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.

Purpose of reviewBrain MRI is central to the diagnostic work-up of autoimmune encephalitis (AE). This review summarizes established patterns on routine MRI sequences across antibody-defined AE types and highlights emerging quantitative and network-based approaches aimed at improving sensitivity, phenotypic stratification, and prognostication.Recent findingsConventional MRI reveals syndrome-associated patterns that can support diagnosis in several AE types, including medial temporal involvement in LGI1, CASPR2, and GABA(B) receptor encephalitis; multifocal cortico-subcortical lesions in GABA(A) receptor encephalitis, and radial perivascular enhancement in GFAP astrocytopathy. Longitudinal studies show that regional and global atrophy better reflect cumulative injury and clinical outcome than acute lesions in entities such as NMDA receptor encephalitis or IgLON5 antibody-mediated disease. Basic quantitative measures derived from routine sequences can detect microstructural abnormalities in normal-appearing tissue. Advanced techniques including quantitative MRI, diffusion tensor imaging, and resting-state functional MRI demonstrate widespread structural and functional network disruption beyond visible lesions. Translational animal studies further link imaging changes to antibody-mediated synaptic dysfunction.SummaryConventional MRI remains indispensable for differential diagnosis and pattern recognition in AE. Pragmatic approaches such as volumetry and basic quantitative metrics are closest to clinical implementation, whereas advanced techniques require further standardization and validation. Together, these developments position MRI to evolve from a primarily diagnostic tool toward precision phenotyping, prognosis, and longitudinal monitoring in AE.

BACKGROUND AND OBJECTIVES:Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E. METHODS:In this cross-sectional study, we combined clinical assessments, comprehensive neuropsychological testing, diffusion tensor MRI, probabilistic WM tractography, and computational network analysis in patients with LGI1-E referred to Charité-Universitätsmedizin Berlin. Healthy individuals were recruited as control participants and matched to patients for age and sex with logistic regression propensity scores. RESULTS:Twenty-five patients with LGI1-E (mean age = 63 ± 12 years, 76% male) and 25 healthy controls were enrolled. Eighty-eight percent of patients presented persistent cognitive symptoms at postacute follow-up (median: 12 months from onset, interquartile range: 6-23 months)-despite treatment with immunotherapy and good overall recovery (modified Rankin Scale [mRS] score at peak illness vs postacute: z = -4.1, p < 0.001, median mRS score at postacute visit: 1). Neuroimaging revealed that WM networks in LGI1-E are characterized by (1) a systematic reduction in whole-brain connectivity (t = -2.16, p = 0.036, d = -0.61), (2) a cortico-subcortical hypoconnectivity cluster affecting both limbic and extralimbic brain systems, and (3) a "topological reorganization" marked by a bidirectional shift in the relative importance of individual brain regions in the WM network. The extent of this WM reorganization was strongly associated with long-term deficits of verbal memory (r = -0.56), attention (r = -0.55), and executive functions (r = -0.60, all pFDR = 0.017). DISCUSSION:Although traditionally viewed as a form of limbic encephalitis, our study characterizes LGI1-E as a "network disorder" that affects the whole brain. Structural reorganization of WM networks was linked to long-term and multidomain cognitive impairment, which was not prevented by immunotherapy. These findings highlight the need for closer monitoring and improved treatment strategies to mitigate long-term cognitive impairment in LGI1-E.

Background:Visual symptoms are common in people with multiple sclerosis. The revised 2024 McDonald criteria include the optic nerve as a fifth anatomical region, underscoring the need for specific diagnostics. Although optical coherence tomography (OCT) and visual evoked potentials (VEP) are available, the extent of their routine pre-referral use is insufficiently documented. We evaluated pre-referral utilization and hypothesized that specific diagnostics are used less often than non-specific diagnostics and that differences are not explained by demographics alone. Methods:Retrospective cross-sectional study of 305 patients referred for visual symptoms to a tertiary neuroimmunology clinic in Germany. Analyses focused on people with multiple sclerosis (n = 112) and disease controls with neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein-associated disease (pwNM; n = 36). Results:In people with multiple sclerosis, only 6.2% received OCT and 33% VEP for their visual complaints, compared to unspecific diagnostics such as cranial magnetic resonance imaging (58%) and lumbar puncture (42%) - independent of demographic factors. Conclusion:The pre-referral use of specific neurovisual tests in people with multiple sclerosis with visual symptoms was low relative to non-specific procedures. This suggests heterogeneous integration of neurovisual testing across care levels. In light of the revised McDonald Criteria 2024, prospective multicenter studies should examine implementation and clinical impact.

