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Introduction: Lesion load (LL), deep gray matter (DGM) and normal-appearing white matter (NAWM) susceptibility and morphometry may help in monitoring brain changes in multiple sclerosis (MS) patients. We aimed at evaluating the feasibility of a fully automated segmentation and the potential interrelation between these biomarkers and clinical disability. Methods: Sixty-six patients with brain MRIs and clinical evaluations (Expanded Disability Status Scale [EDSS]) were retrospectively included. Automated prototypes were used for the segmentation and morphometry of brain regions (MorphoBox) and MS lesions (LeManPV). Susceptibility maps were estimated using standard post-processing (RESHARP and TVSB). Spearman’s rho was computed to evaluate the interrelation between biomarkers and EDSS. Results: We found (i) anticorrelations between the LL and right thalamus susceptibility (rho = −0.46, p < 0.001) and between the LL and NAWM susceptibility (rho = [−0.68 to −0.25], p ≤ 0.05); (ii) an anticorrelation between LL and DGM (rho = [−0.71 to −0.36], p < 0.04) and WM morphometry (rho = [−0.64 to −0.28], p ≤ 0.01); and (iii) a positive correlation between EDSS and LL (rho = [0.28 to 0.5], p ≤ 0.03) and anticorrelation between EDSS and NAWM susceptibility (rho = [−0.29 to −0.38], p < 0.014). Conclusions: Fully automated brain morphometry and susceptibility monitoring is feasible in MS patients. The lesion load, thalamus and NAWM susceptibility values and trophicity are interrelated and correlate with disability.

ObjectiveTo assess the accuracy of corpus callosum (CC) biometry, including sub-segments, using 3D super-resolution fetal brain MRI (SR) compared to 2D or 3D ultrasound (US) and clinical low-resolution T2-weighted MRI (T2WS).MethodFetal brain biometry was conducted by two observers on 57 subjects [21–35 weeks of gestational age (GA)], including 11 cases of partial CC agenesis. Measures were performed by a junior observer (obs1) on US, T2WS and SR and by a senior neuroradiologist (obs2) on T2WS and SR. CC biometric regression with GA was established. Statistical analysis assessed agreement within and between modalities and observers.ResultsThis study shows robust SR to US concordance across gestation, surpassing T2WS. In obs1, SR aligns with US, except for genu and CC length (CCL), enhancing splenium visibility. In obs2, SR closely corresponds to US, differing in rostrum and CCL. The anterior CC (rostrum and genu) exhibits higher variability. SR’s regression aligns better with literature (US) for CCL, splenium and body than T2WS. SR is the method with the least missing values.ConclusionSR yields CC biometry akin to US (excluding anterior CC). Thanks to superior 3D visualization and better through plane spatial resolution, SR allows to perform CC biometry more frequently than T2WS.

The benefits, opportunities and growing availability of ultra-high field magnetic resonance imaging (MRI) for humans have prompted an expansion in research and development efforts towards increasingly more advanced high-resolution imaging techniques. To maximize their effectiveness, these efforts need to be supported by powerful computational simulation platforms that can adequately reproduce the biophysical characteristics of MRI, with high spatial resolution. In this work, we have sought to address this need by developing a novel digital phantom with realistic anatomical detail up to 100-µm resolution, including multiple MRI properties that affect image generation. This phantom, termed BigBrain-MR, was generated from the publicly available BigBrain histological dataset and lower-resolution in-vivo 7T-MRI data, using a newly-developed image processing framework that allows mapping the general properties of the latter into the fine anatomical scale of the former. Overall, the mapping framework was found to be effective and robust, yielding a diverse range of realistic “in-vivo-like” MRI contrasts and maps at 100-µm resolution. BigBrain-MR was then tested in three imaging applications (motion effects and interpolation, super-resolution imaging, and parallel imaging reconstruction) to investigate its properties, value and validity as a simulation platform. The results consistently showed that BigBrain-MR can closely approximate the behavior of real in-vivo data, more realistically and with more extensive features than a more classic option such as the Shepp-Logan phantom. Its flexibility in simulating different contrast mechanisms and artifacts may also prove valuable for educational applications. BigBrain-MR is therefore deemed a favorable choice to support methodological development and demonstration in brain MRI, and has been made freely available to the community.

Measurement(s) brain connectivity measurement Technology Type(s) Fiber tracking

Abstract Accurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation.

