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Objective: To provide quantitative magnetic resonance imaging (MRI) super‐resolution‐based three‐dimensional volumetric reference data on the growth dynamics of the ganglionic eminence (GE) relative to cortical and total fetal brain volumes (TBV). Methods: This was a retrospective study of fetuses without structural central nervous system anomalies or other confounding comorbidities that were referred for fetal MRI. Super‐resolution reconstructions of 1.5‐ and 3‐Tesla T2‐weighted images were generated. Semiautomatic segmentation of TBV and cortical volume and manual segmentation of the GE were performed. Cortical volume, TBV and GE volume were quantified and three‐dimensional reconstructions were generated to visualize the developmental dynamics of the GE. Results: Overall, 120 fetuses that underwent 127 MRI scans at a mean gestational age of 27.23 ± 4.81 weeks (range, 20–37 weeks) were included. In the investigated gestational‐age range, GE volume ranged from 74.88 to 808.75 mm3 and was at its maximum at 21 gestational weeks, followed by a linear decrease (R2 = 0.559) throughout the late second and third trimesters. A pronounced reduction in GE volume relative to cortical volume and TBV occurred in the late second trimester, with a decline in this reduction observed in the third trimester (R2 = 0.936 and 0.924, respectively). Three‐dimensional rendering allowed visualization of a continuous change in the shape and size of the GE throughout the second and third trimesters. Conclusions: Even small compartments of the fetal brain, which are not easily accessible by standardized two‐dimensional modalities, can be assessed precisely by super‐resolution processed fetal MRI. The inverse growth dynamics of GE volume compared with TBV and cortical volume reflects the transitory nature and physiological involution of this (patho‐)physiologically important brain structure. The normal development and involution of the GE is mandatory for normal cortical development. Pathological changes of this transient organ precede impairment of cortical structures, and their detection may allow an earlier diagnosis of such anomalies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Biallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency., Methods: Nine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing., Results: We identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals., Conclusions: Our data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed., Materials and Methods: In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities., Results: Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [ r = -0.459; P  = .021]; midbrain [ r = -0.413; P  = .040]), T2-relaxation times (medulla oblongata [ r = -0.625; P  < .001]; midbrain [ r = -0.571; P  = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [ r = -0.433; P  = .035]; midbrain [ r = -0.386; P  = .062]), and T2-relaxation times (medulla oblongata [ r =-0.883; P  < .001]; midbrain [ r = -0.890; P  < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain)., Conclusions: There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development., (© 2024 by American Journal of Neuroradiology.)

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel review is written with the central aim of providing an easy-to-understand roadmap to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. The utility of each available neuroimaging modality including prenatal multiplanar neurosonography, anatomical magnetic resonance imaging (MRI), and advanced MRI techniques, as well as further insights from post-mortem imaging have been highlighted for every developmental stage., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: This study aimed to assess the visibility of the indusium griseum (IG) in magnetic resonance (MR) scans of the human fetal brain and to evaluate its reliability as an imaging biomarker of the normality of brain midline development., Material and Methods: The retrospective observational study encompassed T2-w 3T MR images from 90 post-mortem fetal brains and immunohistochemical sections from 41 fetal brains (16-40 gestational weeks) without cerebral pathology. Three raters independently inspected and evaluated the visibility of IG in post-mortem and in vivo MR scans. Weighted kappa statistics and regression analysis were used to determine inter- and intra-rater agreement and the type and strength of the association of IG visibility with gestational age., Results: The visibility of the IG was the highest between the 25 and 30 gestational week period, with a very good inter-rater variability (kappa 0.623-0.709) and excellent intra-rater variability (kappa 0.81-0.93). The immunochemical analysis of the histoarchitecture of IG discloses the expression of highly hydrated extracellular molecules in IG as the substrate of higher signal intensity and best visibility of IG during the mid-fetal period., Conclusions: The knowledge of developmental brain histology and fetal age allows us to predict the IG-visibility in magnetic resonance imaging (MRI) and use it as a biomarker to evaluate the morphogenesis of the brain midline. As a biomarker, IG is significant for post-mortem pathological examination by MRI. Therefore, in the clinical in vivo imaging examination, IG should be anticipated when an assessment of the brain midline structures is needed in mid-gestation, including corpus callosum thickness measurements., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Deep learning models for medical image segmentation can fail unexpectedly and spectacularly for pathological cases and images acquired at different centers than training images, with labeling errors that violate expert knowledge. Such errors undermine the trustworthiness of deep learning models for medical image segmentation. Mechanisms for detecting and correcting such failures are essential for safely translating this technology into clinics and are likely to be a requirement of future regulations on artificial intelligence (AI). In this work, we propose a trustworthy AI theoretical framework and a practical system that can augment any backbone AI system using a fallback method and a fail-safe mechanism based on Dempster-Shafer theory. Our approach relies on an actionable definition of trustworthy AI. Our method automatically discards the voxel-level labeling predicted by the backbone AI that violate expert knowledge and relies on a fallback for those voxels. We demonstrate the effectiveness of the proposed trustworthy AI approach on the largest reported annotated dataset of fetal MRI consisting of 540 manually annotated fetal brain 3D T2w MRIs from 13 centers. Our trustworthy AI method improves the robustness of four backbone AI models for fetal brain MRIs acquired across various centers and for fetuses with various brain abnormalities.