ABSTRACT Background Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The disease hallmarks cortical lesion, central vein sign (CVS) and paramagnetic rim lesions identified in MS have not yet been comprehensively investigated in MOGAD. Methods We have characterized 45 patients with MOGAD using 7.0 Tesla (7 T) MRI at two academic research hospitals in China and Germany. 7 T MRI, laboratory, and clinical data were collected. The classification of cortical lesions, proportion of CVS, and the phase shifts of lesions on susceptibility weighted imaging were analyzed. Results Of the 45 patients enrolled with MOGAD, 282 lesions were identified. We further detected 31 (11%) cortical lesions including leukocortical, intracortical, and subpial types, of which intracortical lesions (16/31, 52%) were frequently involved. CVS was identified in 53 (19%) lesions of 21 (47%) patients, 154 (55%) lesions showed multiple veins sign (MVS) in 30 (67%) patients. The number (4.3 ± 6.0 vs. 1.5 ± 2.1, p = 0.0049) and percentage (52% vs. 18%, p < 0.0001) of MVS lesions for each MOGAD patient were higher than those of CVS. Eight patients (18%) had 39 (14%) lesions of hypointense signal with paramagnetic phase shifts on SWI, showing nodular phase changes and irregular borders in appearance. Conclusions In our observational MOGAD cohort, all three types of cortical lesions were recognized, with intracortical lesions being the most common. The number and proportion of lesions with MVS were higher than those with CVS. Lesions with paramagnetic phase changes were rare and non‐rim‐like in appearance. These findings provide a better understanding of the underlying pathology of MOGAD and will help in the differentiation of MOGAD from other demyelinating disorders.

Autoimmune encephalitis encompasses a spectrum of conditions characterized by distinct clinical features and magnetic resonance imaging (MRI) findings. Here, we review the literature on acute MRI changes in the most common autoimmune encephalitis variants. In N-methyl-D-aspartate (NMDA) receptor encephalitis, most patients have a normal MRI in the acute stage. When lesions are present in the acute stage, they are typically subtle and non-specific white matter lesions that do not correspond with the clinical syndrome. In some NMDA receptor encephalitis cases, these T2-hyperintense lesions may be indicative of an NMDA receptor encephalitis overlap syndrome with simultaneous co-existence of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Encephalitis with leucine-rich glioma-inactivated 1 (LGI1)-, contactin-associated protein-like 2 (CASPR2)- or glutamic acid decarboxylase (GAD)- antibodies typically presents as limbic encephalitis (LE) with unilateral or bilateral T2/fluid attenuated inversion recovery (FLAIR) hyperintensities in the medial temporal lobe that can progress to hippocampal atrophy. Gamma aminobutyric acid-B (GABA-B) receptor encephalitis also often shows such medial temporal hyperintensities but may additionally involve cerebellar lesions and atrophy. Gamma aminobutyric acid-A (GABA-A) receptor encephalitis features multifocal, confluent lesions in cortical and subcortical areas, sometimes leading to generalized atrophy. MRI is unremarkable in most patients with immunoglobulin-like cell adhesion molecule 5 (IgLON5)-disease, while individual case reports identified T2/FLAIR hyperintense lesions, diffusion restriction and atrophy in the brainstem, hippocampus and cerebellum. These findings highlight the need for MRI studies in patients with suspected autoimmune encephalitis to capture disease-specific changes and to exclude alternative diagnoses. Ideally, MRI investigations should be performed using dedicated autoimmune encephalitis imaging protocols. Longitudinal MRI studies play an important role to evaluate potential relapses and to manage long-term complications. Advanced MRI techniques and current research into imaging biomarkers will help to enhance the diagnostic accuracy of MRI investigations and individual patient outcome prediction. This will eventually enable better treatment decisions with improved clinical outcomes.

