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Background and Objectives: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability., Methods: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed. Physical and cognitive disabilities were assessed with the expanded disability status scale (EDSS) and the symbol digit modalities test (SDMT), respectively. Demyelinating lesions were automatically segmented, and the corresponding masks were used to assess pairwise structural disconnection between atlas-defined brain regions based on normative tractography data. Using the Morphometric Inverse Divergence method, we computed morphometric similarity between cortical regions based on FreeSurfer surface reconstruction. Using network-based statistics (NBS) and its extension NBS-predict, we tested whether subject-level connectomes were associated with disease status, progression, clinical disability, and long-term confirmed disability progression (CDP), independently from global lesion burden and atrophy., Results: We studied 461 pwMS (age = 37.2 ± 10.6 years, F/M = 324/137), corresponding to 1,235 visits (mean follow-up time = 1.9 ± 2.0 years, range = 0.1-13.3 years), and 55 HC (age = 42.4 ± 15.7 years; F/M = 25/30). Long-term clinical follow-up was available for 285 pwMS (mean follow-up time = 12.4 ± 2.8 years), 127 of whom (44.6%) exhibited CDP. At baseline, structural disconnection in pwMS was mostly centered around the thalami and cortical sensory and association hubs, while morphometric similarity was extensively disrupted ( p FWE < 0.01). EDSS was related to frontothalamic disconnection ( p FWE < 0.01) and disrupted morphometric similarity around the left perisylvian cortex ( p FWE = 0.02), while SDMT was associated with cortico-subcortical disconnection in the left hemisphere ( p FWE < 0.01). Longitudinally, both structural disconnection and morphometric similarity disruption significantly progressed ( p FWE = 0.04 and p FWE < 0.01), correlating with EDSS increase (ρ = 0.07, p = 0.02 and ρ = 0.11, p < 0.001), while baseline disconnection predicted long-term CDP (accuracy = 59% [58-60], p = 0.03)., Discussion: Structural disconnection and morphometric similarity networks, as assessed through conventional MRI, are sensitive to MS-related brain damage and its progression. They explain disease-related clinical disability and predict its long-term evolution independently from global lesion burden and atrophy, potentially adding to established MRI measures as network-based biomarkers of disease severity and progression.

An innovative multicompartmental anatomic brain phantom (StepBrain) is described to simulate the in vivo tracer uptake of gray matter, white matter, and striatum, overcoming the limitations of currently available phantoms. Methods: StepBrain was created by exploiting the potential of fused deposition modeling 3-dimensional printing to replicate the real anatomy of the brain compartments, as modeled through ad hoc processing of healthy-volunteer MR images. Results: A realistic simulation of 18 F-FDG PET brain studies, using target activity to obtain the real concentration ratios, was obtained, and the results of postprocessing with partial-volume effect correction tools developed for human PET studies confirmed the accuracy of these methods in recovering the target activity concentrations. Conclusion: StepBrain compartments (gray matter, white matter, and striatum) can be simultaneously filled, achieving different concentration ratios and allowing the simulation of different (e.g., amyloid, tau, or 6-fluoro-l-dopa) tracer distributions, with a potentially valuable role for multicenter PET harmonization studies., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical-radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development. This review paper aims to provide a comprehensive framework for a better understanding of the present and future potential applications of neuroimaging techniques for evaluating nonsyndromic CRS, highlighting strategies for optimizing their use in clinical practice and offering an overview of the most relevant technological advancements in terms of diagnostic performance, radiation exposure, and cost-effectiveness.

