Deep learning models have achieved remarkable success in segmenting brain white matter lesions in multiple sclerosis (MS), becoming integral to both research and clinical workflows. While brain lesions have gained significant attention in MS research, the involvement of spinal cord lesions in MS is relatively understudied. This is largely owing to the variability in spinal cord magnetic resonance imaging (MRI) acquisition protocols, high individual anatomical differences, the complex morphology and size of spinal cord lesions, and lastly, the scarcity of labeled datasets required to develop robust segmentation tools. As a result, automatic segmentation of spinal cord MS lesions remains a significant challenge. Although some segmentation tools exist for spinal cord lesions, most have been developed using sagittal T2-weighted (T2w) sequences primarily focusing on cervical spines. With the growing importance of spinal cord imaging in MS, axial T2w scans are becoming increasingly relevant due to their superior sensitivity in detecting lesions compared to sagittal acquisition protocols. However, most existing segmentation methods struggle to effectively generalize to axial sequences due to differences in image characteristics caused by the highly anisotropic spinal cord scans. To address these challenges, we developed a robust, open-source lesion segmentation tool tailored specifically for axial T2w scans covering the whole spinal cord. We investigated key factors influencing lesion segmentation, including the impact of stitching together individually acquired spinal regions, straightening the spinal cord, and comparing the effectiveness of 2D and 3D convolutional neural networks (CNNs). Drawing on these insights, we trained a multi-center model using an extensive dataset of 582 MS patients, resulting in a dataset comprising an entirety of 2,167 scans. We empirically evaluated the model's segmentation performance across various spinal segments for lesions with varying sizes. Our model significantly outperforms the current state-of-the-art methods, providing consistent segmentation across cervical, thoracic, and lumbar regions. To support the broader research community, we integrate our model into the widely-used Spinal Cord Toolbox (v7.0 and above), making it accessible via the command sct_deepseg lesion_ms_axial_t2 -i .

Background A growing arsenal of treatment options for relapsing multiple sclerosis (RMS) emphasises the need for early prognostic biomarkers. While evidence for individual markers exists, comprehensive analyses at the time of diagnosis are sparse. Methods Brain and spinal cord lesion numbers, cerebrospinal fluid parameters, initial symptoms, and Expanded Disability Status Scale (EDSS) score were determined at the time of diagnosis. Confirmed disability accumulation (CDA), defined as a sustained EDSS increase over 6 months, was determined during a 5-year follow-up. All-subsets multivariable logistic regression was performed to identify predictors of CDA. Model performance was assessed via receiver operating characteristic analysis, and individual risks were calculated. Analyses were repeated with progression independent of relapse activity (PIRA) as an outcome. Results 113/417 (27.1%) people with RMS experienced CDA on follow-up. Intrathecal IgG synthesis, a higher number of spinal cord lesions, age and polysymptomatic manifestation were identified as independent predictors of CDA. The resulting prediction model yielded an area under the curve (AUC) of 0.75 with a 95% CI of 0.70 to 0.80. Individuals exceeding the optimal thresholds for the three most significant predictors had a 61.8% likelihood of experiencing CDA, whereas those below all three thresholds had a CDA rate of 4.5%. The only significant baseline predictor differentiating PIRA from relapse-associated worsening was a higher number of spinal cord lesions (AUC=0.64, 95% CI 0.54 to 0.74). Conclusions Intrathecal IgG synthesis, spinal cord lesion number, age and polysymptomatic manifestation are independent predictors of early CDA in newly diagnosed RMS.

Myocardial injury, indicated by an elevation of high-sensitive cardiac Troponin (hs-cTnT), is a frequent stroke-related complication. Most studies investigated patients with ischemic stroke, but only little is known about its occurrence in patients with intracerebral hemorrhage (ICH). This study aimed to assess the frequency, predictors, and implications of myocardial injury in ICH patients. Our retrospective analysis included 322 ICH patients. We defined myocardial injury as an elevation of hs-cTnT above the 99th percentile (i.e. 14 ng/L). Acute myocardial injury was defined as either a changing pattern of > 50

Spine MRIs are usually acquired in highly anisotropic 2D axial or sagittal slices. Vertebra structures are not fully resolved in these images, and multi-image superresolution by aligning scans to pair them is difficult due to partial volume effects and inter-vertebral movement during acquisition. Hence, we propose an unpaired inpainting superresolution algorithm that extrapolates the missing spine structures. We generate synthetic training pairs by multiple degradation functions that model the data shift and acquisition errors between sagittal slices and sagittal views of axial images. Our method employs modeling of the k-space point spread function and the interslice gap. Further, we imitate different MR acquisition challenges like histogram shifts, bias fields, interlace movement artifacts, Gaussian noise, and blur. This enables the training of diffusion-based superresolution models on scaling factors larger than 6$\times$ without real paired data. The low z-resolution in axial images prevents existing approaches from separating individual vertebrae instances. By applying this superresolution model to the z-dimension, we can generate images that allow a pre-trained segmentation model to distinguish between vertebrae and enable automatic segmentation and processing of axial images. We experimentally benchmark our method and show that diffusion-based superresolution outperforms state-of-the-art super-resolution models.