IntroductionVery rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E. Here, we aimed to investigate the frequency, long-term outcome, and immunological concomitants of ataxia in NMDAR-E.MethodsIn this observational study, patients with definite NMDAR-E with a follow-up of >12 months were recruited from the GENERATE registry. Cases with documented ataxia were analyzed in detail.ResultsIn 12 of 62 patients (19%), ataxia was documented. Bilateral cerebellar ataxia without additional focal CNS findings was found in four (one child and three adults); one of these was previously reported as a case with persistent cerebellar atrophy and ataxia. Two patients with bilateral cerebellar ataxia had additional focal neurological symptoms, optic neuritis and facial palsy. Two patients developed hemiataxia: one with diplopia suggesting brainstem dysfunction and the other probably resulting from cerebellar diaschisis due to contralateral status epilepticus. In all but the one developing cerebellar atrophy, cerebellar ataxia was transient and not associated with a worse long-term outcome. In all five patients with cerebellar ataxia tested, MOG, AQP-4, GluK2, and KLHL11 antibodies were negative. In two additional patients negative for both MOG and AQP-4 antibodies, ataxia was sensory and explained by cervical myelitis as part of multiple sclerosis (MS) manifesting temporal relation to NMDAR-E. One of the patients with bilateral ataxia with focal neurological deficits was also diagnosed with MS upon follow-up. Finally, in two patients, ataxia was explained by cerebral hypoxic damage following circulatory failure during an ICU stay with severe NMDAR-E.DiscussionAtaxia of different types is quite common in NMDAR-E. Cerebellar ataxia in NMDAR-E is mostly transient. NMDAR-E followed by persistent ataxia and cerebellar atrophy is very rare. Cerebellar ataxia in NMDAR-E may not be explained by concomitant KLHL11, MOG, AQP-4, or GluK2 autoimmunity. Of note, ataxia in NMDAR-E may result from treatment complications and, most interestingly, from MS manifesting in temporal association with NMDAR-E.

Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune encephalitis with a variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction and clinical symptoms are largely unknown. Aiming for analyses from the molecular to the clinical level, we isolated antibody-secreting cells from the cerebrospinal fluid of two patients with CASPR2 encephalitis. From these we cloned four anti-CASPR2 human monoclonal autoantibodies (mAbs) with strong binding to brain and peripheral nerves. All were highly hypermutated and mainly of the IgG4 subclass. Mutagenesis studies determined selective binding to the discoidin domain of CASPR2. Surface plasmon resonance revealed affinities with dissociation constants KD in the pico- to nanomolar range. CASPR2 mAbs interrupted the interaction of CASPR2 with its binding partner contactin 2 in vitro and were internalized after binding to CASPR2-expressing cells. Electrophysiological recordings of rat hippocampal slices after stereotactic injection of CASPR2 mAbs showed characteristic afterpotentials following electrical stimulation. In vivo experiments with intracerebroventricular administration of human CASPR2 mAbs into mice and rats showed EEG-recorded brain hyperexcitability but no spontaneous recurrent seizures. Behavioral assessment of infused mice showed a subtle clinical phenotype, mainly affecting sociability. Mouse brain MRI exhibited markedly reduced resting-state functional connectivity without short-term structural changes. Together, the experimental data support the direct pathogenicity of CASPR2 autoantibodies. The minimally invasive EEG and MRI techniques applied here may serve as novel objective, quantifiable tools for improved animal models, in particular for subtle neuropsychiatric phenotypes or repeated measurements.

Background Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. Methods We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre. Results We found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts. Conclusion Combining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.

