Liver MRI plays a critical role in the diagnosis and monitoring of liver disease; however, image quality is often degraded by respiratory motion and noise, particularly in high-resolution and diffusion-weighted imaging. Propeller-based sequences such as BLADE improve motion robustness, but advanced reconstruction strategies are required to fully exploit their potential under accelerated conditions. We propose a phase-constrained zero-shot self-supervised learning (PC ZS-SSL) framework for BLADE liver MRI reconstruction. The method embeds BLADE forward and adjoint operators within an unrolled deep network together with an explicit phase estimation module. Unlike supervised approaches, PC ZS-SSL requires no external training data and instead leverages partitioned k-space. The framework was first evaluated using structured phantom experiments assessing spatial resolution and low-contrast detectability, and subsequently applied to in vivo 3 T T2-weighted (T2W, 20 blades) and diffusion-weighted imaging (DWI, 18 and 15 blades, b = 0, 800 s/mm2). Performance was compared with locally low-rank (LLR) and vendor-provided reconstructions. In phantom studies, PC ZS-SSL preserved fine structural details and demonstrated improved sharpness compared with fewer gradient updates and LLR. In vivo, PC ZS-SSL consistently reduced noise and ringing artifacts while maintaining anatomical fidelity. In T2W imaging, it achieved image quality comparable to LLR with fewer artifacts. In DWI, where noise is more pronounced, PC ZS-SSL provided clearer organ boundaries than both LLR and vendor reconstructions. Additional in vivo evaluation demonstrated that PC ZS-SSL remained robust under severe undersampling conditions (e.g., 4 blades) and challenging imaging scenarios, where LLR reconstructions exhibited residual artifacts. PC ZS-SSL enables high-quality, artifact-suppressed BLADE liver MRI without the need for external training data. Its strong performance in both phantom and in vivo experiments—particularly under high-noise diffusion conditions—highlights its potential for clinical translation.

Spatial navigation deficits emerge early in Alzheimer's disease and related dementias (ADRD), yet their potential as a training target and source of digital biomarkers remains underexplored. We evaluated a smartphone-based, unsupervised wayfinding training in 58 cognitively unimpaired older adults and characterized multi-day learning trajectories derived from digital behavioral readouts in relation to neurobiological risk and reserve markers. Participants completed six training sessions navigating to points-of-interest on a university campus, with continuous GPS and app interaction recording. Compared with walking-only controls, participants improved in a pointing task and map drawing, but not in a visuospatial memory task. Higher MTL tau was associated with reduced improvements in navigation efficiency in individuals with greater hippocampal vessel distance. Higher cerebrovascular dysfunction was linked to attenuated learning on readouts reflecting information-processing demands. These findings demonstrate that real-world digital navigation training improves spatial cognition and multi-day learning trajectories show domain-specific associations with ADRD-related biomarkers.

OBJECTIVE:Immune effector cell-associated neurotoxicity syndrome (ICANS) is the most frequent neurological complication following chimeric antigen receptor (CAR)-T cell therapy. Long-term cognitive effects remain controversial, even in the absence of clinical neurotoxicity. CAR-T cell-associated neurotoxicity often involves the medial temporal lobe (MTL), yet conventional structural magnetic resonance imaging (MRI) frequently remains normal. There is a need for markers of subclinical neurotoxicity that may predict long-term cognitive outcomes. METHODS:Therefore, we established an imaging protocol integrating 3 Tesla (T) and 7 T perfusion and functional connectivity MRI of the MTL in patients receiving CAR-T cells for B cell malignancies. Longitudinal data from four patients is presented here. RESULTS:Two of the four patients developed ICANS (grade 1 and grade 3), and these patients also experienced mild cytokine release syndrome (CRS, grade 1). No structural abnormalities of the MTL were detected at baseline or during follow-up. CAR-T cell expansion varied markedly between patients. Regardless of ICANS, CRS, or CAR-T cell expansion, patients showed increased MTL perfusion and functional connectivity, most prominently at days 10-14. CONCLUSION:These data suggest an early, clinically silent inflammatory response in the MTL with potential implications for long-term cognitive function, which requires further investigation.