Abstract Introduction In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients. Methods ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing–Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing–Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed. Perspective Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)—ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034

Background Conventional brain magnetic resonance imaging (MRI) produces image intensities that have an arbitrary scale, hampering quantification. Intensity scaling aims to overcome this shortfall. As neurodegenerative and inflammatory disorders may affect all brain compartments, reference regions within the brain may be misleading. Here we summarize approaches for intensity scaling of conventional T1-weighted (w) and T2w brain MRI avoiding reference regions within the brain. Methods Literature was searched in the databases of Scopus, PubMed, and Web of Science. We included only studies that avoided reference regions within the brain for intensity scaling and provided validating evidence, which we divided into four categories: 1) comparative variance reduction, 2) comparative correlation with clinical parameters, 3) relation to quantitative imaging, or 4) relation to histology. Results Of the 3825 studies screened, 24 fulfilled the inclusion criteria. Three studies used scaled T1w images, 2 scaled T2w images, and 21 T1w/T2w-ratio calculation (with double counts). A robust reduction in variance was reported. Twenty studies investigated the relation of scaled intensities to different types of quantitative imaging. Statistically significant correlations with clinical or demographic data were reported in 8 studies. Four studies reporting the relation to histology gave no clear picture of the main signal driver of conventional T1w and T2w MRI sequences. Conclusions T1w/T2w-ratio calculation was applied most often. Variance reduction and correlations with other measures suggest a biologically meaningful signal harmonization. However, there are open methodological questions and uncertainty on its biological underpinning. Validation evidence on other scaling methods is even sparser.

Automated segmentation of brain white matter lesions is crucial for both clinical assessment and scientific research in multiple sclerosis (MS). Over a decade ago, we introduced an engineered lesion segmentation tool, LST. While recent lesion segmentation approaches have leveraged artificial intelligence (AI), they often remain proprietary and difficult to adopt. As an open-source tool, we present LST-AI, an advanced deep learning-based extension of LST that consists of an ensemble of three 3D U-Nets.LST-AI explicitly addresses the imbalance between white matter (WM) lesions and non-lesioned WM. It employs a composite loss function incorporating binary cross-entropy and Tversky loss to improve segmentation of the highly heterogeneous MS lesions. We train the network ensemble on 491 MS pairs of T1-weighted and FLAIR images, collected in-house from a 3T MRI scanner, and expert neuroradiologists manually segmented the utilized lesion maps for training. LST-AI also includes a lesion location annotation tool, labeling lesions as periventricular, infratentorial, and juxtacortical according to the 2017 McDonald criteria, and, additionally, as subcortical. We conduct evaluations on 103 test cases consisting of publicly available data using the Anima segmentation validation tools and compare LST-AI with several publicly available lesion segmentation models.Our empirical analysis shows that LST-AI achieves superior performance compared to existing methods. Its Dice and F1 scores exceeded 0.62, outperforming LST, SAMSEG (Sequence Adaptive Multimodal SEGmentation), and the popular nnUNet framework, which all scored below 0.56. Notably, LST-AI demonstrated exceptional performance on the MSSEG-1 challenge dataset, an international WM lesion segmentation challenge, with a Dice score of 0.65 and an F1 score of 0.63—surpassing all other competing models at the time of the challenge. With increasing lesion volume, the lesion detection rate rapidly increased with a detection rate of >75% for lesions with a volume between 10 mm3 and 100 mm3.Given its higher segmentation performance, we recommend that research groups currently using LST transition to LST-AI. To facilitate broad adoption, we are releasing LST-AI as an open-source model, available as a command-line tool, dockerized container, or Python script, enabling diverse applications across multiple platforms.

Recent years have seen a growing interest in methods for predicting an unknown variable of interest, such as a subject's diagnosis, from medical images depicting its anatomical-functional effects. Methods based on discriminative modeling excel at making accurate predictions, but are challenged in their ability to explain their decisions in anatomically meaningful terms. In this paper, we propose a simple technique for single-subject prediction that is inherently interpretable. It augments the generative models used in classical human brain mapping techniques, in which the underlying cause-effect relations can be encoded, with a multivariate noise model that captures dominant spatial correlations. Experiments demonstrate that the resulting model can be efficiently inverted to make accurate subject-level predictions, while at the same time offering intuitive visual explanations of its inner workings. The method is easy to use: training is fast for typical training set sizes, and only a single hyperparameter needs to be set by the user. Our code is available at https://github.com/chiara-mauri/Interpretable-subject-level-prediction.

BACKGROUND:Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges.METHODS:We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients.FINDINGS:We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data.INTERPRETATION:We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination.FUNDING:This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01).