COVID-19 patients are at risk of strokes, possibly due to a pro-thrombotic microenvironment. Moreover, apart from stroke, the other neuroradiological patterns described align with the ones reported worldwide.

Supramaximal resection: retrospective study on IDH-wildtype Glioblastomas based on the new RANO-Resect classification.

BACKGROUND: The prognostic value of the extent of resection in the management of Glioblastoma is a long-debated topic, recently widened by the 2022 RANO-Resect Classification, which advocates for the resection of the non-enhancing disease surrounding the main core of tumors (supramaximal resection, SUPR) to achieve additional survival benefits. We conducted a retrospective analysis to corroborate the role of SUPR by the RANO-Resect Classification in a single center, homogenous cohort of patients. METHODS: Records of patients operated for WHO-2021 Glioblastomas at our institution between 2007 and 2018 were retrospectively reviewed; volumetric data of resected lesions were computed and classified by RANO-Resect criteria. Survival and correlation analyses were conducted excluding patients below near-total resection. RESULTS: 117 patients met the inclusion criteria, encompassing 45 near-total resections (NTR), 31 complete resections (CR), and 41 SUPR. Median progression-free and overall survival were 11 and 15 months for NTR, 13 and 17 months or CR, 20 and 24 months for SUPR, respectively (p < 0.001), with inverse correlation observed between survival and FLAIR residual volume (r -0.28). SUPR was not significantly associated with larger preoperative volumes or higher rates of postoperative deficits, although it was less associated with preoperative neurological deficits (OR 3.37, p = 0.003). The impact of SUPR on OS varied between MGMT unmethylated (HR 0.606, p = 0.044) and methylated (HR 0.273, p = 0.002) patient groups. CONCLUSIONS: Results of the present study support the validity of supramaximal resection by the new RANO-Resect classification, also highlighting a possible surgical difference between tumors with methylated and unmethylated MGMT promoter.

CT Cadaveric dataset for Radiomics features stability assessment in lumbar vertebrae.

Radiomics features (RFs) studies have showed limitations in the reproducibility of RFs in different acquisition settings. To date, reproducibility studies using CT images mainly rely on phantoms, due to the harness of patient exposure to X-rays. The provided CadAIver dataset has the aims of evaluating how CT scanner parameters effect radiomics features on cadaveric donor. The dataset comprises 112 unique CT acquisitions of a cadaveric truck acquired on 3 different CT scanners varying KV, mA, field-of-view, and reconstruction kernel settings. Technical validation of the CadAIver dataset comprises a comprehensive univariate and multivariate GLM approach to assess stability of each RFs extracted from lumbar vertebrae. The complete dataset is publicly available to be applied for future research in the RFs field, and could foster the creation of a collaborative open CT image database to increase the sample size, the range of available scanners, and the available body districts.

From strength to precision: A systematic review exploring the clinical utility of 7-Tesla magnetic resonance imaging in abdominal imaging.

BACKGROUND: After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated the feasibility as well as diagnostic capabilities of liver, kidney, and prostate MRI at 7-Tesla. However, the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks, primarily stemming from heightened artifacts and limitations in Specific Absorption Rate, etc. Furthermore, evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence. AIM: To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends, details relevant challenges, and provides a concise set of potential solutions. METHODS: This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A PubMed search, utilizing Medical Subject Headings terms such as "7-Tesla" and organ-specific terms, was conducted for articles published between January 1, 1985, and July 25, 2023. Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs, encompassing various study types (in-vivo/ex-vivo, method development, reviews/meta-analyses). Exclusion criteria involved animal studies and those lacking extractable data. Study selection involved initial identification via title/abstract, followed by a full-text review by two researchers, with discrepancies resolved through discussion. Data extraction covered publication details, study design, population, sample size, 7T MRI protocol, image characteristics, endpoints, and conclusions. RESULTS: The systematic review included a total of 21 studies. The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate (n = 8), followed by the kidney (n = 6) and the hepatobiliary system (n = 5). Studies on these organs, and in the pancreas, demonstrated clear advantages at 7T. However, small bowel studies showed no significant improvements compared to traditional MRI at 1.5T. The majority of studies evaluated originated from Germany (n = 10), followed by the Netherlands (n = 5), the United States (n = 5), Austria (n = 2), the United Kingdom (n = 1), and Italy (n = 1). CONCLUSION: Further increase of abdominal clinical MRI field strength to 7T demonstrated high imaging potential, yet also limitations mainly due to the inhomogeneous radiofrequency (RF) excitation field relative to lower field strengths. Hence, further optimization of dedicated RF coil elements and pulse sequences are expected to better optimize clinical imaging at high magnetic field strength.