The role of inflammation in cortical superficial siderosis (cSS), a marker of cerebral amyloid angiopathy (CAA) linked to high hemorrhage risk, is unclear. We examined 15 patients with cSS using 3 T post-contrast vessel wall MRI (VWI) and CSF analysis. Although only 27% met current CAA-ri criteria, 93% showed vessel wall enhancement or sulcal hyperintensities near cSS, frequently extending beyond. Seven patients with follow-up VWI demonstrated corticosteroid-responsive regression of inflammation. CSF albumin quotients, indicating blood-brain barrier dysfunction, correlated with MRI inflammation scores. These findings reveal subclinical meningovascular inflammation in cSS and support VWI for detecting a broader CAA-related inflammation spectrum.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex vivo investigations, the in vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrate the feasibility of describing the three-layered myelin architecture of CA1 in vivo, and provide information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

ABSTRACT Purpose To demonstrate the synergy of undersampled radial 2in1‐RARE‐EPI acquisition and nonlinear model‐based reconstruction for accelerated and simultaneous T 2 , T 2 *, and R 2 ′ mapping in brains of patients with multiple sclerosis (MS). Methods 2in1‐RARE‐EPI combines a RARE module with an EPI module to capture T 2 and T 2 * information. Nonlinear model‐based reconstruction was applied to estimate T 2 , T 2 * maps directly from undersampled k ‐space data. A retrospective undersampling experiment was conducted to compare nonlinear model‐based and parallel imaging compressed sensing (PICS) reconstruction. The proposed approach was validated and compared to reference methods multiecho spin‐echo ( T 2 , MSE) and multiecho gradient‐echo ( T 2 *, MGRE) in a phantom, healthy subjects, and MS patients. Results 2in1‐RARE‐EPI together with nonlinear model‐based reconstruction enabled T 2 , T 2 *, and R 2 ′ mapping with 7.5‐fold scan‐time acceleration relative to the references, while addressing key limitations of reference techniques, including long acquisition times, misregistration, motion and off‐resonance sensitivity, and the need for calibration scans. Phantom and in vivo validation showed that the parametric maps obtained with this approach were in agreement with the reference methods. Compared with PICS, nonlinear model‐based reconstruction showed more consistent spatial detail and accuracy at higher acceleration factors. The proposed method detected small focal lesions in T 2 , T 2 *, and R 2 ′ maps of MS patients and enabled visualization of the central vein sign. Conclusion Scan time reduction facilitated by nonlinear model‐based reconstruction of 2in1‐RARE‐EPI provides a technical foundation for enhanced patient compliance, and is a fundamental precursor for broader clinical studies on the potential of T 2 , T 2 *, and R 2 ′ as imaging biomarkers.

BACKGROUND:Centrum semiovale perivascular spaces (CSO PVS) are common to different cerebral small vessel disease (CSVD) subtypes, yet their enlargement to the point of visibility on magnetic resonance imaging is thought to occur through distinct mechanisms. In cerebral amyloid angiopathy (CAA), CSO PVS are thought to reflect impaired perivascular Aβ (amyloid-β) drainage, whereas in deep perforator arteriopathy (DPA) they may result from microangiopathy-related arterial stiffening and altered fluid dynamics. The extent to which this can be confirmed in vivo remains unclear. METHODS:We retrospectively analyzed 186 patients with CSVD and cerebrospinal fluid (CSF) Aβ biomarkers (n=111 probable CAA, n=75 DPA). CSO PVS were counted on axial T2-weighted images. Associations between CSO PVS and CSF biomarkers were assessed via Pearson correlation and multivariable linear regression, including an interaction term between CSF Aβ and CSVD subtype, adjusted for demographics and neuroimaging markers of CSVD. RESULTS:Patients with higher CSO PVS counts were generally younger, had lower white matter hyperintensity burden, higher basal ganglia PVS counts, and were more frequently affected by cortical superficial siderosis. CSO PVS counts were similar in patients with CAA and DPA. The association between CSF Aβ42/40 ratio and CSO PVS burden was observed in patients with CAA, but not in those with DPA (interaction term between CSF Aβ42/40 ratio and CAA: β=-0.27; P=0.016), independent of demographics and other neuroimaging markers of CSVD. CSF Aβ40 showed no association with CSO PVS counts in any model. CONCLUSIONS:Our findings strengthen the pathophysiological link between CSO PVS and Aβ pathology in CAA but not in DPA. These results extend previous histopathologic and neuroimaging work and underscore the need to interpret CSO PVS in the context of underlying CSVD subtype.