Purpose: To evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective., Methods: One hundred and eight neuropediatric patients (54 male, 54 female, 0-17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The NDP and GPT ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient's age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths., Results: The inter-reader agreement was good for GPT and NDP in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in GPT (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions., Conclusion: Measurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Malformations of cortical development (MCD) can frequently be diagnosed at multi-disciplinary Fetal Neurology clinics with the aid of multiplanar neurosonography and MRI. The patients are usually referred following prenatal sonographic screening that raises the suspicion of a possible underlying MCD. These indirect findings include, but are not limited to, ventriculomegaly (lateral ventricles larger than 10 mm), asymmetric ventricles, commissural anomalies, absent cavum septum pellucidum, cerebellar vermian and/or hemispheric anomalies, abnormal head circumference (microcephaly or macrocephaly), multiple CNS malformations, and associated systemic defects. The aim of this paper is to suggest a practical approach to prenatal diagnosis of malformations of cortical development utilizing dedicated neurosonography and MRI, based on the current literature and our own experience. We suggest that an MCD should be suspected in utero when the following intracranial imaging signs are present: abnormal development of the Sylvian fissure; delayed achievement of cortical milestones, premature appearance of sulcation; irregular ventricular borders, abnormal cortical thickness (thick, thin); abnormal shape and orientation of the sulci and gyri; irregular, abnormal, asymmetric, and enlarged hemisphere; simplified cortex; non continuous cortex or cleft; and intraparenchymal echogenic nodules. Following the putative diagnosis of fetal MCD by neurosonography and MRI, when appropriate and possible (depending on gestational age), the imaging diagnosis is supplemented by genetic studies (CMA and trio whole exome sequencing). In some instances, no further studies are required during pregnancy due to the clear dire prognosis and then the genetic evaluation can be deferred after delivery or termination of pregnancy (in countries where allowed)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk.

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

The subplate (SP) is a transient structure of the human fetal brain that becomes the most prominent layer of the developing pallium during the late second trimester. It is important in the formation of thalamocortical and cortico-cortical connections. The SP is vulnerable in perinatal brain injury and may play a role in complex neurodevelopmental disorders, such as schizophrenia and autism. Nine postmortem fetal human brains (19-24 GW) were imaged on a 3 Tesla MR scanner and the T2-w images in the frontal and temporal lobes were compared, in each case, with the histological slices of the same brain. The brains were confirmed to be without any brain pathology. The purpose of this study was to demonstrate that the superficial SP (sSP) and deep SP (dSP) can be discriminated on postmortem MR images. More specifically, we aimed to clarify that the observable, thin, hyperintense layer below the cortical plate in the upper SP portion on T2-weighted MR images has an anatomical correspondence to the histologically established sSP. Therefore, the distinction between the sSP and dSP layers, using clinically available MR imaging methodology, is possible in postmortem MRI and can help in the imaging interpretation of the fetal cerebral layers., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The periventricular crossroads have been described as transient structures of the fetal brain where major systems of developing fibers intersect. The triangular parietal crossroad constitutes one major crossroad region. By combining in vivo and post-mortem fetal MRI with histological and immunohistochemical methods, we aimed to characterize these structures. Data from 529 in vivo and 66 post-mortem MRI examinations of fetal brains between gestational weeks (GW) 18-39 were retrospectively reviewed. In each fetus, the area adjacent to the trigone of the lateral ventricles at the exit of the posterior limb of the internal capsule (PLIC) was assessed with respect to signal intensity, size, and shape on T2-weighted images. In addition, by using in vivo diffusion tensor imaging (DTI), the main fiber pathways that intersect in these areas were identified. In order to explain the in vivo features of the parietal crossroads (signal intensity and developmental profile), we analyzed 23 post-mortem fetal human brains, between 16 and ​40 GW of age, processed by histological and immunohistochemical methods. The parietal crossroads were triangular-shaped areas with the base in the continuity of the PLIC, adjacent to the germinal matrix and the trigone of the lateral ventricles, with the tip pointing toward the subplate. These areas appeared hyperintense to the subplate, and corresponded to a convergence zone of the developing external capsule, the PLIC, and the fronto-occipital association fibers. They were best detected between GW 25-26, and, at term, they became isointense to the adjacent structures. The immunohistochemical results showed a distinct cellular, fibrillar, and extracellular matrix arrangement in the parietal crossroads, depending on the stage of development, which influenced the MRI features. The parietal crossroads are transient, but important structures in white matter maturation and their damage may be indicative of a poor prognosis for a fetus with regard to neurological development. In addition, impairment of this region may explain the complex neurodevelopmental deficits in preterm infants with periventricular hypoxic/ischemic or inflammatory lesions., Competing Interests: Declaration of competing interest The authors of this manuscript declare that they do not any financial or academic conflict of interest associated with the submitted manuscript., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Disorders of migration and gyration are a versatile group of pathologies that may cause epilepsy and/or neurodevelopmental delay. With the recent improvement of imaging methods, it is possible to detect these pathologies, not only on postnatal MRI but also in utero using fetal MRI. The use of MRI together with genetic tests and knowledge of the classification of these malformations makes early diagnosis possible. Furthermore, the exact diagnosis of disorders of gyration and migration will help ensure better treatment of symptomatic epilepsies as well as be of great help in counselling the parents if detected in utero. Ultimately, it may enable the development of new treatment strategies. Therefore, in this review the fetal neuroanatomy and pathologies due to migration and abnormal postmigratory processes together with the recent classification of these malformations are elucidated, which will ensure early diagnosis of these types of developmental disorders.

