RANO 2.0 criteria: concepts applicable to the neuroradiologist's clinical practice.

PURPOSE OF REVIEW: The Response Assessment in Neuro-Oncology (RANO) 2.0 criteria aim at improving the standardization and reliability of treatment response assessment in clinical trials studying central nervous system (CNS) gliomas. This review presents the evidence supporting RANO 2.0 updates and discusses which concepts can be applicable to the clinical practice, particularly in the clinical radiographic reads. RECENT FINDINGS: Updates in RANO 2.0 were supported by recent retrospective analyses of multicenter data from recent clinical trials. As proposed in RANO 2.0, in tumors receiving radiation therapy, the post-RT MRI scan should be used as a reference baseline for the following scans, as opposed to the pre-RT scan, and radiographic findings suggesting progression within three months after radiation therapy completion should be verified with confirmatory scans. Volumetric assessments should be considered, when available, especially for low-grade gliomas, and the evaluation of nonenhancing disease should have a marginal role in glioblastoma. However, the radiographic reads in the clinical setting also benefit from aspects that lie outside RANO 2.0 criteria, such as qualitative evaluations, patient-specific clinical considerations, and advanced imaging. SUMMARY: While RANO 2.0 criteria are meant for the standardization of the response assessment in clinical trials, some concepts have the potential to improve patients' management in the clinical practice.

Optimizing Performance of Transformer-based Models for Fetal Brain MR Image Segmentation.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To test transformer-based models' performance when manipulating pretraining weights, dataset size, input size and comparing the best-model with reference standard and state-of-the-art models for a resting-state functional (rs-fMRI) fetal brain extraction task. Materials and Methods An internal retrospective dataset (fetuses = 172; images = 519; collected from 2018-2022) was used to investigate influence of dataset size, pretraining approaches and image input size on Swin-UNETR and UNETR models. The internal and an external (fetuses = 131; images = 561) datasets were used to cross-validate and to assess generalization capability of the best model against state-of-the-art models on different scanner types and number of gestational weeks (GW). The Dice similarity coefficient (DSC) and the Balanced average Hausdorff distance (BAHD) were used as segmentation performance metrics. GEE multifactorial models were used to assess significant model and interaction effects of interest. Results Swin-UNETR was not affected by pretraining approach and dataset size and performed best with the mean dataset image size, with a mean DSC of 0.92 and BAHD of 0.097. The Swin-UNETR was not affected by scanner type. Generalization results on the internal dataset showed that Swin-UNETR had lower performances compared with reference standard models and comparable performances on the external dataset. Cross-validation on internal and external test sets demonstrated better and comparable performance of Swin-UNETR versus convolutional neural network architectures during the late-fetal period (GWs > 25) but lower performance during the midfetal period (GWs ≤ 25). Conclusion Swin-UNTER showed flexibility in dealing with smaller datasets, regardless of pretraining approaches. For fetal brain extraction of rs-fMRI, Swin-UNTER showed comparable performance with reference standard models during the late-fetal period and lower performance during the early GW period. ©RSNA, 2024.

Neuromuscular imaging in clinical practice: an ESNR survey of 30 centers.

PURPOSE: We assessed the current clinical imaging practice in the primary evaluation of neuromuscular disorders (NMD), with respect to standardized imaging, evaluation and reporting through a European and extra-European-wide survey. METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) who had expressed their interest in NMD. The questionnaire featured 40 individual items. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication. RESULTS: A total of 30 unique entries from European and extra-European academic and non-academic institutions were received. Of these, 70% were neuroradiologists, 23% general radiologists and 7% musculoskeletal radiologists. Of the 30 responding institutes, 40% performed from 20 to 50 neuromuscular scans per year for suspected NMD. The principal modality used for a suspected myopathy was magnetic resonance imaging (MRI) (50%) or "mainly MRI" (47%). The primary imaging modality used for the evaluation of patients suspected of a neuropathy was MRI in 63% of all institutions and "mainly MRI" in 37%. For both muscle and nerve pathology, pelvic girdle and inferior limbs are the most scanned parts of the body (28%), followed by the thigh and leg (24%), whole body MR (24%), scapular girdle (16%), and the thigh in just 8% of institutions. Multiplanar acquisitions were performed in 50% of institutions. Convectional sequences used for muscle MRI included T2-STIR (88%), 2D T1weighted (w) (68%), T1 Dixon or equivalent (52%), T2 Dixon (40%), DWI (36%), 2D T2w (28%), T1 3D and T2 3D (20% respectively). For nerve MRI conventional sequences included T2-STIR (80%), DWI (56%), T2 3D (48%), 2D T2w (48%), T1 3D (44%), T1 Dixon or equivalent (44%), 2D T1 (36%), T2 Dixon (28%). Quantitative sequences were used regularly by 40% respondents. While only 28% of institutions utilized structured reports, a notable 88% of respondents expressed a desire for a standardized consensus structured report. Most of the respondents (93%) would be interested in a common MRI neuromuscular protocol and would like to be trained (87%) by the ESNR society with specific neuromuscular sessions in European annual meetings. CONCLUSIONS: Based on the survey findings, we can conclude that the current approach to neuromuscular imaging varies considerably among European and extra-European countries, both in terms of image acquisition and post-processing. Some of the challenges identified include the translation of research achievements (related to advanced imaging) into practical applications in a clinical setting, implementation of quantitative imaging post-processing techniques, adoption of structured reporting methods, and communication with referring physicians.