Chronic psychosocial stress (CPS) is associated with adverse brain and mental health outcomes. Effects on the cerebral microvasculature have been proposed as an underlying mechanism, although this remains to be established. Here, we examined the association between CPS and an early marker of microvascular dysfunction, magnetic resonance imaging (MRI)-visible perivascular spaces (PVS). Analyses were conducted in two cohorts of healthy young adults (N = 61; ages 18-43 years; 88% male) using high-resolution 3T MRI and an automated PVS quantification pipeline. CPS was assessed using the Perceived Stress Scale (PSS-10). We applied a two-step meta-analytic framework and controlled for known allostatic factors impacting PVS, including age, body mass index and mean arterial pressure. In accordance with our hypothesis, individuals with higher CPS had significantly higher fractional PVS volumes in the centrum semiovale (CSO), in particular in the frontal and occipital lobes (pFDR < .05). No such effect was found in the basal ganglia, or in the CSO subdivision, parietal, and temporal lobes (pFDR > .09). Our findings indicate that CPS may contribute to subtle, centrum semiovale specific microvascular alterations even in healthy young adults. Future multimodal research including inflammatory marker and blood-brain barrier measures may help to elucidate mechanistic pathways. ### Competing Interest Statement MW is a member of the following advisory boards and gave presentations to the following companies: Boehringer Ingelheim, Germany; and Biologische Heilmittel Heel GmbH, Germany. MW has further conducted studies with institutional research support from Biologische Heilmittel Heel GmbH and Janssen Pharmaceutical Research unrelated to this investigation. VE is a member of the advisory board of Biologische Heilmittel Heel GmbH, Germany. LH is currently employed by Biologische Heilmittel Heel GmbH. All companies had no role in the design, conduct, or reporting of this study. All other authors report no biomedical financial interests or other potential conflicts of interest. ### Funding Statement The present work was supported by: for LC Interdisciplinary Center of Clinical Research of the Medical Faculty Jena (AMS-21), Federal Ministry for Research, Technology and Aeronautics through German Center for Mental Health (01EE2507F); for MW Eberhard Karls University Tuebingen Fortune Projekt (nr. 2394-0-0), BMFTR (16SV8590), BMFTR through DZPG (01EE2305A/01EE2305F; 01EE2505A/01EE2505F; 01EE2507F). Computational PVS quantification was supported by The Galen and Hilary Weston Foundation under the Novel Biomarkers 2019 scheme (ref UB190097) administered by the Weston Brain Institute and the Row Fogo Centre for Research into Ageing and the Brain (AD.ROW4.35. BRO-D.FID3668413). It is also funded by UK Dementia Research Institute funded by UKDRI Ltd which received its funding from the UK Medical Research Council, Alzheimer Society and Alzheimer's Research UK (DRIEdi17/18, UKDRI-4002 UKDRI-4205). Funding sources had no role in the study design, data collection, analysis, and interpretation, the writing of the report, and the decision to submit the article for publication. Open Access funding enabled and organized by Project DEAL. We acknowledge support by the German Research Foundation Projekt-Nr. 512648189 and the Open Access Publication Fund of the Thueringer Universitaets- und Landesbibliothek Jena. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study 1 was approved by the Ethical committee of Jena University Hospital (2022-2718-1-BO). Study 2 was approved by the Ethical committee of Medical Faculty of Eberhard Karls University Tuebingen (578/2016B01). All participants gave written informed consent and were reimbursed for their participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