Objective: To measure the size of jugular foramina in infants affected by external hydrocephalus (EH) and in a control group, to support the hypothesis that a jugular foramen (JF) stenosis may determine dural venous sinus alterations and increased venous outflow resistance as main pathophysiological factor., Methods: Minimum, maximum, and mean values of JF areas were measured in a series of phase-contrast magnetic resonance venous angiography (angio MRV PCA3D) performed on 81 infants affected by EH. Results were compared with a group of 54 controls., Results: Smaller JF area was significantly smaller in patients versus controls (43.1 ± 14.6 vs. 52.7 ± 17.8; p < 0.001) resulting in a significantly smaller mean JF areas in patients vs. controls (51.6 ± 15.8 vs. 57.0 ± 18.3; p = 0.043). In patients, smaller JF areas were significantly associated with higher venous obstruction grading score (VOGS) both on the right (p = 0.018) and on the left side (p = 0.005). Positional plagiocephaly (cranial vault asymmetry index > 3.5%) was more frequent among EH patients than controls (38/17) but the difference was not significant (p = 0.07). In the 38 plagiocephalic patients, JF area was smaller on the flattened side than the contralateral in a significant number of cases both in right (21/7) and left (9/1) plagiocephaly (p < 0.0005) as well as the mean area (48.2 + 16.4 mm 2 vs. 57.5 + 20.7 mm 2 , p = 0.002) and VOGS was significantly higher on the plagiocephalic side than on the contralateral side (1.6 ± 1.1 vs. 1.1 ± 0.9, p = 0.019)., Conclusion: In this series of infants affected by EH, the mean size of the ostium of both JF resulted significantly smaller than controls. JF stenosis was significantly associated with higher degrees of venous obstruction on both sides, suggesting a direct extrinsic effect of JF size on dural sinus lumen and possible consequent effect on venous outflow resistance. Positional plagiocephaly, when present, was associated with a decreased JF area and increased VOGS on the flattened side., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Large-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting-state functional connectivity is characterized by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease. Brain flexibility has been recently found increased in multiple sclerosis, but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the multiple sclerosis clinical phenotypes remain unexplored so far. We performed a brain dynamics study quantifying brain flexibility utilizing the 'functional repertoire' (i.e. the number of configurations of active brain areas) through source reconstruction of magnetoencephalography signals in a cohort of 25 multiple sclerosis patients (10 relapsing-remitting multiple sclerosis and 15 secondary progressive multiple sclerosis) and 25 healthy controls. Multiple sclerosis patients showed a greater number of unique reconfigurations at fast time scales as compared with healthy controls. This difference was mainly driven by the relapsing-remitting multiple sclerosis phenotype, whereas no significant differences in brain dynamics were found between secondary progressive multiple sclerosis and healthy controls. Brain flexibility also showed a different predictive power on clinical disability according to the multiple sclerosis type. For the first time, we investigated brain dynamics in multiple sclerosis patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the multiple sclerosis phenotype and its relationship with clinical disability., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Multiple sclerosis (MS) is an autoimmune chronic disease characterized by inflammation and demyelination of the central nervous system (CNS). Despite numerous studies conducted, valid biomarkers enabling a definitive diagnosis of MS are not yet available. The aim of our study was to identify a marker from a blood sample to ease the diagnosis of MS. In this study, since there is evidence connecting the serotonin pathway to MS, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to detect serum MS-specific auto-antibodies (auto-Ab) against the extracellular loop 1 (ECL-1) of the 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A). We utilized an ELISA format employing poly-D-lysine as a pre-coating agent. The binding of 208 serum samples from controls, both healthy and pathological, and of 104 serum samples from relapsing-remitting MS (RRMS) patients was tested. We observed that the serum-binding activity in control cohort sera, including those with autoimmune and neurological diseases, was ten times lower compared to the RRMS patient cohort ( p = 1.2 × 10 -47 ), with a sensitivity and a specificity of 98% and 100%, respectively. These results show that in the serum of patients with MS there are auto-Ab against the serotonin receptor type 2A which can be successfully used in the diagnosis of MS due to their high sensitivity and specificity.

