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Abstract Arterial spin labeling (ASL) is increasingly applied for cerebral blood flow mapping, but $${\\text{T}}_{{2}}$$ T 2 relaxation of the ASL signal magnetization is often ignored, although it may be clinically relevant. To investigate the extent, to which quantitative $${\\text{T}}_{{2}}$$ T 2 values in gray matter (GM) obtained by pseudocontinuous ASL (pCASL) perfusion MRI can be reproduced, are reliable and a potential neuroscientific biomarker, a prospective study was performed with ten healthy volunteers (5F,28 ± 3y) at a 3 T scanner. A $${\\text{T}}_{{2}}$$ T 2 -prepared pCASL sequence enabled the measurement of quantitative $${\\text{T}}_{{2}}$$ T 2 and perfusion maps. $${\\text{T}}_{{2}}$$ T 2 times were modeled per voxel and analyzed within four GM-regions-of-interest (ROI). The intraclass correlation coefficients (ICCs) of the quantified ASL- $${\\text{T}}_{{2}}$$ T 2 varied across brain regions. When averaged across subjects and postlabeling delays (PLDs), the ICCs ranged from reasonable values in parietal regions (ICC = 0.56) to smaller values in frontal regions (ICC = 0.36). Corresponding subject-averaged within-subject coefficients of variation (WSCVs) showed good test–retest measurement precision ( $${\\text{WSCV}}_{{{\\text{PLD}}} \\le 0.14$$ WSCV PLD ≤ 0.14 for all PLDs), but more pronounced inter-subject variance. Reliability and precision of quantified ASL- $${\\text{T}}_{{2}}$$ T 2 were region-, PLD- and subject-specific, showing fair to robust results in occipital, parietal and temporal ROIs. The results give rise to consider the method for future cerebral studies, where variable perfusion or altered $${\\text{T}}_{{2}}$$ T 2 times are suspected.

The perfusion parameters cerebral blood flow (CBF) and arterial transit time (ATT) measured with arterial spin labeling (ASL) magnetic resonance imaging (MRI) provide valuable essentials to assess the integrity of cerebral tissue. Brain perfusion changes, due to aging, an intervention, or neurodegenerative diseases for example, could be investigated in longitudinal ASL studies with reliable ASL sequences. Generally, pseudo-continuous ASL (pCASL) is preferred because of its larger signal-to-noise ratio (SNR) compared to pulsed ASL (PASL) techniques. Available pCASL versions differ regarding their feature details. To date only little is known about the reliability and reproducibility of CBF and ATT measures obtained with the innovative Hadamard encoded pCASL variant, especially if applied on participants in old age. Therefore, we investigated an in-house developed Hadamard encoded pCASL sequence on a group of healthy elderly at two different 3 Tesla Siemens MRI systems (Skyra and mMR Biograph) and evaluated CBF and ATT reliability and reproducibility for several regions-of-interests (ROI). Calculated within-subject coefficients of variation (wsCV) demonstrated an excellent reliability of perfusion measures, whereas ATT appeared to be even more reliable than CBF [e.g., wsCV(CBF) = 2.9% vs. wsCV(ATT) = 2.3% for a gray matter (GM) ROI on Skyra system]. Additionally, a substantial agreement of perfusion values acquired on both MRI systems with an inter-session interval of 78 ± 17.6 days was shown by high corresponding intra-class correlation (ICC) coefficients [e.g., ICC(CBF) = 0.704 and ICC(ATT) = 0.754 for a GM ROI]. The usability of this novel Hadamard encoded pCASL sequence might improve future follow-up perfusion studies of the aging and/or diseased brain.

Automated detection of lesions using artificial intelligence creates new standards in medical imaging. For people with epilepsy, automated detection of focal cortical dysplasias (FCDs) is widely used because subtle FCDs often escape conventional neuroradiological diagnosis. Accurate recognition of FCDs, however, is of outstanding importance for affected people, as surgical resection of the dysplastic cortex is associated with a high chance of postsurgical seizure freedom. Here, we make publicly available a dataset of 85 people affected by epilepsy due to FCD type II and 85 healthy control persons. We publish 3D-T1 and 3D-FLAIR, manually labeled regions of interest, and carefully selected clinical features. The open presurgery MRI dataset may be used to validate existing automated algorithms of FCD detection as well as to create new approaches. Most importantly, it will enable comparability of already existing approaches and support a more widespread use of automated lesion detection tools.