Meningioma and Other Meningeal Tumors.

Meningiomas develop from meningothelial cells and approximately account for more than 30 percent of central nervous system (CNS) tumors. They can occur anywhere in the dura, most often intracranially and at dural reflection sites. Half of the cases are usually at parasagittal/falcine and convexity locations; other common sites are sphenoid ridge, suprasellar, posterior fossa, and olfactory groove. The female-to-male ratio is approximately 2 or 3-1, and the median age at diagnosis is 65 years. Meningiomas are generally extremely slow-growing tumors; many are asymptomatic or paucisymptomatic at diagnosis and are discovered incidentally. Clinical manifestations, when present, are influenced by the tumor site and by the time course over which it develops. Meningiomas are divided into three grades. Grade I represents the vast majority of cases; they are considered typical or benign, although their CNS location can still lead to severe morbidity or mortality, resulting in a reported ten-year net survival of over 80%. Atypical (WHO grade II) meningiomas are considered "intermediate grade" malignancies and represent 5-7% of cases. They show a tendency for recurrence and malignant degeneration with a relevant increase in tumor cell migration and surrounding tissue infiltration; ten-year net survival is reported over 60%. The anaplastic subtype (WHO III) represents only 1-3% of cases, and it is characterized by a poor prognosis (ten-year net survival of 15%). The treatment of choice for these tumors stands on complete microsurgical resection in case the subsequent morbidities are assumed minimal. On the other hand, and in case the tumor is located in critical regions such as the skull base, or the patient may have accompanied comorbidities, or it is aimed to avoid intensive treatment, some other approaches, including stereotactic radiosurgery and radiotherapy, were recommended as safe and effective choices to be considered as a primary treatment option or complementary to surgery. Adjuvant radiosurgery/radiotherapy should be considered in the case of atypical and anaplastic histology, especially when a residual tumor is identifiable in postoperative imaging. A "watchful waiting" strategy appears reasonable for extremely old individuals and those with substantial comorbidities or low-performance status, while there is a reduced threshold for therapeutic intervention for relatively healthy younger individuals due to the expectation that tumor progression will inevitably necessitate proactive treatment. To treat and manage meningioma efficiently, the assessments of both neurosurgeons and radiation oncologists are essential. The possibility of other rarer tumors, including hemangiopericytomas, solitary fibrous tumors, lymphomas, metastases, melanocytic tumors, and fibrous histiocytoma, must be considered when a meningeal lesion is diagnosed, especially because the ideal diagnostic and therapeutic approaches might differ significantly in every tumor type.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

OBJECTIVES: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). METHODS: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. RESULTS: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. CONCLUSIONS: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. CLINICAL RELEVANCE STATEMENT: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. KEY POINTS: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Comprehensive Brain Tumour Characterisation with VERDICT-MRI: Evaluation of Cellular and Vascular Measures Validated by Histology.