The recent technological advancement of fast magnetic resonance imaging (MRI) sequences allowed the inclusion of diffusion tensor imaging, functional MRI, and proton MR spectroscopy in prenatal imaging protocols. These methods provide information beyond morphology and hold the key to improving several fields of human neuroscience and clinical diagnostics. Our review introduces the fundamental works that enabled these imaging techniques, and also highlights the most recent contributions to this emerging field of prenatal diagnostics, such as the structural and functional connectomic approach. We introduce the advanced image processing approaches that are extensively used to tackle fetal or maternal movement-related image artifacts, and which are necessary for the optimal interpretation of such imaging data., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical subplate zone. We studied the cortical wall of noncystic and cystic PWMI cases and controls. Non-cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post-mortem human frontal lobes from very preterm [24–29 postconceptional weeks (pcw)] and preterm infants (30–34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1(MCT1), ionized calcium-binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the subplate in non-cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age-related and laminar differences were observed in non-cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the subplate but throughout the cortical plate. There were no differences in Olig2-positive pre-oligodendrocytes in the subplate inPWMI cases compared with controls. The involvement of gliosis in the deep subplate supports the concept of the complex cellular vulnerability of the subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI., (© 2013 International Society of Neuropathology.)

Acquired central nervous system (CNS) lesions are often subtle; therefore, the prenatal diagnosis of these lesions is extremely important. The fetal ultrasound examination and magnetic resonance imaging (MRI) are two important imaging methods that give an insight into these types lesions. The method of choice during pregnancy is still fetal ultrasound; however, fetal MRI is important when there are certain pathologies, e.g. periventricular leukomalacia (PVL) or malformations of the vein of Galen. In this manner clinicians can plan further therapy after childbirth in advance (e.g. cerebral angiography or embolization).

Disabilities after brain injury in very preterm infants have mainly been attributed to noncystic periventricular white matter injury (PWMI). We analyzed spatiotemporal patterns of PWMI in the brains of 18 very preterm infants (25-29 postconceptional weeks [pcw]), 7 preterm infants (30-34 pcw), and 10 preterm controls without PWMI. In very preterm infants, we examined PWMI in detail in 2 axonal crossroad areas in the frontal lobe: C1 (lateral to the lateral angle of the anterior horn of the lateral ventricle, at the exit of the internal capsule radiations) and C2 (above the corpus callosum and dorsal angle of the anterior horn). These brains had greater microglia-macrophage densities and activation but lesser astroglial reaction (glial fibrillary acidic protein and monocarboxylate transporter 1 expression) than in preterm cases with PWMI. In preterm infants, scattered necrotic foci were rimmed by axonal spheroids and ionized calcium binding adaptor molecule 1-positive macrophages. Diffuse lesions near these foci consisted primarily of hypertrophic and reactive astrocytes associated with fewer microglia. No differences in Olig2-positive preoligodendrocytes between noncystic PWMI and control cases were found. These data show that the growing axonal crossroad areas are highly vulnerable to PWMI in very preterm infants and highlight differences in glial activation patterns between very preterm and preterm infants.