Introduction: Over the past few years, the deep learning community has developed and validated a plethora of tools for lesion detection and segmentation in Multiple Sclerosis (MS). However, there is an important gap between validating models technically and clinically. To this end, a six-step framework necessary for the development, validation, and integration of quantitative tools in the clinic was recently proposed under the name of the Quantitative Neuroradiology Initiative (QNI).Aims: Investigate to what extent automatic tools in MS fulfill the QNI framework necessary to integrate automated detection and segmentation into the clinical neuroradiology workflow.Methods: Adopting the systematic Cochrane literature review methodology, we screened and summarised published scientific articles that perform automatic MS lesions detection and segmentation. We categorised the retrieved studies based on their degree of fulfillment of QNI’s six-steps, which include a tool’s technical assessment, clinical validation, and integration.Results: We found 156 studies; 146/156 (94%) fullfilled the first QNI step, 155/156 (99%) the second, 8/156 (5%) the third, 3/156 (2%) the fourth, 5/156 (3%) the fifth and only one the sixth.Conclusions: To date, little has been done to evaluate the clinical performance and the integration in the clinical workflow of available methods for MS lesion detection/segmentation. In addition, the socio-economic effects and the impact on patients’ management of such tools remain almost unexplored.

Measurement(s) regional part of brain • T2 (Observed)-Weighted Imaging Technology Type(s) Image Segmentation Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14039327

Fetal brain diffusion magnetic resonance images (MRI) are often acquired with a lower through-plane than in-plane resolution. This anisotropy is often overcome by classical upsampling methods such as linear or cubic interpolation. In this work, we employ an unsupervised learning algorithm using an autoencoder neural network for single-image through-plane super-resolution by leveraging a large amount of data. Our framework, which can also be used for slice outliers replacement, overperformed conventional interpolations quantitatively and qualitatively on pre-term newborns of the developing Human Connectome Project. The evaluation was performed on both the original diffusion-weighted signal and the estimated diffusion tensor maps. A byproduct of our autoencoder was its ability to act as a denoiser. The network was able to generalize fetal data with different levels of motions and we qualitatively showed its consistency, hence supporting the relevance of pre-term datasets to improve the processing of fetal brain images.

Magnetic Resonance Imaging (MRI) is an established technique to study in vivo neurological disorders such as Multiple Sclerosis (MS). To avoid errors on MRI data organization and automated processing, a standard called Brain Imaging Data Structure (BIDS) has been recently proposed. The BIDS standard eases data sharing and processing within or between centers by providing guidelines for their description and organization. However, the transformation from the complex unstructured non-open file data formats coming directly from the MRI scanner to a correct BIDS structure can be cumbersome and time consuming. This hinders a wider adoption of the BIDS format across different study centers. To solve this problem and ease the day-to-day use of BIDS for the neuroimaging scientific community, we present the BIDS Managing and Analysis Tool (BMAT). The BMAT software is a complete and easy-to-use local open-source neuroimaging analysis tool with a graphical user interface (GUI) that uses the BIDS format to organize and process brain MRI data for MS imaging research studies. BMAT provides the possibility to translate data from MRI scanners to the BIDS structure, create and manage BIDS datasets as well as develop and run automated processing pipelines, and is faster than its competitor. BMAT software propose the possibility to download useful analysis apps, especially applied to MS research with lesion segmentation and processing of imaging contrasts for novel disease biomarkers such as the central vein sign and the paramagnetic rim lesions.

Introduction: Multiple Sclerosis (MS) is a common neurological disease primarily characterized by myelin damage in lesions and in normal - appearing white and gray matter (NAWM, NAGM).Several quantitative MRI (qMRI) methods are sensitive to myelin characteristics by measuring specific tissue biophysical properties. However, there are currently few studies assessing the relative reproducibility and sensitivity of qMRI measures to MS pathology in vivo in patients. Methods: We performed two studies. The first study assessed of the sensitivity of qMRI measures to MS pathology: in this work, we recruited 150 MS and 100 healthy subjects, who underwent brain MRI at 3 T including quantitative T1 mapping (qT1), quantitative susceptibility mapping (QSM), magnetization transfer saturation imaging (MTsat) and myelin water imaging for myelin water fraction (MWF). The sensitivity of qMRIs to MS focal pathology (MS lesions vs peri-plaque white/gray matter (PPWM/PPGM)) was studied lesion-wise; the sensitivity to diffuse normal appearing (NA) pathology was measured using voxel-wise threshold-free cluster enhancement (TFCE) in NAWM and vertex-wise inflated cortex analysis in NAGM. Furthermore, the sensitivity of qMRI to the identification of lesion tissue was investigated using a voxel-wise logistic regression analysis to distinguish MS lesion and PP voxels.The second study assessed the reproducibility of myelin-sensitive qMRI measures in a single scanner. To evaluate the intra-session and inter-session reproducibility of qMRI measures, we have investigated 10 healthy subjects, who underwent two brain 3 T MRIs within the same day (without repositioning), and one after 1-week interval. Five region of interest (ROIs) in white and deep grey matter areas were segmented, and inter- and intra- session reproducibility was studied using the intra-class correlation coefficient (ICC). Further, we also investigated the voxel-wise reproducibility of qMRI measures in NAWM and NAGM. Results: qT1 and QSM showed the highest sensitivity to distinguish MS focal WM and cortical pathology from peri-plaque WM (P