Structured Abstract Importance Despite immunotherapy, most patients with anti–leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E) develop long-term cognitive deficits that persist for years after peak illness. However, the structural brain changes that underlie these deficits remain poorly understood. Objective To study the relationship between cognitive outcomes and white matter (WM) networks in LGI1-E. Design Cross-sectional study. Setting German university center (Charité - Universitätsmedizin Berlin). Participants 25 patients with LGI1-E (19/25 male [76%], mean age: 63 ± 12 years) and 25 age- and sex-matched healthy controls (HC), recruited between January 2013 and April 2019. Main Outcomes and Measures Clinical assessments including the modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE); comprehensive cognitive testing; WM tractography using diffusion-weighted MRI. Results All patients had received first-line immunotherapy, and two-thirds underwent second-line immunotherapy. Patients showed a significant reduction in mRS scores from peak illness to post-acute follow-up ( z = -3.8, p < 0.001, n = 20), with 85% presenting “good” functional outcomes (post-acute mRS ≤ 2), paralleled by a significant reduction in CASE scores ( z = -3.5, p < 0.001, n = 20). Despite this overall improvement, however, cognitive symptoms were highly prevalent at peak illness (95% of patients affected) and strongly persisted into the post-acute disease stage (85% affected). Neuroimaging at post-acute follow-up (median: 12 months from onset) revealed that LGI1-E is characterized by (i) significantly reduced whole-brain structural connectivity ( t = -2.16, p = 0.036, d = -0.61), (ii) a cortico-subcortical hypoconnectivity cluster that strongly affects the hippocampus but also severely impacts extra-limbic brain systems, (iii) systematic limbic and extra-limbic decreases in node degree — a graph-theoretical measure of overall connectedness, and (iv) a “topological reorganization” of structural brain networks, marked by a bidirectional shift in the relative importance of individual brain regions in the network. Importantly, the extent of this network reorganization was significantly related to persistent cognitive deficits in the domains of verbal memory ( r = -0.57, p = 0.007, n = 21), attention ( r = -0.47, p = 0.030, n = 21), and executive functions ( r = -0.60, p = 0.010, n = 17). Conclusion and Relevance This study characterizes LGI1-E as a network disease that affects both limbic and extra-limbic brain systems and shows that a reorganization of WM networks is linked to multi-domain cognitive deficits in the post-acute disease stage – despite immunotherapy and good overall recovery. These findings highlight the need for extended treatment strategies to improve long-term cognitive outcomes and propose a sensitive new neuroimaging marker to include in prospective clinical trials. Key Points Question What structural brain changes underlie the persistent cognitive deficits observed in patients with anti–leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E)? Findings This cross-sectional study shows that LGI1-E is characterized by a structural reorganization of white matter networks that affects both limbic and extra-limbic brain systems and correlates with persistent deficits in verbal memory, attention, and executive functions at post-acute follow-up – despite immunotherapy and good overall clinical recovery. Meaning This study characterizes LGI1-E as a network disease –beyond focal damage to the limbic system– and shows that persistent cognitive deficits relate to immunotherapy-resistant changes in structural brain networks, highlighting the need for extended treatment strategies to improve long-term cognitive outcomes.

AbstractObjectivePrevalence, susceptibility genes, and clinical and radiological features may differ across different ethnic groups of multiple sclerosis (MS). We aim to characterize brain lesions in Chinese patients with MS by use of 7‐T MRI.MethodsMS participants were enrolled from the ongoing China National Registry of Neuro‐Inflammatory Diseases (CNRID) cohort. 7‐T MRI of the brain was performed. Each lesion was evaluated according to a standardized procedure. Central vein sign (CVS) and paramagnetic rim lesions were identified. The characteristics of lesions at patient‐level and at lesion‐level from previous 7‐T MRI literature were also summarized.ResultsWe included 120 MS patients. Their mean (SD) age was 34.6 (9.4) years. The female‐to‐male ratio was 1.7:1 and mean disease duration of patients with MS was 5.5 ± 6.1 years. The median EDSS score was 2 (range, 0–8). A total of 8502 lesions were identified with a median lesion count of 45 (IQR, 18–90) (range, 2–370). The median (IQR) percentage for these special locations were as follows: cortical lesions (CLs) 2.7% (0%–5.7%), juxtacortical lesions 16.2% (7.8%–25.7%), periventricular lesions 30.2% (17.2%–38.7%), and infratentorial lesions 5.8% (0.4%–11.9%). CLs occurred in 70 (58%) patients, accounting for only 443 (5%) of the total lesions. Out of the 443 CLs, 309 (69.8%) were leukocortical lesions. CVS appeared in 5392 (63%) lesions from 117 (98%) patients. 1792 (21%) lesions and 104 (87%) patients exhibited a paramagnetic rim.InterpretationOur study elaborated on the lesion features of Chinese patients with MS by use of 7‐T MRI. Lesion burden is heavy in Chinese patients with MS. The median lesion count and proportion of PRL are high. The reported heavy lesion burden calls for ramping up regional and global efforts to care for MS patients. The management and research of Chinese population with MS needs to be further strengthened.

Background Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis. Methods Structural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome. Results Patients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001). Conclusions Focal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls. Multilayer networks were constructed using mutual information for topological analysis, and Boolean simulations were constructed using Pearson correlation to identified paths within and among all layers. The path more commonly found from the Boolean simulations connects protein MK03, with total T cells, the thickness of the retinal nerve fiber layer (RNFL), and the walking speed. This path contains nodes involved in protein phosphorylation, glial cell differentiation, and regulation of stress-activated MAPK cascade, among others. Specific paths identified were subsequently analyzed by flow cytometry at the single-cell level. Combinations of several proteins (GSK3AB, HSBP1 or RS6) and immune cells (Th17, Th1 non-classic, CD8, CD8 Treg, CD56 neg, and B memory) were part of the paths explaining the clinical phenotype. The advantage of the path identified from the Boolean simulations is that it connects information about these known biological pathways with the layers at higher scales (retina damage and disability). Overall, the identified paths provide a means to connect the molecular aspects of MS with the overall phenotype.

Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders. Using rs-fMRI, we studied functional connectivity alterations in (1) adult C57BL/6 J mice that were intrathecally injected with a recombinant human NR1 antibody over 14 days ( n = 10) and in (2) a newly established mouse model with in utero exposure to a human recombinant NR1 antibody (NR1-offspring) at the age of (2a) 8 weeks ( n = 15) and (2b) 10 months ( n = 14). Adult NR1-antibody injected mice showed impaired functional connectivity within the left hippocampus compared to controls, resembling impaired connectivity patterns observed in human NMDAR encephalitis patients. Similarly, NR1-offspring showed significantly reduced functional connectivity in the hippocampus after 8 weeks, and impaired connectivity in the hippocampus was likewise observed in NR1-offspring at the age of 10 months. We successfully reproduced functional connectivity changes within the hippocampus in different experimental murine systems that were previously observed in human NMDAR encephalitis patients. Translational application of this method within a combined imaging and histopathological framework will allow future experimental studies to identify the underlying biological mechanisms and may eventually facilitate non-invasive monitoring of disease activity and treatment responses in autoimmune encephalitis.

IgG antibodies that bind to the N-methyl-D-aspartate receptors (NMDAR-Ab) can be detected in up to 1 % of healthy individuals. This suggests that a considerable subgroup of pregnant women is at risk of transferring NMDAR-antibodies to the fetus. We ask whether a transient in utero exposure to human NMDAR-Ab can lead to neural network defects in adulthood. In mouse model of maternofetally transferred human NMDAR-Ab, at P51, corresponding to early adulthood in humans, we conducted two-photon calcium imaging in awake behaving mice. We found that microcircuits in NMDAR-Ab exposed mice exhibited a lower spontaneous activity and increased bursty firing. Upon visual stimulation, neurons in NMDAR-Ab exposed mice had a higher orientation selectivity. In NMDAR-Ab exposed mice, a large fraction of neurons active upon visual stimulation did not fire spontaneously, and vice versa . This dissociation is in sharp contrast to the operational principles in healthy networks, in which the majority of all neurons were co-active. These findings suggest that transient in utero exposure to NMDAR-Ab shifts cortical microcircuits to a maladaptive state persisting into adulthood, characterized by a dissociation between spontaneous and visually evoked activity. Such dissociation has long been hypothesized to play a role in the development of psychosis.### Competing Interest StatementThe authors have declared no competing interest.

(1) Background: Radial RARE-EPI MRI facilitates simultaneous T2 and T2* mapping (2in1-RARE-EPI). With modest undersampling (R = 2), the speed gain of 2in1-RARE-EPI relative to Multi-Spin-Echo and Multi-Gradient-Recalled-Echo references is limited. Further reduction in scan time is crucial for clinical studies investigating T2 and T2* as imaging biomarkers. We demonstrate the feasibility of further acceleration, utilizing compressed sensing (CS) reconstruction of highly undersampled 2in1-RARE-EPI. (2) Methods: Two-fold radially-undersampled 2in1-RARE-EPI data from phantoms, healthy volunteers (n = 3), and multiple sclerosis patients (n = 4) were used as references, and undersampled (Rextra = 1–12, effective undersampling Reff = 2–24). For each echo time, images were reconstructed using CS-reconstruction. For T2 (RARE module) and T2* mapping (EPI module), a linear least-square fit was applied to the images. T2 and T2* from CS-reconstruction of undersampled data were benchmarked against values from CS-reconstruction of the reference data. (3) Results: We demonstrate accelerated simultaneous T2 and T2* mapping using undersampled 2in1-RARE-EPI with CS-reconstruction is feasible. For Rextra = 6 (TA = 01:39 min), the overall MAPE was ≤8% (T2*) and ≤4% (T2); for Rextra = 12 (TA = 01:06 min), the overall MAPE was <13% (T2*) and <5% (T2). (4) Conclusion: Substantial reductions in scan time are achievable for simultaneous T2 and T2* mapping of the brain using highly undersampled 2in1-RARE-EPI with CS-reconstruction.