Anderson-Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson\'s disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients\' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations.

Introduction: In the pediatric brain tumor surgery setting, intraoperative MRI (ioMRI) provides \"real-time\" imaging, allowing for evaluation of the extent of resection and detection of complications. The use of advanced MRI sequences could potentially provide additional physiological information that may aid in the preservation of healthy brain regions. This review aims to determine the added value of advanced imaging in ioMRI for pediatric brain tumor surgery compared to conventional imaging. Methods: Our systematic literature search identified relevant articles on PubMed using keywords associated with pediatrics, ioMRI, and brain tumors. The literature search was extended using the snowball technique to gather more information on advanced MRI techniques, their technical background, their use in adult ioMRI, and their use in routine pediatric brain tumor care. Results: The available literature was sparse and demonstrated that advanced sequences were used to reconstruct fibers to prevent damage to important structures, provide information on relative cerebral blood flow or abnormal metabolites, or to indicate the onset of hemorrhage or ischemic infarcts. The explorative literature search revealed developments within each advanced MRI field, such as multi-shell diffusion MRI, arterial spin labeling, and amide-proton transfer-weighted imaging, that have been studied in adult ioMRI but have not yet been applied in pediatrics. These techniques could have the potential to provide more accurate fiber tractography, information on intraoperative cerebral perfusion, and to match gadolinium-based T1w images without using a contrast agent. Conclusion: The potential added value of advanced MRI in the intraoperative setting for pediatric brain tumors is to prevent damage to important structures, to provide additional physiological or metabolic information, or to indicate the onset of postoperative changes. Current developments within various advanced ioMRI sequences are promising with regard to providing in-depth tissue information.

Spinal cord magnetic resonance imaging (MRI) has a central role in multiple sclerosis (MS) clinical practice for diagnosis and disease monitoring. Advanced MRI sequences capable of visualizing and quantifying tissue macro- and microstructure and reflecting different pathological disease processes have been used in MS research; however, the spinal cord remains under-explored, partly due to technical obstacles inherent to imaging this structure. We propose that the study of the spinal cord merits equal ambition in overcoming technical challenges, and that there is much information to be exploited to make valuable contributions to our understanding of MS. We present a narrative review on the latest progress in advanced spinal cord MRI in MS, covering in the first part structural, functional, metabolic and vascular imaging methods. We focus on recent studies of MS and those making significant technical steps, noting the challenges that remain to be addressed and what stands to be gained from such advances. Throughout we also refer to other works that presend more in-depth review on specific themes. In the second part, we present several topics that, in our view, hold particular potential. The need for better imaging of gray matter is discussed. We stress the importance of developing imaging beyond the cervical spinal cord, and explore the use of ultra-high field MRI. Finally, some recommendations are given for future research, from study design to newer developments in analysis, and the need for harmonization of sequences and methods within the field. This review is aimed at researchers and clinicians with an interest in gaining an overview of the current state of advanced MRI research in this field and what is primed to be the future of spinal cord imaging in MS research.

OBJECTIVE: This study aimed to evaluate the application of apparent diffusion coefficient (ADC) histogram analysis to differentiate posterior fossa tumors (PFTs) in children.
METHODS: A total of 175 pediatric patients with PFT, including 75 pilocytic astrocytomas (PA), 59 medulloblastomas, 16 ependymomas, and 13 atypical teratoid rhabdoid tumors (ATRT), were analyzed. Tumors were visually assessed using DWI trace and conventional MRI images and manually segmented and post-processed using parametric software (pMRI). Furthermore, tumor ADC values were normalized to the thalamus and cerebellar cortex. The following histogram metrics were obtained: entropy, minimum, 10th, and 90th percentiles, maximum, mean, median, skewness, and kurtosis to distinguish the different types of tumors. Kruskal Wallis and Mann-Whitney U tests were used to evaluate the differences. Finally, receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off values for differentiating the various PFTs.
RESULTS: Most ADC histogram metrics showed significant differences between PFTs (p < 0.001) except for entropy, skewness, and kurtosis. There were significant pairwise differences in ADC metrics for PA versus medulloblastoma, PA versus ependymoma, PA versus ATRT, medulloblastoma versus ependymoma, and ependymoma versus ATRT (all p < 0.05). Our results showed no significant differences between medulloblastoma and ATRT. Normalized ADC data showed similar results to the absolute ADC value analysis. ROC curve analysis for normalized ADCmedian values to thalamus showed 94.9% sensitivity (95% CI: 85-100%) and 93.3% specificity (95% CI: 87-100%) for differentiating medulloblastoma from ependymoma.
CONCLUSIONS: ADC histogram metrics can be applied to differentiate most types of posterior fossa tumors in children.

