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Introduction: Neuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post-stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO PET quantification method includes a 90 min scan and continuous arterial blood sampling, which is challenging to perform on a routine basis. In this work, we determine what information is required for a simplified quantification approach using a machine learning algorithm., Materials and Methods: We analyzed data from 18 patients with ischemic stroke who received 0-90 min [ 18 F]GE-180 PET as well as T1-weigted (T1w), FLAIR, and arterial spin labeling (ASL) MRI scans. During PET scans, five manual venous blood samples at 5, 15, 30, 60, and 85 min post injection (p.i.) were drawn, and plasma activity concentration was measured. Total distribution volume (V T ) was calculated using Logan plot with the full dynamic PET and an image-derived input function (IDIF) from the carotid arteries. IDIF was scaled by a calibration factor derived from all the measured plasma activity concentrations. The calculated V T values were used for training a random forest regressor. As input features for the model, we used three late PET frames (60-70, 70-80, and 80-90 min p.i.), the ASL image reflecting perfusion, the voxel coordinates, the lesion mask, and the five plasma activity concentrations. The algorithm was validated with the leave-one-out approach. To estimate the impact of the individual features on the algorithm's performance, we used Shapley Additive Explanations (SHAP). Having determined that the three late PET frames and the plasma activity concentrations were the most important features, we tested a simplified quantification approach consisting of dividing a late PET frame by a plasma activity concentration. All the combinations of frames/samples were compared by means of concordance correlation coefficient and Bland-Altman plots., Results: When using all the input features, the algorithm predicted V T values with high accuracy (87.8 ± 8.3%) for both lesion and non-lesion voxels. The SHAP values demonstrated high impact of the late PET frames (60-70, 70-80, and 80-90 min p.i.) and plasma activity concentrations on the V T prediction, while the influence of the ASL-derived perfusion, voxel coordinates, and the lesion mask was low. Among all the combinations of the late PET frames and plasma activity concentrations, the 70-80 min p.i. frame divided by the 30 min p.i. plasma sample produced the closest V T estimate in the ischemic lesion., Conclusion: Reliable TSPO PET quantification is achievable by using a single late PET frame divided by a late blood sample activity concentration., (Copyright © 2022. Published by Elsevier GmbH.)

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., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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., (© 2023. The Author(s).)

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.

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., Competing Interests: MG receives royalties from Siemens Healthineers for technology using ASL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Neumann, Schidlowski, Günther, Stöcker and Düzel.)

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.

The bias in favour of isotopically light carbon inherent in biological carbon fixation has brought about an isotopic disproportionation of primordial (mantle-derived) carbon on a global scale, causing an enrichment of 12C in reduced (biogenic) carbon and a concomitant accumulation of the heavy complement (13C) in the residual oxidized (inorganic) carbon pool. As a result, the terrestrial carbon cycle has gone bipartite, comprising an organic branch of isotopically light carbon, and an inorganic branch made up of 13C-enriched carbon (mostly in the form of carbonate). The isotopic disparity between the two principal terrestrial carbon species can be traced back over 3.8 Gyr of Earth history, attesting to a biological modulation of the carbon cycle since the time of formation of the oldest sediments.

In contrast to the search for extant organisms, the quest for fossil remains of life on Mars need not be guided by the presence of water and organic compounds on the present surface. An appropriate tracer might be the element phosphorus which is a common constituent of living systems. Utilizing terrestrial analogues, it should preferentially exist in the form of sedimentary calcium phosphate (phosphorites), which would have readily resisted changing conditions on Mars. Moreover, higher ratios of P/Th in phosphorites in comparison to calcium phosphates from magmatic rocks give us the possibility to distinguish them from inorganically formed phosphorus deposits at or close to the Martian surface. Identification of anomalous phosphorus enrichments by remote sensing or in situ analysis could be promising approaches for selecting areas preferentially composed of rocks with remains of extinct life.

With the currently available geological record at band, the existence of life on this planet as from at least 3.8 Gyr ago seems so firmly established as to be virtually unassailable. Specifically, various disparate lines of evidence have merged to indicate (1) that the surface of the Archaean Earth had hosted prolific microbial ecosystems as is testified by a quasi-continuous record of microbialites ("stromatolites") and associated microfossils of prokaryotic affinity over 3.5, if not 3.8 Gyr of geological history, and (2) that the sedimentary carbon record has preserved the isotopic signature of autotrophic (notably photosynthetic) carbon fixation over the same time span. With the observed enrichment of isotopically light carbon in sedimentary organic matter largely consonant with the bias in favor of 12C during photosynthesis, the mainstream of the carbon isotope record can be best explained as geochemical manifestation of the isotope discriminating properties of the ribulose-1,5-bisphosphate (RuBP) carboxylase reaction of the Calvin cycle suggesting an extreme degree of evolutionary conservatism in the biochemistry of autotrophic carbon fixation. As a consequence, partial biological control of the geochemical carbon cycle was established already during Early Archaean times and fully operative by the time of formation of the Earth's earliest sediments.

Organic and inorganic carbon in terrestrial near-surface environments are characterized by a marked difference in their 13C/12C ratios which can be traced back in the Earth's sedimentary record over almost 4 billion years. There is no doubt that the bias in favour of 12C displayed by biogenic matter derives, for the most part, from the isotope-selecting properties of the carbon-fixing enzyme (ribulose-1,5-bisphosphate carboxylase) that is operative in the principal photosynthetic pathway and promotes most of the carbon transfer from the non-living to the living realm. Postulating a universality of biological principles in analogy to the proven universality of the laws of physics and chemistry, we may expect enzymatic reactions in exobiological systems to be beset with B similar kinetic fractionation effects. Hence, the retrieval from the oldest Martian sediments of isotopic fractionations between reduced and oxidized (carbonate) carbon may substantially constrain current conjectures on the possible existence of former life on Mars.

The characteristic difference of some 20 to 30% in the 13C/12C ratios of reduced (organic) and oxidized (carbonate) carbon as observed in the contemporary environment can be traced back over 3.5 (if not 3.8) Ga of recorded Earth history. There is little doubt that the enrichment of isotopically light carbon in fossil organic matter ultimately derives from the bias in favor of 12C during photosynthetic carbon fixation (notably the RuBP carboxylase reaction of the Calvin cycle). Accordingly, the mainstream of the sedimentary delta 13Corg record can be most reasonably explained as geochemical evidence of the isotope-discriminating properties of the principal CO2-fixing enzymatic reaction of the assimilatory pathway, thus giving eloquent testimony to an extreme degree of evolutionary conservatism in the biochemistry of autotrophic carbon fixation.

Polymerized hydrocarbons occurring in the gold-uranium conglomerates of the Witwatersrand System (South Africa) show deltaC(13) values between -22.4 and -32.8 per mille, their isotopic composition thus falling into the range of sedimentary organic carbon. Accordingly, organic derivation of the material seems very probable. This conclusion is consistent with a model of the existence of organic evolution and biologic activity in times certainly older than 2.15 x 10(9) years.