Background: Brain parenchyma (BP) and intracranial cerebrospinal fluid (iCSF) volumes measured by fully automated segmentation of clinical brain MRI studies may be useful for the diagnosis and follow-up of pediatric hydrocephalus. However, previously published segmentation techniques either rely on dedicated sequences, not routinely used in clinical practice, or on spatial normalization, which has limited accuracy when severe brain distortions, such as in hydrocephalic patients, are present., Purpose: We developed a fully automated method to measure BP and iCSF volumes from clinical brain MRI studies of pediatric hydrocephalus patients, exploiting the complementary information contained in T2- and T1-weighted images commonly used in clinical practice., Methods: The proposed procedure, following skull-stripping of the combined volumes, performed using a multiparametric method to obtain a reliable definition of the inner skull profile, maximizes the CSF-to-parenchyma contrast by dividing the T2w- by the T1w- volume after full-scale dynamic rescaling, thus allowing separation of iCSF and BP through a simple thresholding routine., Results: Validation against manual tracing on 23 studies (four controls and 19 hydrocephalic patients) showed excellent concordance (ICC > 0.98) and spatial overlap (Dice coefficients ranging from 77.2% for iCSF to 96.8% for intracranial volume). Accuracy was comparable to the intra-operator reproducibility of manual segmentation, as measured in 14 studies processed twice by the same experienced neuroradiologist. Results of the application of the algorithm to a dataset of 63 controls and 57 hydrocephalic patients (19 with parenchymal damage), measuring volumes' changes with normal development and in hydrocephalic patients, are also reported for demonstration purposes., Conclusions: The proposed approach allows fully automated segmentation of BP and iCSF in clinical studies, also in severely distorted brains, enabling to assess age- and disease-related changes in intracranial tissue volume with an accuracy comparable to expert manual segmentation., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Renal artery aneurysm (RAA) is a rare, often asymptomatic disease (0.1% incidence in general population) and can be incidentally diagnosed during an abdominal imaging workup. The traditional, gold standard of treatment is open surgery, carrying with it, however, a high risk of nephrectomy, mortality, and collateral morbidity. The endovascular approach is currently the most valid alternative to treating RAAs reducing, as it does, the risks associated with the surgical approach/open surgery. Herein we report on our experience with a case of wide-necked RAA treated with the Pipeline Vantage (Medtronic) flow diverter stent. Wide-neck aneurysms are defined as having neck diameters greater than 4 mm. Our choice of endovascular treatment was preferred over the surgical option notwithstanding the large size of the neck and the involvement of the branching vessels., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objectives: The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS., Methods: In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons., Results: MS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04)., Conclusions: We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition., Key Points: • Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus. • Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy. • Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation., (© 2022. The Author(s).)

Background: The clinical role of perfusion-weighted MRI (PWI) in head and neck squamous cell carcinoma (HNSCC) remains to be defined. The aim of this study was to provide evidence-based recommendations for the use of PWI sequence in HNSCC with regard to clinical indications and acquisition parameters., Methods: Public databases were searched, and selected papers evaluated applying the Oxford criteria 2011. A questionnaire was prepared including statements on clinical indications of PWI as well as its acquisition technique and submitted to selected panelists who worked in anonymity using a modified Delphi approach. Each panelist was asked to rate each statement using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Statements with scores equal or inferior to 5 assigned by at least two panelists were revised and re-submitted for the subsequent Delphi round to reach a final consensus., Results: Two Delphi rounds were conducted. The final questionnaire consisted of 6 statements on clinical indications of PWI and 9 statements on the acquisition technique of PWI. Four of 19 (21%) statements obtained scores equal or inferior to 5 by two panelists, all dealing with clinical indications. The Delphi process was considered concluded as reasons entered by panelists for lower scores were mainly related to the lack of robust evidence, so that no further modifications were suggested., Conclusions: Evidence-based recommendations on the use of PWI have been provided by an independent panel of experts worldwide, encouraging a standardized use of PWI across university and research centers to produce more robust evidence., (© 2022. The Author(s).)

To assess if the severity of nigrostriatal innervation loss affects the functional connectivity (FC) of the sensorimotor cortico-striato-thalamic-cortical loop (CSTCL) in Parkinson's Disease (PD), Resting-State functional MRI and 18 F-DOPA PET data, simultaneously acquired on a hybrid PET/MRI scanner, were retrospectively analyzed in 39 PD and 16 essential tremor patients. Correlations between posterior Putamen DOPA Uptake (pPDU) and the FC of the main CSTCL hubs were assessed separately in the two groups, analyzing the differences between the two groups by a group-by-pPDU interaction analysis of the resulting clusters' FC. Unlike in essential tremor, in PD patients pPDU correlated inversely with the FC of the thalamus with the sensorimotor cortices, and of the postcentral gyrus with the dorsal cerebellum, and directly with the FC of pre- and post-central gyri with both the superior and middle temporal gyri and the paracentral lobule, and of the caudate with the superior parietal cortex. The interaction analysis confirmed the significance of the difference between the two groups in these correlations. In PD patients, the post-central cortex FC, in the clusters correlating directly with pPDU, negatively correlated with both UPDRS motor examination score and Hoehn and Yahr stage, independent of the pPDU, suggesting that these FC changes contribute to motor impairment. In PD, nigrostriatal innervation loss correlates with a decrease in the FC within the sensorimotor network and between the sensorimotor network and the superior temporal cortices, possibly contributing to motor impairment, and with a strengthening of the thalamo-cortical FC, that may represent ineffective compensatory phenomena., (© 2022. The Author(s).)