The shortly upcoming 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System is bringing extensive changes in the terminology of diffuse high-grade gliomas (DHGGs). Previously \"glioblastoma,\" as a descriptive entity, could have been applied to classify some tumors from the family of pediatric or adult DHGGs. However, now the term \"glioblastoma\" has been divested and is no longer applied to tumors in the family of pediatric types of DHGGs. As an entity, glioblastoma remains, however, in the family of adult types of diffuse gliomas under the insignia of \"glioblastoma, IDH-wildtype.\" Of note, glioblastomas still can be detected in children when glioblastoma, IDH-wildtype is found in this population, despite being much more common in adults. Despite the separation from the family of pediatric types of DHGGs, what was previously labeled as \"pediatric glioblastomas\" still remains with novel labels and as new entities. As a result of advances in molecular biology, most of the previously called \"pediatric glioblastomas\" are now classified in one of the four family members of pediatric types of DHGGs. In this review, the term glioblastoma is still apocryphally employed mainly due to its historical relevance and the paucity of recent literature dealing with the recently described new entities. Therefore, \"glioblastoma\" is used here as an umbrella term in the attempt to encompass multiple entities such as astrocytoma, IDH-mutant (grade 4); glioblastoma, IDH-wildtype; diffuse hemispheric glioma, H3 G34-mutant; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; and high grade infant-type hemispheric glioma. Glioblastomas are highly aggressive neoplasms. They may arise anywhere in the developing central nervous system, including the spinal cord. Signs and symptoms are non-specific, typically of short duration, and usually derived from increased intracranial pressure or seizure. Localized symptoms may also occur. The standard of care of \"pediatric glioblastomas\" is not well-established, typically composed of surgery with maximal safe tumor resection. Subsequent chemoradiation is recommended if the patient is older than 3 years. If younger than 3 years, surgery is followed by chemotherapy. In general, \"pediatric glioblastomas\" also have a poor prognosis despite surgery and adjuvant therapy. Magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of glioblastomas. In addition to the typical conventional MRI features, i.e., highly heterogeneous invasive masses with indistinct borders, mass effect on surrounding structures, and a variable degree of enhancement, the lesions may show restricted diffusion in the solid components, hemorrhage, and increased perfusion, reflecting increased vascularity and angiogenesis. In addition, magnetic resonance spectroscopy has proven helpful in pre- and postsurgical evaluation. Lastly, we will refer to new MRI techniques, which have already been applied in evaluating adult glioblastomas, with promising results, yet not widely utilized in children.

The accuracy of target delineation in radiation treatment (RT) planning of cerebral gliomas is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Conventional magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, represents the current standard imaging modality for target volume delineation of gliomas. However, conventional sequences have limited capability to discriminate treatment-related changes from viable tumors, owing to the low specificity of increased blood-brain barrier permeability and peritumoral edema. Advanced physiology-based MRI techniques, such as MR spectroscopy, diffusion MRI and perfusion MRI, have been developed for the biological characterization of gliomas and may circumvent these limitations, providing additional metabolic, structural, and hemodynamic information for treatment planning and monitoring. Radionuclide imaging techniques, such as positron emission tomography (PET) with amino acid radiopharmaceuticals, are also increasingly used in the workup of primary brain tumors, and their integration in RT planning is being evaluated in specialized centers. This review focuses on the basic principles and clinical results of advanced MRI and PET imaging techniques that have promise as a complement to RT planning of gliomas.

Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed.
We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test.
For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades.
The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.

This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET).
Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously. 18F-fluoroethyltyrosine (FET) PET improves the specificity of tumor diagnosis and evaluation of post-treatment changes. Incorporation of radiogenomics and machine learning methods further improve advanced imaging. The complementary nature of combining advanced imaging techniques across modalities for brain tumor imaging and incorporating technologies such as radiogenomics has the potential to reshape the landscape in neuro-oncology.

In recent years, the clinical assessment of primary brain tumors has been increasingly dependent on advanced magnetic resonance imaging (MRI) techniques in order to infer tumor pathophysiological characteristics, such as hemodynamics, metabolism, and microstructure. Quantitative radiomic data extracted from advanced MRI have risen as potential in vivo noninvasive biomarkers for predicting tumor grades and molecular subtypes, opening the era of \"molecular imaging\" and radiogenomics. This review presents the most relevant advancements in quantitative neuroimaging of advanced MRI techniques, by means of radiomics analysis, applied to primary brain tumors, including lower-grade glioma and glioblastoma, with a special focus on peculiar oncologic entities of current interest. Novel findings from diffusion MRI (dMRI), perfusion-weighted imaging (PWI), and MR spectroscopy (MRS) are hereby sifted in order to evaluate the role of quantitative imaging in neuro-oncology as a tool for predicting molecular profiles, stratifying prognosis, and characterizing tumor tissue microenvironments. Furthermore, innovative technological approaches are briefly addressed, including artificial intelligence contributions and ultra-high-field imaging new techniques. Lastly, after providing an overview of the advancements, we illustrate current clinical applications and future perspectives.

UNASSIGNED: There is an annual incidence of 50,000 glioma cases in Europe. The optimal treatment strategy is highly personalised, depending on tumour type, grade, spatial localization, and the degree of tissue infiltration. In research settings, advanced magnetic resonance imaging (MRI) has shown great promise as a tool to inform personalised treatment decisions. However, the use of advanced MRI in clinical practice remains scarce due to the downstream effects of siloed glioma imaging research with limited representation of MRI specialists in established consortia; and the associated lack of available tools and expertise in clinical settings. These shortcomings delay the translation of scientific breakthroughs into novel treatment strategy. As a response we have developed the network \"Glioma MR Imaging 2.0\" (GliMR) which we present in this article.
UNASSIGNED: GliMR aims to build a pan-European and multidisciplinary network of experts and accelerate the use of advanced MRI in glioma beyond the current \"state-of-the-art\" in glioma imaging. The Action Glioma MR Imaging 2.0 (GliMR) was granted funding by the European Cooperation in Science and Technology (COST) in June 2019.
UNASSIGNED: GliMR\'s first grant period ran from September 2019 to April 2020, during which several meetings were held and projects were initiated, such as reviewing the current knowledge on advanced MRI; developing a General Data Protection Regulation (GDPR) compliant consent form; and setting up the website.
UNASSIGNED: The Action overcomes the pre-existing limitations of glioma research and is funded until September 2023. New members will be accepted during its entire duration.