MRI-visible perivascular spaces (PVS) are increasingly recognised as markers of compromised brain health, but their quantitative use requires segmentation methods that remain reliable beyond the datasets on which they were developed. Whether current methods meet this requirement remains unclear. To address this gap, we organised the Domain Randomisation PVS (DoRA-PVS) Challenge, a no-data-shared benchmark designed to evaluate out-of-sample PVS segmentation in two settings: an open method track for previously published methods, and a domain randomisation track for new strategies trained exclusively on synthetic data. The testbed comprised 285 images from 12 cohorts, capturing substantial heterogeneity in scanner vendors, field strengths, sequences, imaging protocols, image quality, and participant characteristics. Four teams competed in the first DoRA-PVS Challenge: two in the open method track, one in the domain-randomisation track, and one in both tracks. Preliminary results show that external generalisation is achievable. Across tracks, most methods achieved AUPRC values above random-classifier performance on unseen data, indicating that they could segment PVS beyond their development cohorts. However, this generalisation was not consistent: performance varied substantially across cohorts and evaluation metrics. These preliminary findings shift the central question from whether PVS segmentation methods can generalise at all to whether they can generalise reliably across heterogeneous data. The DoRA-PVS Challenge therefore establishes a rigorous benchmark for assessing out-of-sample robustness and provides a framework for developing PVS segmentation methods that are more consistent across acquisition protocols, populations, and anatomical regions.

Background: Blood-brain barrier (BBB) dysfunction is increasingly recognized as a feature of cerebral amyloid angiopathy (CAA) and has been linked to hemorrhagic imaging manifestations such as cortical superficial siderosis. However, it remains unclear whether neurovascular barrier dysfunction can be captured by routinely available fluid biomarkers and whether such markers identify clinically relevant hemorrhage-prone CAA phenotypes. The CSF/serum albumin quotient (QAlb) is an established marker of neurovascular barrier dysfunction. We investigated QAlb levels in CAA and their association with imaging markers of disease severity. Methods: We included 225 participants (115 with CAA, 72 with Alzheimers disease [AD], 38 healthy controls) with CSF biomarkers and standardized MRI evaluation. Pathologic QAlb levels were identified via the age-corrected Reiber-formula. Group differences and determinants of pathological QAlb were assessed using uni- and multivariable regression analyses. The diagnostic relevance was assessed by receiver operating characteristic analysis. Results: QAlb levels were higher in CAA than in controls (ratio of means [RoM] 1.43, 95% CI 1.28-1.58) and patients with AD (RoM 1.22, 95% CI 1.10-1.35; both p<0.001). Pathological QAlb was independently associated with CAA compared with controls (OR 12.16, 95% CI 2.56-57.86) and AD (OR 2.14, 95% CI 1.07-4.28). Despite these associations, QAlb showed only moderate discrimination between CAA and controls (AUC 0.75, 95% CI 0.67-0.82) and low discrimination between CAA and AD (AUC 0.63, 95% CI 0.55-0.71). Within the CAA cohort, pathological QAlb was independently associated with disseminated cortical superficial siderosis (OR 3.92, 95% CI 1.31-11.72; p=0.014), a marker of advanced hemorrhage-prone disease. Conclusion: QAlb is elevated in patients with CAA and is associated with disseminated cortical superficial siderosis, the strongest predictor of future intracerebral hemorrhage. These findings support an association between neurovascular barrier dysfunction and the hemorrhage-prone phenotype of CAA. ### Competing Interest Statement The authors have declared no competing interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The local Clinical Ethics Committee approved this retrospective study (Ethikkommission, Otto-von-Guericke-Universität Magdeburg; no. 07/17, addendum 11/2021). The study was performed in accordance with the relevant local and national guidelines and regulations I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