Background and Objective: Relaxation parameter maps (RPMs) calculated from spin-echo data have provided a basis for the segmentation of normal brain tissues and white matter lesions in multiple sclerosis (MS) MRI studies. However, Conventional Spin-Echo (CSE) sequences, once the core of clinical MRI studies, have been largely replaced by faster ones, which do not allow the calculation a-posteriori of RPMs from clinical studies. Aim of the study was to develop and validate a method to estimate RPMs (pseudo-RPMs) from routine clinical MRI protocols (including 3D-Gradient Echo T1w, FLAIR and fast-T2w sequences), suitable for fully automatic multiparametric segmentation of normal-appearing and pathological brain tissues in MS., Methods: The proposed method processes spatially normalized clinical MRI studies through a multistep pipeline, to collect a set of data points of matched signal intensities (from MRI studies) and relaxation parameters (from a CSE-derived digital template and an MS lesion database), which are then fitted by a multiple and multivariate 4-th degree polynomial regression, providing pseudo-RPMs. The method was applied to a dataset of 59 clinical MRI studies providing pseudo-RPMs that were segmented through a method originally developed for the CSE-derived RPMs. Results of the segmentation in 12 studies were used to iteratively optimize method parameters. Accuracy of segmentation of normal-appearing brain tissues from the pseudo-RPMs was assessed by comparing their age-related changes, as measured in 47 clinical studies, against those measured acquired using CSE sequences in a comparable dataset of 47 patients. Lesion segmentation was validated against manual segmentation carried out by three neuroradiologists., Results: Age-related changes of normal-appearing brain tissue volumes measured using the pseudo-RPMs substantially overlapped those measured using the RPMs obtained from CSE sequences, and segmentation of MS lesions showed a moderate-high spatial overlap with manual segmentation, comparable to that achieved by the widely used Lesion Segmentation Tool on FLAIR images, with a greater volumetric agreement., Conclusions: The proposed approach allows calculation from clinical studies of pseudo-RPMs, which are equivalent to those obtainable from CSE sequences, avoiding the need for the acquisition of additional, dedicated sequences for segmentation purposes., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To stratify patients with multiple sclerosis (pwMS) based on brain MRI-derived volumetric features using unsupervised machine learning., Methods: The 3-T brain MRIs of relapsing-remitting pwMS including 3D-T1w and FLAIR-T2w sequences were retrospectively collected, along with Expanded Disability Status Scale (EDSS) scores and long-term (10 ± 2 years) clinical outcomes (EDSS, cognition, and progressive course). From the MRIs, volumes of demyelinating lesions and 116 atlas-defined gray matter regions were automatically segmented and expressed as z-scores referenced to external populations. Following feature selection, baseline MRI-derived biomarkers entered the Subtype and Stage Inference (SuStaIn) algorithm, which estimates subgroups characterized by distinct patterns of biomarker evolution and stages within subgroups. The trained model was then applied to longitudinal MRIs. Stability of subtypes and stage change over time were assessed via Krippendorf's α and multilevel linear regression models, respectively. The prognostic relevance of SuStaIn classification was assessed with ordinal/logistic regression analyses., Results: We selected 425 pwMS (35.9 ± 9.9 years; F/M: 301/124), corresponding to 1129 MRI scans, along with healthy controls (N = 148; 35.9 ± 13.0 years; F/M: 77/71) and external pwMS (N = 80; 40.4 ± 11.9 years; F/M: 56/24) as reference populations. Based on 11 biomarkers surviving feature selection, two subtypes were identified, designated as "deep gray matter (DGM)-first" subtype (N = 238) and "cortex-first" subtype (N = 187) according to the atrophy pattern. Subtypes were consistent over time (α = 0.806), with significant annual stage increase (b = 0.20; p < 0.001). EDSS was associated with stage and DGM-first subtype (p ≤ 0.02). Baseline stage predicted long-term disability, transition to progressive course, and cognitive impairment (p ≤ 0.03), with the latter also associated with DGM-first subtype (p = 0.005)., Conclusions: Unsupervised learning modelling of brain MRI-derived volumetric features provides a biologically reliable and prognostically meaningful stratification of pwMS., Key Points: • The unsupervised modelling of brain MRI-derived volumetric features can provide a single-visit stratification of multiple sclerosis patients. • The so-obtained classification tends to be consistent over time and captures disease-related brain damage progression, supporting the biological reliability of the model. • Baseline stratification predicts long-term clinical disability, cognition, and transition to secondary progressive course., (© 2022. The Author(s).)