The current diagnostic criteria for multiple sclerosis (MS) lack specificity, and this may lead to misdiagnosis, which remains an issue in present-day clinical practice. In addition, conventional biomarkers only moderately correlate with MS disease progression. Recently, some MS lesional imaging biomarkers such as cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL), visible in specialized magnetic resonance imaging (MRI) sequences, have shown higher specificity in differential diagnosis. Moreover, studies have shown that CL and PRL are potential prognostic biomarkers, the former correlating with cognitive impairments and the latter with early disability progression. As machine learning-based methods have achieved extraordinary performance in the assessment of conventional imaging biomarkers, such as white matter lesion segmentation, several automated or semi-automated methods have been proposed as well for CL, PRL, and CVS. In the present review, we first introduce these MS biomarkers and their imaging methods. Subsequently, we describe the corresponding machine learning-based methods that were proposed to tackle these clinical questions, putting them into context with respect to the challenges they are facing, including non-standardized MRI protocols, limited datasets, and moderate inter-rater variability. We conclude by presenting the current limitations that prevent their broader deployment and suggesting future research directions.

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18–34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland–Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume.

Conventional magnetic resonance imaging (cMRI) in multiple sclerosis (MS) patients provides measures of focal brain damage and activity, which are fundamental for disease diagnosis, prognosis, and the evaluation of response to therapy. However, cMRI is insensitive to the damage to the microenvironment of the brain tissue and the heterogeneity of MS lesions. In contrast, the damaged tissue can be characterized by mathematical models on multishell diffusion imaging data, which measure different compartmental water diffusion. In this work, we obtained 12 diffusion measures from eight diffusion models, and we applied a deep-learning attention-based convolutional neural network (CNN) (GAMER-MRI) to select the most discriminating measures in the classification of MS lesions and the perilesional tissue by attention weights. Furthermore, we provided clinical and biological validation of the chosen metrics—and of their most discriminative combinations—by correlating their respective mean values in MS patients with the corresponding Expanded Disability Status Scale (EDSS) and the serum level of neurofilament light chain (sNfL), which are measures of disability and neuroaxonal damage. Our results show that the neurite density index from neurite orientation and dispersion density imaging (NODDI), the measures of the intra-axonal and isotropic compartments from microstructural Bayesian approach, and the measure of the intra-axonal compartment from the spherical mean technique NODDI were the most discriminating (respective attention weights were 0.12, 0.12, 0.15, and 0.13). In addition, the combination of the neurite density index from NODDI and the measures for the intra-axonal and isotropic compartments from the microstructural Bayesian approach exhibited a stronger correlation with EDSS and sNfL than the individual measures. This work demonstrates that the proposed method might be useful to select the microstructural measures that are most discriminative of focal tissue damage and that may also be combined to a unique contrast to achieve stronger correlations to clinical disability and neuroaxonal damage.

Introduction: During the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood. Methods: GAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure. Results: In the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes.Methods: Thirty-two RRMS patients (

White-matter lesion count and volume estimation are key to the diagnosis and monitoring of multiple sclerosis (MS). Automated MS lesion segmentation methods that have been proposed in the past 20 years reach their limits when applied to patients in early disease stages characterized by low lesion load and small lesions. We propose an algorithm to automatically assess MS lesion load (number and volume) while taking into account the mixing of healthy and lesional tissue in the image voxels due to partial volume effects. The proposed method works on 3D MPRAGE and 3D FLAIR images as obtained from current routine MS clinical protocols. The method was evaluated and compared with manual segmentation on a cohort of 39 early-stage MS patients with low disability, and showed higher Dice similarity coefficients (median DSC = 0.55) and higher detection rate (median DR = 61%) than two widely used methods (median DSC = 0.50, median DR