OBJECTIVE:Accurately predicting future hemorrhagic events in patients with cerebral amyloid angiopathy (CAA) remains a major clinical challenge. It is unknown whether cerebrospinal fluid (CSF) biomarkers of amyloid-beta (Aβ) pathology are associated with increased hemorrhage risk in this population. METHODS:We analyzed consecutive patients meeting Boston criteria version 2.0 for probable CAA with CSF Aβ data obtained during diagnostic workup. The primary outcome was incident intracranial hemorrhage, including lobar intracerebral, convexity subarachnoid, and non-traumatic subdural hemorrhage. Secondary outcomes were ischemic stroke and all-cause mortality. Associations between low CSF Aβ biomarkers and outcomes were analyzed using Cox proportional hazards models, adjusted for disseminated cortical superficial siderosis, and prior intracerebral hemorrhage. RESULTS:Among 109 patients (median age: 77 years, 42% female), 16 (15%) experienced incident intracranial hemorrhage and 11 (10%) incident ischemic stroke during a median follow-up of 2.93 years (interquartile range: 1.43-5.03). In multivariate Cox regression models low CSF Aβ biomarkers were independently associated with incident intracranial hemorrhage (Aβ40: hazard ratio: 8.04; [95% CI: 2.43-26.59], p < 0.001; Aβ42: hazard ratio 7.10; [95% CI: 1.58-32.00], p = 0.011). CSF Aβ biomarkers were not associated with incident ischemic strokes and all-cause mortality. A composite risk score integrating low CSF Aβ biomarkers and hemorrhagic imaging features identified a high-risk subgroup with 78% hemorrhage incidence (7/9 patients) and a no-risk group without events (0/42 patients). INTERPRETATION:Low CSF Aβ biomarkers are independently associated with future symptomatic hemorrhage in CAA patients. A composite risk score may support individualized risk stratification and guide clinical decision-making. ANN NEUROL 2026;100:391-399.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons in primary motor cortex, leading to muscle weakness, atrophy and death within a median of 3 years. Even though ALS is characterized by different disease subtypes affecting different body parts, individualized phenotyping of functional ALS pathology has so far not been achieved. We recorded 7 Tesla functional MRI data while ALS patients and matched controls moved affected and non-affected body parts in the MR scanner. We applied robust Shared Response Modelling for capturing ALS-specific shared responses for group classification, and Partial Least Squares regression for relating the latent variables to clinical subtypes and the degree of disease progression. We show that disease onset and severity can be best modelled by functional connectivity rather than local activation changes. We also show that functional disease-defining information in primary motor cortex is not the strongest in the area that is behaviourally first-affected, deviating from the behavioural phenotype of the patients. When computing the model's weight distribution of the King stage classification and projecting them back into voxel space, the highest mean weights are present in the foot and tongue/face regions. Our data highlight the importance of 7 Tesla functional MRI task-based functional connectivity measures for classifying ALS patients in addition to structural readouts and provides evidence that a 7 Tesla functional MRI can be used for identifying a disease signature of each individual ALS patient.

Tactile fingertip sensations are critical for everyday life. Accordingly, tactile fingertip maps have been extensively studied in human primary somatosensory cortex. However, the fine-grained functional architecture of these maps remains largely unknown. To uncover this architecture, we sought to estimate 2D spatio-tactile population receptive fields (pRFs) of the tip of the index finger in human Brodmann area 3b (BA3b). Using functional magnetic resonance imaging at 7T and submillimeter resolution along with prospective motion correction, we recorded brain responses while participants sensed a row of vibrotactile pins sweeping along cardinal axes over a portion of the fingertip. To estimate pRF position and size, we initially fit a 2D Gaussian pRF model to the data, which, however, produced largely implausible pRF estimates. Simulations indicated that this likely occurred because the size of pRFs in BA3b surpasses the portion of the fingertip we stimulated, resulting in an incomplete mapping of pRFs. To address this issue, we constrained the fitting procedure and refined the 2D Gaussian pRF model by keeping pRF size constant. Our results for pRF position then revealed that the ulnar-to-radial axis spanning the fingertip maps onto a superior-to-inferior axis in BA3b. Both the putatively large pRF size (relative to the mapping area) and the pRF position gradient we uncover here appear compatible with receptive field properties quantified in monkeys. Our study provides the first comprehensive investigation into the fine-grained functional architecture of human fingertip maps and brings us one step closer to a thorough understanding thereof.

Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of this study was to investigate associations between IFSH and CSVD, and their potential repercussions, i.e., cognitive impairment and depression. We prospectively recruited 47 patients with CSVD and 29 cognitively normal controls (NC). IFSH were rated visually based on FLAIR MRI. Using different regression models, we explored the relationship between IFSH, group status (CSVD vs. NC), CSVD severity assessed with MRI, cognitive function, and symptoms of depression. Patients with CSVD were more likely to have higher IFSH scores compared to NC (OR 5.64, 95% CI 1.91-16.60), and greater CSVD severity on MRI predicted more severe IFSH (OR 1.47, 95% CI 1.14-1.88). Higher IFSH scores were associated with lower cognitive function (-0.96, 95% CI -1.81 to -0.10), and higher levels of depression (0.33, 95% CI 0.01-0.65). CSVD and IFSH may be tightly linked to each other, and the accumulation of waste products, indicated by IFSH, could have detrimental effects on cognitive function and symptoms of depression.

Background Recurrent hemorrhage represents a significant risk for patients with lobar hemorrhage and underlying cerebral amyloid angiopathy. However, it remains unknown, whether cerebrospinal fluid biomarkers of β‐amyloid (Aβ) retention, predict recurrent hemorrhagic events in these patients. Methods In this retrospective study, we evaluated patients with first‐ever lobar intracerebral hemorrhage or convexity subarachnoid hemorrhage who underwent cerebrospinal fluid analysis of Aβ40, Aβ42, and Aβ42/40 ratio. Biomarker levels were compared between patients with and without recurrent hemorrhage, and optimal cutoff values were derived from receiver operating characteristic analysis to define high and low biomarker groups. Negative binomial regression models, adjusted for age, sex, and hypertension, were used to assess associations with recurrent hemorrhage rates, and Kaplan–Meier survival analysis evaluated time to first event as a sensitivity measure. Results Among 289 patients with lobar hemorrhage, 48 were eligible for analysis (mean age, 72.4 years; 44% women; median follow‐up, 2.7 years). Patients with recurrent hemorrhage had significantly lower Aβ40 and Aβ42 levels (P<0.05). Those with low Aβ42 levels exhibited a recurrence rate of 18.2 versus 1.7 events per 100 patient‐years (incidence rate ratio, 12.7 [95% CI, 1.5–306.6]; P=0.035; sensitivity, 89%; specificity, 54%), while low Aβ40 levels were associated with 63.6 versus 4.5 events per 100 patient‐years (incidence rate ratio, 41.0 [95% CI, 5.8–434.4]; P<0.001; sensitivity, 44%; specificity, 95%). Combining probable cerebral amyloid angiopathy (Boston criteria version 1.5) with low Aβ40 levels improved risk stratification, yielding a rule‐in specificity of 75% and a rule‐out sensitivity of 100%. Additionally, the Aβ42/40 ratio demonstrated robust accuracy for identifying probable cerebral amyloid angiopathy (sensitivity, 63%; specificity, 83%). Conclusions Cerebrospinal fluid Aβ biomarkers are effective in predicting recurrent hemorrhage and identifying probable cerebral amyloid angiopathy in patients with lobar hemorrhage. These findings underscore the potential of disease‐specific biofluid markers to improve clinical risk stratification and guide management strategies.