The aim of this work was to extend the VERDICT-MRI framework for modelling brain tumours, enabling comprehensive characterisation of both intra- and peritumoural areas with a particular focus on cellular and vascular features. Diffusion MRI data were acquired with multiple b-values (ranging from 50 to 3500 s/mm2), diffusion times, and echo times in 21 patients with brain tumours of different types and with a wide range of cellular and vascular features. We fitted a selection of diffusion models that resulted from the combination of different types of intracellular, extracellular, and vascular compartments to the signal. We compared the models using criteria for parsimony while aiming at good characterisation of all of the key histological brain tumour components. Finally, we evaluated the parameters of the best-performing model in the differentiation of tumour histotypes, using ADC (Apparent Diffusion Coefficient) as a clinical standard reference, and compared them to histopathology and relevant perfusion MRI metrics. The best-performing model for VERDICT in brain tumours was a three-compartment model accounting for anisotropically hindered and isotropically restricted diffusion and isotropic pseudo-diffusion. VERDICT metrics were compatible with the histological appearance of low-grade gliomas and metastases and reflected differences found by histopathology between multiple biopsy samples within tumours. The comparison between histotypes showed that both the intracellular and vascular fractions tended to be higher in tumours with high cellularity (glioblastoma and metastasis), and quantitative analysis showed a trend toward higher values of the intracellular fraction (fic) within the tumour core with increasing glioma grade. We also observed a trend towards a higher free water fraction in vasogenic oedemas around metastases compared to infiltrative oedemas around glioblastomas and WHO 3 gliomas as well as the periphery of low-grade gliomas. In conclusion, we developed and evaluated a multi-compartment diffusion MRI model for brain tumours based on the VERDICT framework, which showed agreement between non-invasive microstructural estimates and histology and encouraging trends for the differentiation of tumour types and sub-regions.

Longitudinal brain functional connectivity changes induced by neurosurgical thalamotomy for tremor in Parkinson's disease: a preliminary study.

The hypothesis that the effectiveness of neurosurgical procedures in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of the stimulation and other brain regions is growing. This study aimed to assess resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in PD. A 76-year-old right-handed woman with refractory tremor-dominant PD was selected as a candidate for left Vim radiosurgery thalamotomy. Clinical and motion sensor evaluation and brain resting-state functional MRI (rs-fMRI) were carried out before treatment and 3, 6, and 12 months later. Targeted Vim was selected as region of interest and a seed-based rs-fMRI analysis was performed in the patient and ten age- and sex-matched controls at baseline and over time. Furthermore, a correlation analysis between functional connectivity and tremor data was carried out. Both clinical and motion sensor measurements showed a progressive tremor improvement over time on right side after radiosurgery. In the patient, seed-based analysis showed a significantly increased functional connectivity between targeted Vim and ipsilateral visual areas relative to controls before treatment. Over 1 year, a normalization of aberrant pre-therapeutic functional connectivity between Vim and visual areas was obtained. At correlation analysis, the reduction of tremor metrics over time, assessed by clinical evaluation and wearable motion sensors, was related to the reduction of the left Vim-left visual cortex functional connectivity. Our findings support the evidence that fMRI was able to detect targeted Vim connectivity and its changes over time after thalamotomy.

Combining semi-quantitative rating and automated brain volumetry in MRI evaluation of patients with probable behavioural variant of fronto-temporal dementia: an added value for clinical practise?

PURPOSE: To evaluate the diagnostic value of combined semiquantitative and quantitative assessment of brain atrophy in the diagnostic workup of the behavioural-variant of frontotemporal dementia (bvFTD). METHODS: Three neuroradiologists defined brain atrophy grading and identified atrophy pattern suggestive of bvFTD on 3D-T1 brain MRI of 112 subjects using a semiquantitative rating scale (Kipps'). A quantitative atrophy assessment was performed using two different automated software (Quantib® ND and Icometrix®). A combined semiquantitative and quantitative assessment of brain atrophy was made to evaluate the improvement in brain atrophy grading to identify probable bvFTD patients. RESULTS: Observers' performances in the diagnosis of bvFTD were very good for Observer 1 (k value = 0.881) and 2 (k value = 0.867), substantial for Observer 3 (k value = 0.741). Semiquantitative atrophy grading of all the observers showed a moderate and a poor correlation with the volume values calculated by Icometrix® and by Quantib® ND, respectively. For the definition of neuroradiological signs presumptive of bvFTD, the use of Icometrix® software improved the diagnostic accuracy for Observer 1 resulting in an AUC of 0.974, and for Observer 3 resulting in a AUC of 0.971 (p-value < 0.001). The use of Quantib® ND software improved the diagnostic accuracy for Observer 1 resulting in an AUC of 0.974, and for Observer 3 resulting in a AUC of 0.977 (p-value < 0.001). No improvement was observed for Observer 2. CONCLUSION: Combining semiquantitative and quantitative brain imaging evaluation allows to reduce discrepancies in the neuroradiological diagnostic workup of bvFTD by different readers.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Imaging characterization of an adult H3 K27M-altered diffuse midline glioma of the medulla oblongata with a confounding steroid response.