Objective: The authors' objective was to measure the effect of posterior cranial vault distraction (PCVD) plus foramen magnum decompression (FMD) on dural sinus volume and venous flow in patients with syndromic craniosynostosis., Methods: The volumes of the sagittal, straight, transverse, and sigmoid sinuses of 5 consecutive patients with syndromic craniosynostosis who underwent PCVD+FMD were calculated in cubic centimeters with T2-weighted volumetric MRI sequences before surgery, immediately after surgery, and after the end of the distraction process. Tridimensional reconstructions of phase-contrast magnetic resonance angiography (PC-MRA) images were obtained with multiplanar reconstruction (MPR)., Results: The average total volume of all dural sinuses increased immediately after surgery (from 10.06 cm3 to 12.64 cm3) and continued to increase throughout the 30-day distraction period (from 12.64 cm3 to 14.71 cm3) (p = 0.04), except that the right sigmoid sinus remained stable after the initial increase. The most important increases were observed for the left transverse sinus (+113.2%), right transverse sinus (+104.3%), left sigmoid sinus (+91.3%), and sagittal sinus (+41.8%). Less important modifications were evident for the right sigmoid sinus (+33.7%) and straight sinus (+23.4%). Significant improvements in venous flow were noted on the tridimensional reconstructions of the PC-MRA images. Venous obstruction grading score improved in 4 patients (average [range] 2.4 [ 2-5]) (p = 0.023) and remained stable in 1 patient. All patients had chronic tonsillar herniation (CTH) (mean [range] 16.6 [8-26] mm), and 3 had syringomyelia. CTH showed improvement on the last follow-up MRI evaluation in 4 patients (mean [range] 10.5 [0-25] mm) and worsened from 15 mm to 19 mm in 1 patient. Syringomyelia improved in 2 patients and remained unchanged in 1., Conclusions: This study has provided the first radiological evidence of the impact of craniofacial surgery on dural sinus anatomy and venous drainage. The venous anomalies described in patients with syndromic craniosynostosis are not static, and PCVD+FMD triggers a dynamic process that can lead to significant modifications of intracranial venous drainage. The traction exerted by the distracted bone flap onto the occipitoparietal dura mater adherent to the inner calvaria may account for the enlargement of the dural sinus throughout the distraction period. The impact of these modifications on venous pressure, intracranial pressure, CTH, and hydrocephalus remains to be determined.

Whether chemotherapy (ChT) and radiotherapy (RT) determine neurocognitive impairment in acute lymphoblastic leukemia long-term survivors (ALL LTSs) through similar mechanisms affecting the same brain regions is still unknown. We compared neurocognitive alterations, regional brain tissue volumes (by voxel-based morphometry), and functional connectivity of the main default-mode network hubs (by seed-based analysis of resting state functional MRI data), in 13 ALL LTSs treated with RT and ChT (Group A) and 13 treated with ChT only (Group B). Group A performed significantly worse than Group B at the digit span and digit symbol tests ( p = 0.023 and 0.013, respectively). Increased connectivity between the medial prefrontal cortex (the main anterior hub of the default-mode network) and the rolandic operculi was present in Group A compared to Group B, along with the absence of significant differences in regional brain tissue volumes. In these regions, the functional connectivity correlated inversely with the speed of processing scores, independent of treatment group. These results suggest that similar mechanisms may be involved in the neurocognitive deficits in ALL LTS patients, regardless of the treatment group. Further studies are needed to clarify whether these changes represent a direct expression of the mechanisms underlying the cognitive deficits or ineffective compensatory phenomena.