To date, all computerised perivascular spaces (PVS) quantification methods require case-wise, imaging modality, or study-specific parameter adjustments, and suffer from generalisability problems in clinical settings, and misdetection of other cerebral small vessel disease (CSVD) markers. We propose a deep learning-based PVS detection method to overcome these issues. We compare our proposal on magnetic resonance imaging data of CSVD participants against the performance of the Frangi filter. T1-weighted (T1w) and T2-weighted (T2w) neuroimaging data from 16 patients with severe CSVD were collected at the Hospital of the Otto-von-Guericke University Magdeburg. PVS across the entire brain tissue were manually segmented in T2w images by a medical student. We extended SynthSeg ( https://surfer.nmr.mgh.harvard.edu/fswiki/SynthSeg ) for PVS detection (Figure 1). PVS-SynthSeg, our proposal, is based on a convolutional neural network and trained using synthetic data sampled from a generative model that relies on brain atlases as a conditioning factor, as well as domain randomisation. We incorporated tubular structures into such brain atlases to expand the model’s capabilities for the identification of PVS. This provides PVS-SynthSeg with the ability to detect PVS in scans from diverse scanners and protocols without requiring additional fine-tuning or parameter adjustments. We compared the precision and recall of PVS-SynthSeg against that from the Frangi filter on both imaging modalities. The Frangi filter detected the majority of PVS in both T1w and T2w scans, albeit with high false positive rates–recall of approximately 80% and precision below 30% (Figure 2). PVS-SynthSeg had more variability in recall but near-one precision across both modalities, despite the presence of white matter hyperintensities (WMH). We propose a deep learning-based PVS detection algorithm. In a small sample, PVS-SynthSeg detected PVS in T1w and T2w scans better than the Frangi filter without additional adjustments, even in scans affected by motion artefacts or with WMH. These findings highlight the promise of PVS-SynthSeg as a modular and effective PVS detection method, however larger cohort testing needs to be conducted. Better PVS quantification can help us shed light into the role of PVS in CSVD and Alzheimer’s disease.

OBJECTIVE:In cerebral small vessel disease (CSVD), compromised arterial supply to the deep gray matter contributes to cognitive decline. While CSVD frequently involves lenticulostriate arteries supplying the putamen, the functional consequences of altered putaminal vascular architecture remain unclear. We hypothesized that a less homogeneous arterial network in the putamen is associated with impaired perfusion and worse cognitive performance in CSVD. METHODS:We enrolled 16 CSVD patients with cerebral microbleeds and 21 age‑matched controls (mean age 71 years; 38 % female). High-resolution 7 T time‑of‑flight angiography was used to segment all visible intraputaminal vessels. For each voxel in the putamen, the distance to its nearest segmented vessel was computed to generate a vessel distance map; the mean vessel distance reflects the homogeneity of the arterial network. Putaminal perfusion was quantified via multi‑inversion time pulsed arterial spin labeling (ASL) at 3 T, and CSVD severity was scored on clinical 3 T MRI. All participants completed a comprehensive neuropsychological battery to derive a global cognition composite score. RESULTS:Linear regression revealed that higher CSVD MRI scores predicted larger mean vessel distance, reflecting a sparser arterial network, in both the right (B = 0.12, β = 0.42, p = 0.010) and left putamen (B = 0.13, β = 0.43, p = 0.014). Across all participants, increased vessel distance was also associated with prolonged arterial transit time in the right (B = 0.044, β = 0.50, p = 0.009) and left putamen (B = 0.042, β = 0.49, p = 0.009). Finally, in a multivariable linear regression adjusting for demographics, vascular risk factors, and CSVD severity, greater vessel distance in the right putamen was associated with lower global cognitive performance (B = -1.26, β = -0.34, p = 0.012). CONCLUSION:This study demonstrates the impact of an impaired arterial network in the putamen on blood supply and cognitive function across the continuum of CSVD.

Acute sleep deprivation is known to impair vigilance performance and alter brain physiology. This study investigates structural, physiological and cognitive effects of one night of sleep deprivation (SD) and subsequent recovery. Thirty healthy participants underwent (18M/12F, mean age 28.0 ± 4.7 years, range 20-38) a multimodal assessment including 7T MRI, plasma biomarker analysis, and Psychomotor Vigilance Task (PVT) testing at three time points: baseline, after 24 h of SD, and following a 72-h recovery period. Our results demonstrate that SD induced a significant increase in total perivascular space (PVS) volume (from 6711.5 mm3 to 7475.3 mm3; p < 0.001), a marker of impaired glymphatic function, which completely normalized after recovery. These macrostructural changes were accompanied by reversible microstructural alterations, including decreased T1 relaxation times and shifts in quantitative susceptibility mapping (QSM) in multiple brain regions, indicative of dynamic fluid shifts. Systemically, SD led to an increase in pro-inflammatory markers, notably MMP-9 (from 52.3 pg/mL to 69.2 pg/mL; p < 0.05), and changes in multiple peripheral biomarkers. Behaviorally, participants exhibited significantly more attentional lapses (slowest 10 % RT: 386.4 ms-410 ms; p < 0.05), which were also reversed upon recovery. In conclusion, a single night of SD triggers a cascade of interconnected and fully reversible physiological changes, likely initiated by transient glymphatic disruption. Healthy individuals are able to recover mostly from one night of SD, suggesting that adverse effects of SD, when not in a chronic state, can potentially be reversed.