An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.

The role of preoperative [11C]methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas.

OBJECTIVE: Surgery is the mainstay of treatment for low-grade glioma (LGG)-related epilepsy. However, the goal of achieving both oncological radical resection and seizure freedom can be challenging. PET with [11C]methionine (MET) has been recently introduced in clinical practice for the management of patients with LGGs, not only to monitor the response to treatments, but also as a preoperative tool to define the metabolic tumor extent and to predict tumor grading, type, and prognosis. Still, its role in defining tumor-related epilepsy and postoperative seizure outcomes is limited. The aim of this preliminary study was to investigate the role of MET PET in defining preoperative seizure characteristics and short-term postoperative seizure control in a cohort of patients with newly diagnosed temporal lobe low-grade gliomas (tLGGs). METHODS: Patients with newly diagnosed and histologically proven temporal lobe grade 2/3 gliomas (2021 WHO CNS tumor classification) who underwent resection at the authors' institution between July 2011 and March 2021 were included in this retrospective study. MET PET images were acquired, fused with MRI scans, and qualitatively and semiquantitatively analyzed. Any eventual PET/MRI involvement of the temporomesial area, seizure characteristics, and 1-year seizure outcomes were reported. RESULTS: A total of 52 patients with tLGGs met the inclusion criteria. MET PET was positive in 41 (79%) patients, with a median metabolic tumor volume of 14.56 cm3 (interquartile range [IQR] 6.5-28.2 cm3). The median maximum and mean tumor-to-background ratio (TBRmax, TBRmean) were 2.24 (IQR 1.58-2.86) and 1.53 (IQR 1.37-1.70), respectively. The metabolic tumor volume was found to be related to the presence of seizures at disease onset, but only in noncodeleted tumors (p = 0.014). Regarding patients with uncontrolled seizures at surgery, only the temporomesial area PET involvement showed a statistical correlation both in the univariate (p = 0.058) and in the multivariate analysis (p = 0.030). At 1-year follow-up, seizure control was correlated with MET PET-derived semiquantitative data. Particularly, higher TBRmax (p = 0.0192) and TBRmean (p = 0.0128) values were statistically related to uncontrolled seizures 1 year after surgery. CONCLUSIONS: This preliminary study suggests that MET PET may be used as a preoperative tool to define seizure characteristics and outcomes in patients with tLGGs. These findings need to be further validated in larger series with longer epileptological follow-ups.

The gut-brain axis: Correlation of choroid plexus volume and permeability with inflammatory biomarkers in Crohn's disease.

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.

Quantification of cauda equina nerve root dispersion through radiomics features in weight-bearing MRI in normal subjects and spinal canal stenosis patients.

OBJECTIVE: To quantify the distribution of cauda equina nerve roots in supine and upright positions using manual measurements and radiomics features both in normal subjects and in lumbar spinal canal stenosis (LSCS) patients. METHODS: We retrospectively recruited patients who underwent weight-bearing MRI in supine and upright positions for back pain. 3D T2-weighted isotropic acquisition (3D-HYCE) sequences were used to develop a 3D convolutional neural network for identification and segmentation of lumbar vertebrae. Para-axial reformatted images perpendicular to the spinal canal and parallel to each vertebral endplate were automatically extracted. From each level, we computed the maximum antero-posterior (AP) and latero-lateral (LL) dispersion of nerve roots; further, radiomics features were extracted to quantify standardized metrics of nerve root distribution. RESULTS: We included 16 patients with LSCS and 20 normal subjects. In normal subjects, nerve root AP dispersion significantly increased from supine to upright position (p < 0.001, L2-L5 levels), and radiomics features showed an increase in non-uniformity. In LSCS subjects, in the upright position AP dispersion of nerve roots and entropy-related features increased caudally to the stenosis level (p < 0.001) and decreased cranially (p < 0.001). Moreover, entropy-related radiomics features negatively correlated with pre-operative Pain Numerical Rating Scale. Comparison between normal subjects and LSCS patients showed a difference in AP dispersion and increase of variance cranially to the stenosis level (p < 0.001) in the upright position. CONCLUSIONS: Nerve root distribution inside the dural sac changed between supine and upright positions, and radiomics features were able to quantify the differences between normal and LSCS subjects. CLINICAL RELEVANCE STATEMENT: The distribution of cauda equina nerve roots and the redundant nerve root sign significantly varies between supine and upright positions in normal subjects and spinal canal stenosis patients, respectively. Radiomics features quantify nerve root dispersion and correlates with pain severity. KEY POINTS: • Weight-bearing MRI depicts spatial distribution of the cauda equina in both supine and upright positions in normal subjects and spinal stenosis patients. • Radiomics features can quantify the effects of spinal stenosis on the dispersion of the cauda equina in the dural sac. • In the orthostatic position, dispersion of nerve roots is different in lumbar spinal stenosis patients compared to that in normal subjects; entropy-related features negatively correlated with pre-operative Pain Numerical Rating Scale.