Objectives: In multiple sclerosis (MS), the presence of a paramagnetic rim at the edge of non-gadolinium-enhancing lesions indicates perilesional chronic inflammation. Patients featuring a higher paramagnetic rim lesion burden tend to have more aggressive disease. The objective of this study was to develop and evaluate a convolutional neural network (CNN) architecture (RimNet) for automated detection of paramagnetic rim lesions in MS employing multiple magnetic resonance (MR) imaging contrasts. Materials and methods: Imaging data were acquired at 3 Tesla on three different scanners from two different centers, totaling 124 MS patients, and studied retrospectively. Paramagnetic rim lesion detection was independently assessed by two expert raters on T2*-phase images, yielding 462 rim-positive (rim+) and 4857 rim-negative (rim-) lesions. RimNet was designed using 3D patches centered on candidate lesions in 3D-EPI phase and 3D FLAIR as input to two network branches. The interconnection of branches at both the first network blocks and the last fully connected layers favors the extraction of low and high-level multimodal features, respectively. RimNet’s performance was quantitatively evaluated against experts’ evaluation from both lesion-wise and patient-wise perspectives. For the latter, patients were categorized based on a clinically relevant threshold of 4 rim+ lesions per patient. The individual prediction capabilities of the images were also explored and compared (DeLong test) by testing a CNN trained with one image as input (unimodal). Results: The unimodal exploration showed the superior performance of 3D-EPI phase and 3D-EPI magnitude images in the rim+/- classification task (AUC = 0.913 and 0.901), compared to the 3D FLAIR (AUC = 0.855, Ps

Purpose: The goals of this study were to assess the performance of a novel lesion segmentation tool for longitudinal analyses, as well as to validate the generated lesion progression map between two time points using conventional and non-conventional MR sequences. Material and methods: The lesion segmentation approach was evaluated with (LeMan-PV) and without (LeMan) the partial volume framework using “conventional” and “non-conventional” MR imaging in a two-year follow-up prospective study of 32 early RRMS patients. Manual segmentations of new, enlarged, shrunken, and stable lesions were used to evaluate the performance of the method variants. The true positive rate was estimated for those lesion evolutions in both white matter and cortex. The number of false positives was compared with two strategies for longitudinal analyses. New lesion tissue volume estimation was evaluated using Bland-Altman plots. Wilcoxon signed-rank test was used to evaluate the different setups. Results: The best median of the true positive rate was obtained using LeMan-PV with non-conventional sequences (P

Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously. This situation, and the lack of tools for accurate eye MRI analysis, reduces the interest in MRI beyond the qualitative evaluation of the optic nerve invasion and the confirmation of recurrent malignancies below calcified tumors. In this manuscript, we propose a new framework for the automatic segmentation of eye structures and ocular tumors in multi-sequence MRI. Our key contribution is the introduction of a pathological eye model from which Eye Patient-Specific Features (EPSF) can be computed. These features combine intensity and shape information of pathological tissue while embedded in healthy structures of the eye. We assess our work on a dataset of pathological patient eyes by computing the Dice Similarity Coefficient (DSC) of the sclera, the cornea, the vitreous humor, the lens and the tumor. In addition, we quantitatively show the superior performance of our pathological eye model as compared to the segmentation obtained by using a healthy model (over 4% DSC) and demonstrate the relevance of our EPSF, which improve the final segmentation regardless of the classifier employed.

Ultrasound segmentation is a challenging problem due to the inherent speckle and some artifacts like shadows, attenuation and signal dropout. Existing methods need to include strong priors like shape priors or analytical intensity models to succeed in the segmentation. However, such priors tend to limit these methods to a specific target or imaging settings, and they are not always applicable to pathological cases. This work introduces a semi-supervised segmentation framework for ultrasound imaging that alleviates the limitation of fully automatic segmentation, that is, it is applicable to any kind of target and imaging settings. Our methodology uses a graph of image patches to represent the ultrasound image and user-assisted initialization with labels, which acts as soft priors. The segmentation problem is formulated as a continuous minimum cut problem and solved with an efficient optimization algorithm. We validate our segmentation framework on clinical ultrasound imaging (prostate, fetus, and tumors of the liver and eye). We obtain high similarity agreement with the ground truth provided by medical expert delineations in all applications (94% DICE values in average) and the proposed algorithm performs favorably with the literature.