Leveraging high-resolution 7 T magnetic resonance imaging (MRI) and vessel distance mapping (VDM), the arterial supply patterns and dominances of the motor cortex, which could previously only be studied postmortem, were assessed in vivo and fully noninvasively. Beyond vessel patterns and dominances, the potential relation between the vascularization and the motor cortex thickness was studied. Twenty-one healthy participants underwent 7 T MRI scans to map arterial supply and motor cortex at 0.45 mm isotropic resolution. The motor cortex vasculature was segmented manually with vessel-specific labels. VDM was utilized to estimate the vessel-specific supply regions and, subsequently, assess vessel patterns and dominances. Statistical tests were applied to test if the vasculature impacts mean motor cortical thickness estimates. Vessel patterns, that is the presence of supplying vessels, were classified as three-, four-, and five-vessel patterns with a prevalence of 26.3%, 50.0%, and 23.7%, respectively. Vessel dominance, that is the ratio of supply volumes, of the ACA branches showed dominance of the pericallosal artery, callosomarginal artery, and equal contribution, in 34.2%, 34.2%, and 31.6% of the cases, respectively. For the MCA groups, the prevalence of precentral group dominance, central group dominances, and equal contribution was 13.2%, 34.2%, and 52.6%, respectively. Although the central and precentral groups were found in all hemispheres, the postcentral group was found in 28.9% of hemispheres with highly variable supply contribution. Statistical tests returned no significance for the effect of vessel patterns and dominances on the mean motor cortex thickness. With 7 T MRI and VDM, the motor cortex vascularization can be assessed fully noninvasively and longitudinally while providing overall good concordance with previous post mortem studies. Our comprehensive analysis of arterial motor cortex vascularization showed considerable variability between hemispheres, rendering the usage of pattern-specific atlases and analysis more suitable than single normative representations. The successful translation from post mortem to in vivo enables the study of vascular reserve in disorders affecting the motor cortex, such as ALS, and can be translated to other brain regions and neurodegenerative diseases in the future.

Cortical superficial siderosis (cSS) is the strongest marker of future intracranial hemorrhage (ICH) in cerebral amyloid angiopathy (CAA), a condition without disease modifying therapy. Emerging evidence suggests that cSS may reflect meningovascular inflammation potentially amenable to immunosuppression. We conducted a single center matched cohort study comparing high dose corticosteroid therapy versus no immunosuppression in patients with probable CAA and cSS. Treated patients were matched 1:2 to untreated patients by demographics, cSS multifocality, and baseline intracerebral hemorrhage. The primary outcome was incident ICH; secondary outcomes were any cerebrovascular event and mortality. Kaplan Meier analysis assessed event-free survival. cSS progression was evaluated in patients with ≥6 months MRI follow up, and inflammation in a subgroup with post contrast vessel wall imaging (VWI). Thirty six patients were included (12 treated, 24 untreated; mean age 77.4 years; 91% disseminated cSS). Over a median follow-up of 2.23 years, 11 patients had cerebrovascular events (15 ICHs, 3 ischemic strokes), all in the untreated group (p=0.041 for ICH; p=0.037 for any event). Mortality did not differ (p=0.634). cSS progressed in 2/6 (33%) treated versus 4/7 (57%) untreated patients. Baseline VWI detected inflammation in 7/9 patients (78%), which regressed after corticosteroids. Corticosteroid therapy was associated with fewer cerebrovascular events in high risk CAA, supporting prospective controlled validation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the BB-DARS project, funded by the Deutsche Alzheimer Gesellschaft (DAlzG) and the Foerderstiftung Dierichs. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Clinical Ethics Committee of the University Medical Center Magdeburg (Otto von Guericke University Magdeburg, Medical Faculty) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.