We report an uncommon, infratentorial localization of adult H3 K27M-altered diffuse midline glioma arising in a particularly rare site (medulla oblongata). In addition to this unusual presentation, the lesion exhibited a substantial contrast enhancement and size decrease after dexamethasone, generating diagnostic dilemmas. Histology, molecular details, advanced Magnetic Resonance imaging features and differential diagnoses are here described and discussed, as well as common misconceptions about steroid-sensitive mass lesions, and practical difficulties for clinicians involved in the process of making diagnosis.

Evaluating syntactic comprehension during awake intraoperative cortical stimulation mapping.

OBJECTIVE: Electrocortical stimulation mapping (ECS) is widely used to identify essential language areas, but sentence-level processing has rarely been investigated. METHODS: While undergoing awake surgery in the dominant left hemisphere, 6 subjects were asked to comprehend sentences varying in their demands on syntactic processing. RESULTS: In all 6 subjects, stimulation of the inferior frontal gyrus disrupted comprehension of passive sentences, which critically depend on syntactic processing to correctly assign grammatical roles, without disrupting comprehension of simpler tasks. In 4 of the 6 subjects, these sites were localized to the pars opercularis. Sentence comprehension was also disrupted by stimulation of other perisylvian sites, but in a more variable manner. CONCLUSIONS: These findings suggest that there may be language regions that differentially contribute to sentence processing and which therefore are best identified using sentence-level tasks. The functional consequences of resecting these sites remain to be investigated.

Aberrant L-Fucose Accumulation and Increased Core Fucosylation Are Metabolic Liabilities in Mesenchymal Glioblastoma.

Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome, and the glycoproteome of human subgroup-specific GBM sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated that most MES-restricted core-fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion, and integrin-mediated signaling. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets. SIGNIFICANCE: Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.

Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study.

Background: Tumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging. Objectives: This study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity. Materials and Methods: Seventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats' spatial distribution, quantitative features and histopathological characteristics were analyzed. Results: A highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed. Conclusion: Preliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.

RS-FetMRI: a MATLAB-SPM Based Tool for Pre-processing Fetal Resting-State fMRI Data.

Resting-state functional magnetic resonance imaging (rs-fMRI) most recently has proved to open a measureless window on functional neurodevelopment in utero. Fetal brain activation and connectivity maps can be heavily influenced by 1) fetal-specific motion effects on the time-series and 2) the accuracy of time-series spatial normalization to a standardized gestational-week (GW) specific fetal template space.Due to the absence of a standardized and generalizable image processing protocol, the objective of the present work was to implement a validated fetal rs-fMRI preprocessing pipeline (RS-FetMRI) divided into 6 inter-dependent preprocessing modules (i.e., M1 to M6) and designed to work entirely as an extension for Statistical Parametric Mapping (SPM).RS-FetMRI pipeline output analyses on rs-fMRI time-series sampled from a cohort of fetuses acquired on both 1.5 T and 3 T MRI scanning systems showed increased efficacy of estimation of the degree of movement coupled with an efficient motion censoring procedure, resulting in increased number of motion-uncorrupted volumes and temporal continuity in fetal rs-fMRI time-series data. Moreover, a "structural-free" SPM-based spatial normalization procedure granted a high degree of spatial overlap with high reproducibility and a significant improvement in whole-brain and parcellation-specific Temporal Signal-to-Noise Ratio (TSNR) mirrored by functional connectivity analysis.To our knowledge, the RS-FetMRI pipeline is the first semi-automatic and easy-to-use standardized fetal rs-fMRI preprocessing pipeline completely integrated in MATLAB-SPM able to remove entry barriers for new research groups into the field of fetal rs-fMRI, for both research or clinical purposes, and ultimately to make future fetal brain connectivity investigations more suitable for comparison and cross-validation.

Comparison between inferior frontal gyrus intrinsic connectivity network and verb-generation task fMRI network for presurgical language mapping in healthy controls and in glioma patients.