Neuronal dysfunction due to iron accumulation in conjunction with reactive oxygen species (ROS) could represent an important, yet underappreciated, component of the epileptogenic process. However, to date, alterations in iron metabolism in the epileptogenic brain have not been addressed in detail. Iron-related neuropathology and antioxidant metabolic processes were investigated in resected brain tissue from patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), post-mortem brain tissue from patients who died after status epilepticus (SE) as well as brain tissue from the electrically induced SE rat model of TLE. Magnetic susceptibility of the presumed seizure-onset zone from three patients with focal epilepsy was compared during and after seizure activity. Finally, the cellular effects of iron overload were studied in vitro using an acute mouse hippocampal slice preparation and cultured human fetal astrocytes. While iron-accumulating neurons had a pyknotic morphology, astrocytes appeared to acquire iron-sequestrating capacity as indicated by prominent ferritin expression and iron retention in the hippocampus of patients with SE or TLE. Interictal to postictal comparison revealed increased magnetic susceptibility in the seizure-onset zone of epilepsy patients. Post-SE rats had consistently higher hippocampal iron levels during the acute and chronic phase (when spontaneous recurrent seizures are evident). In vitro, in acute slices that were exposed to iron, neurons readily took up iron, which was exacerbated by induced epileptiform activity. Human astrocyte cultures challenged with iron and ROS increased their antioxidant and iron-binding capacity, but simultaneously developed a pro-inflammatory phenotype upon chronic exposure. These data suggest that seizure-mediated, chronic neuronal iron uptake might play a role in neuronal dysfunction/loss in TLE-HS. On the other hand, astrocytes sequester iron, specifically in chronic epilepsy. This function might transform astrocytes into a highly resistant, pro-inflammatory phenotype potentially contributing to pro-epileptogenic inflammatory processes.

Arterial spin labeling (ASL) is increasingly applied for cerebral blood flow mapping, but$${\\text{T}}_{{2}}$$T 2 relaxation of the ASL signal magnetization is often ignored, although it may be clinically relevant. To investigate the extent, to which quantitative$${\\text{T}}_{{2}}$$T 2 values in gray matter (GM) obtained by pseudocontinuous ASL (pCASL) perfusion MRI can be reproduced, are reliable and a potential neuroscientific biomarker, a prospective study was performed with ten healthy volunteers (5F,28 ± 3y) at a 3 T scanner. A$${\\text{T}}_{{2}}$$T 2 -prepared pCASL sequence enabled the measurement of quantitative$${\\text{T}}_{{2}}$$T 2 and perfusion maps.$${\\text{T}}_{{2}}$$T 2 times were modeled per voxel and analyzed within four GM-regions-of-interest (ROI). The intraclass correlation coefficients (ICCs) of the quantified ASL-$${\\text{T}}_{{2}}$$T 2 varied across brain regions. When averaged across subjects and postlabeling delays (PLDs), the ICCs ranged from reasonable values in parietal regions (ICC = 0.56) to smaller values in frontal regions (ICC = 0.36). Corresponding subject-averaged within-subject coefficients of variation (WSCVs) showed good test–retest measurement precision ($${\\text{WSCV}}_{{{\\text{PLD}}} \\le 0.14$$WSCV PLD ≤ 0.14 for all PLDs), but more pronounced inter-subject variance. Reliability and precision of quantified ASL-$${\\text{T}}_{{2}}$$T 2 were region-, PLD- and subject-specific, showing fair to robust results in occipital, parietal and temporal ROIs. The results give rise to consider the method for future cerebral studies, where variable perfusion or altered$${\\text{T}}_{{2}}$$T 2 times are suspected.

Arterial spin labeling (ASL) is increasingly applied for cerebral blood flow mapping, but [Formula: see text] relaxation of the ASL signal magnetization is often ignored, although it may be clinically relevant. To investigate the extent, to which quantitative [Formula: see text] values in gray matter (GM) obtained by pseudocontinuous ASL (pCASL) perfusion MRI can be reproduced, are reliable and a potential neuroscientific biomarker, a prospective study was performed with ten healthy volunteers (5F,28 ± 3y) at a 3 T scanner. A [Formula: see text]-prepared pCASL sequence enabled the measurement of quantitative [Formula: see text] and perfusion maps. [Formula: see text] times were modeled per voxel and analyzed within four GM-regions-of-interest (ROI). The intraclass correlation coefficients (ICCs) of the quantified ASL-[Formula: see text] varied across brain regions. When averaged across subjects and postlabeling delays (PLDs), the ICCs ranged from reasonable values in parietal regions (ICC = 0.56) to smaller values in frontal regions (ICC = 0.36). Corresponding subject-averaged within-subject coefficients of variation (WSCVs) showed good test-retest measurement precision ([Formula: see text] for all PLDs), but more pronounced inter-subject variance. Reliability and precision of quantified ASL-[Formula: see text] were region-, PLD- and subject-specific, showing fair to robust results in occipital, parietal and temporal ROIs. The results give rise to consider the method for future cerebral studies, where variable perfusion or altered [Formula: see text] times are suspected.Arterial spin labeling (ASL) is increasingly applied for cerebral blood flow mapping, but [Formula: see text] relaxation of the ASL signal magnetization is often ignored, although it may be clinically relevant. To investigate the extent, to which quantitative [Formula: see text] values in gray matter (GM) obtained by pseudocontinuous ASL (pCASL) perfusion MRI can be reproduced, are reliable and a potential neuroscientific biomarker, a prospective study was performed with ten healthy volunteers (5F,28 ± 3y) at a 3 T scanner. A [Formula: see text]-prepared pCASL sequence enabled the measurement of quantitative [Formula: see text] and perfusion maps. [Formula: see text] times were modeled per voxel and analyzed within four GM-regions-of-interest (ROI). The intraclass correlation coefficients (ICCs) of the quantified ASL-[Formula: see text] varied across brain regions. When averaged across subjects and postlabeling delays (PLDs), the ICCs ranged from reasonable values in parietal regions (ICC = 0.56) to smaller values in frontal regions (ICC = 0.36). Corresponding subject-averaged within-subject coefficients of variation (WSCVs) showed good test-retest measurement precision ([Formula: see text] for all PLDs), but more pronounced inter-subject variance. Reliability and precision of quantified ASL-[Formula: see text] were region-, PLD- and subject-specific, showing fair to robust results in occipital, parietal and temporal ROIs. The results give rise to consider the method for future cerebral studies, where variable perfusion or altered [Formula: see text] times are suspected.

Arterial spin labeling (ASL) is increasingly applied for cerebral blood flow mapping, but T 2 relaxation of the ASL signal magnetization is often ignored, although it may be clinically relevant. To investigate the extent, to which quantitative T 2 values in gray matter (GM) obtained by pseudocontinuous ASL (pCASL) perfusion MRI can be reproduced, are reliable and a potential neuroscientific biomarker, a prospective study was performed with ten healthy volunteers (5F,28 ± 3y) at a 3 T scanner. A T 2 -prepared pCASL sequence enabled the measurement of quantitative T 2 and perfusion maps. T 2 times were modeled per voxel and analyzed within four GM-regions-of-interest (ROI). The intraclass correlation coefficients (ICCs) of the quantified ASL- T 2 varied across brain regions. When averaged across subjects and postlabeling delays (PLDs), the ICCs ranged from reasonable values in parietal regions (ICC = 0.56) to smaller values in frontal regions (ICC = 0.36). Corresponding subject-averaged within-subject coefficients of variation (WSCVs) showed good test–retest measurement precision ( WSCV PLD ≤ 0.14 for all PLDs), but more pronounced inter-subject variance. Reliability and precision of quantified ASL- T 2 were region-, PLD- and subject-specific, showing fair to robust results in occipital, parietal and temporal ROIs. The results give rise to consider the method for future cerebral studies, where variable perfusion or altered T 2 times are suspected.

Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry‐based tool that enables point‐wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point‐wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age‐ and gender‐matched healthy subjects. FreeSurfer‐based segmentations of hippocampal subfields in 3T‐MRI were subjected to a geometry‐based analysis that resulted in a coordinate system of the hippocampal mid‐surface and allowed for point‐wise measurements of hippocampal thickness and other features. Using point‐wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS‐mTLE). In the contralateral hippocampus of HS‐mTLE and the affected hippocampus of MRI‐negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS‐mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni‐corrected p < .05). We show that point‐wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application. Hippocampal volumetry is an essential tool in researching and diagnosing neurological diseases, such as mesial temporal lobe epilepsy. However, it is limited in its ability to detect subtle alterations in hippocampal morphometry. In this study, we establish and apply a novel geometry‐based tool that enables point‐wise morphometric analysis based on an intrinsic coordinate system of the hippocampus and compare this new approach to conventional volumetry in individuals with mesial temporal lobe epilepsy.

Here, we report a consanguineous family harboring a novel homozygous frame-shift mutation in ASPM leading to a truncation of the ASPM protein after amino acid position 1830. The phenotype of the patients was associated with microcephaly, epilepsy, and behavioral and cognitive deficits. Despite the obvious genetic similarity, the affected patients show a considerable phenotypic heterogeneity regarding the degree of mental retardation, presence of epilepsy and MRI findings. Interestingly, the degree of mental retardation and the presence of epilepsy correlates well with the severity of abnormalities detected in brain MRI. On the other hand, we detected no evidence for substantial nonsense-mediated ASPM transcript decay in blood samples. This indicates that other factors than ASPM expression levels are relevant for the variability of structural changes in brain morphology seen in patients with primary hereditary microcephaly caused by ASPM mutations.