The lumbar adjacent-level syndrome: analysis of clinical, radiological, and surgical parameters in a large single-center series.

OBJECTIVE: The development of specific clinical and neurological symptoms and radiological degeneration affecting the segment adjacent to a spinal arthrodesis comprise the framework of adjacent-level syndrome. Through the analysis of a large surgical series, this study aimed to identify possible demographic, clinical, radiological, and surgical risk factors involved in the development of adjacent-level syndrome. METHODS: A single-center retrospective analysis of adult patients undergoing lumbar fusion procedures between January 2014 and December 2018 was performed. Clinical, demographic, radiological, and surgical data were collected. Patients who underwent surgery for adjacent-segment disease (ASD) were classified as the ASD group. All patients were evaluated 1 month after the surgical procedure clinically and radiologically (with lumbar radiographs) and 3 months afterward with CT scans. The last follow-up was performed by telephone interview. The median follow-up for patients included in the analysis was 67.2 months (range 39-98 months). RESULTS: A total of 902 patients were included in this study. Forty-nine (5.4%) patients required reoperation for ASD. A significantly higher BMI value was observed in the ASD group (p < 0.001). Microdiscectomy and microdecompression procedures performed at the upper or lower level of an arthrodesis without fusion extension have a statistically significant impact on the development of ASD (p = 0.001). Postoperative pelvic tilt in the ASD group was higher than in the non-ASD group. Numeric rating scale, Core Outcome Measures Index, and Oswestry Disability Index scores at the last follow-up were significantly higher in patients in the ASD group and in patients younger than 65 years. CONCLUSIONS: Identifying risk factors for the development of adjacent-level syndrome allows the implementation of a prevention strategy in patients undergoing lumbar arthrodesis surgery. Age older than 65 years, high BMI, preexisting disc degeneration at the adjacent level, and high postoperative pelvic tilt are the most relevant factors. In addition, patients older than 65 years achieve higher levels of clinical improvement and postsurgical satisfaction than do younger patients.

CT-based radiomics can identify physiological modifications of bone structure related to subjects' age and sex.

PURPOSE: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. MATERIALS AND METHODS: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. RESULTS: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). CONCLUSION: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.

Case report: Reversible punctate inflammatory foci in the corpus callosum: A novel radiological finding of CAR T-cell therapy-related neurotoxicity.

Introduction: Chimeric antigen receptor T-cell therapy-related neurotoxicity is a novel cytokine-mediated neurological syndrome that may present with a broad spectrum of manifestations. Descriptions of novel distinctive features are pivotal to untangling this condition's clinical and instrumental signature in order to inform diagnosis and pathophysiology. Case: A 27-year-old female patient received anti-CD19 CAR T cells for a refractory primary mediastinal B-cell lymphoma. At 6 days after the infusion, she developed mild ideo-motor slowing, dysgraphia, and drowsiness. Despite specific treatment with dexamethasone, her neurological status progressively worsened to a comatose state within 24 h. EEG and CSF analyses were non-specific, showing background slowing and inflammatory findings. Brain MRI revealed multiple focal punctate areas of T2-weighted hyperintensity localized in the body and isthmus of the corpus callosum. Following the administration of high-dose intravenous methylprednisolone, her neurological status resolved within 48 h. Notably, the follow-up brain MRI did not reveal any abnormalities in the corpus callosum, except for a reduction of fractional anisotropy. Conclusion: Reversible punctate inflammatory foci of the body and isthmus of the corpus callosum may represent a novel radiological finding of CAR T-cell therapy-related neurotoxicity.

Editorial comment: Radiogenomics of glioblastoma: shifting the focus from tumor cells to immune microenvironment.

KEY POINTS: • The ICI score derived from gene expression profile of immune cells infiltrating GBM correlates with overall survival and is an effective prognostic biomarker.• In this study, the authors developed a radiomics-based machine learning model able to identify gene expression profiles of GBM intratumoral stromal and immune cells and predict the ICI score on the preoperative MRI scans with high accuracy.• Radiogenomics could potentially be applied in primary brain tumors to noninvasively assess the specific tumor immune characteristics, predict patients' prognosis and identify those patients with higher probability to respond to immunotherapy.

Antibody Titer Correlates with Omicron Infection in Vaccinated Healthcare Workers.

The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies.

Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial.

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.