Task-based functional MRI (tb-fMRI) represents an extremely valuable approach for the identification of language eloquent regions for presurgical mapping in patients with brain tumors. However, its routinely application is limited by patient-related factors, such as cognitive disability and difficulty in coping with long-time acquisitions, and by technical factors, such as lack of equipment availability for stimuli delivery. Resting-state fMRI (rs-fMRI) instead, allows the identification of distinct language networks in a 10-min acquisition without the need of performing active tasks and using specific equipment. Therefore, to test the feasibility of rs-fMRI as a preoperative mapping tool, we reconstructed a lexico-semantic intrinsic connectivity network (ICN) in healthy controls (HC) and in a case series of patients with gliomas and compared the organization of this language network with the one derived from tb-fMRI in the patient's group. We studied three patients with extra-frontal gliomas who underwent functional mapping with auditory verb-generation (AVG) task and rs-fMRI with a seed in the left inferior frontal gyrus (IFG). First, we identified the functional connected areas to the IFG in HC. We qualitatively compared these areas with those that showed functional activation in AVG task derived from Neurosynth meta-analysis. Last, in each patient we performed single-subject analyses both for rs- and tb-fMRI, and we evaluated the spatial overlap between the two approaches. In HC, the IFG-ICN network showed a predominant left fronto-temporal functional connectivity in regions overlapping with the AVG network derived from a meta-analysis. In two patients, rs- and tb-fMRI showed comparable patterns of activation in left fronto-temporal regions, with different levels of contralateral activations. The third patient could not accomplish the AVG task and thus it was not possible to make any comparison with the ICN. However, in this patient, task-free approach disclosed a consistent network of fronto-temporal regions as in HC, and additional parietal regions. Our preliminary findings support the value of rs-fMRI approach for presurgical mapping, particularly for identifying left fronto-temporal core language-related areas in glioma patients. In a preoperative setting, rs-fMRI approach could represent a powerful tool for the identification of eloquent language areas, especially in patients with language or cognitive impairments.

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network.

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures.

Aftereffects to Prism Exposure without Adaptation: A Single Case Study.

Visuo-motor adaptation to optical prisms (Prism Adaptation, PA), displacing the visual scene laterally, is a behavioral method used for the experimental investigation of visuomotor plasticity, and, in clinical settings, for temporarily ameliorating and rehabilitating unilateral spatial neglect. This study investigated the building up of PA, and the presence of the typically occurring subsequent Aftereffects (AEs) in a brain-damaged patient (TMA), suffering from apperceptive agnosia and a right visual half-field defect, with bilateral atrophy of the parieto-occipital cortices, regions involved in PA and AEs. Base-Right prisms and control neutral lenses were used. PA was achieved by repeated pointing movements toward three types of stimuli: visual, auditory, and bimodal audio-visual. The presence and the magnitude of AEs were assessed by proprioceptive, visual, visuo-proprioceptive, and auditory-proprioceptive straight-ahead pointing tasks. The patient's brain connectivity was investigated by Diffusion Tensor Imaging (DTI). Unlike control participants, TMA did not show any adaptation to prism exposure, but her AEs were largely preserved. These findings indicate that AEs may occur even in the absence of PA, as indexed by the reduction of the pointing error, showing a dissociation between the classical measures of PA and AEs. In the PA process, error reduction, and its feedback, may be less central to the building up of AEs, than the sensorimotor pointing activity per se.

Morphometric study of the ventricular indexes in healthy ovine BRAIN using MRI.

BACKGROUND: Sheep (Ovis aries) have been largely used as animal models in a multitude of specialties in biomedical research. The similarity to human brain anatomy in terms of brain size, skull features, and gyrification index, gives to ovine as a large animal model a better translational value than small animal models in neuroscience. Despite this evidence and the availability of advanced imaging techniques, morphometric brain studies are lacking. We herein present the morphometric ovine brain indexes and anatomical measures developed by two observers in a double-blinded study and validated via an intra- and inter-observer analysis. RESULTS: For this retrospective study, T1-weighted Magnetic Resonance Imaging (MRI) scans were performed at 1.5 T on 15 sheep, under general anaesthesia. The animals were female Ovis aries, in the age of 18-24 months. Two observers assessed the scans, twice time each. The statistical analysis of intra-observer and inter-observer agreement was obtained via the Bland-Altman plot and Spearman rank correlation test. The results are as follows (mean ± Standard deviation): Indexes: Bifrontal 0,338 ± 0,032 cm; Bicaudate 0,080 ± 0,012 cm; Evans' 0,218 ± 0,035 cm; Ventricular 0,241 ± 0,039 cm; Huckman 1693 ± 0,174 cm; Cella Media 0,096 ± 0,037 cm; Third ventricle ratio 0,040 ± 0,007 cm. Anatomical measures: Fourth ventricle length 0,295 ± 0,073 cm; Fourth ventricle width 0,344 ± 0,074 cm; Left lateral ventricle 4175 ± 0,275 cm; Right lateral ventricle 4182 ± 0,269 cm; Frontal horn length 1795 ± 0,303 cm; Interventricular foramen left 1794 ± 0,301 cm; Interventricular foramen right 1,78 ± 0,317 cm. CONCLUSIONS: The present study provides baseline values of linear indexes of the ventricles in the ovine models. The acquisition of these data contributes to filling the knowledge void on important anatomical and morphological features of the sheep brain.

Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities.

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain.