MS Lesions Research Articles

Accuracy of Noncontrast T2 SPACE in Active MS Cord Lesion Detection.

The diagnosis of active MS lesions is often based on postgadolinium T1-weighted MR imaging. Recent studies suggest a risk of IV gadolinium to patients, predominantly based on gadolinium deposition in tissue. Noncontrast sequences have shown promise in MS diagnosis, but none differentiate acute from chronic MS lesions. We hypothesized that 3D T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) MR imaging can help detect and differentiate active-versus-chronic MS lesions without the need for IV contrast. In this single-center retrospective study, 340 spinal MR imaging cases of MS were collected in a 24-month period. Two senior neuroradiologists blindly and independently reviewed postcontrast T1-weighted sagittal and T2-SPACE sagittal images for the presence of MS lesions, associated cord expansion/atrophy on T2-SPACE, and enhancement on postcontrast T1WI. Discrepancies were resolved by consensus between the readers. Sensitivity, specificity, and accuracy of T2-SPACE compared with postcontrast T1WI were computed, and interobserver agreement was calculated. The sensitivity of lesion detection on T2-SPACE was 85.71%, 95% CI, 63.66%-96.95%; with a specificity of 93.52%, 95% CI, 90.06%-96.05%; and an accuracy of 92.99%, 95% CI, 89.58%-95.56. Additionally, 16/21 (84.2%) acute enhancing cord lesions showed cord expansion on T2-SPACE. The interobserver agreement was 92%. Our study shows that T2-SPACE facilitates noncontrast detection of acute MS lesions with high accuracy compared with postcontrast T1WI and with high interobserver agreement. The lack of gadolinium use provides an advantage, bypassing any potential adverse effects of repetitive contrast administration.

Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis

BackgroundMultiple sclerosis (MS) is an immune-mediated neurological disorder, and up to 50% of patients experience depression. We investigated how white matter network disruption is related to depression in MS. MethodsUsing electronic health records, 380 participants with MS were identified. Depressed individuals (MS+Depression group; n = 232) included persons who had an ICD-10 depression diagnosis, had a prescription for antidepressant medication, or screened positive via Patient Health Questionnaire (PHQ)-2 or PHQ-9. Age- and sex-matched nondepressed individuals with MS (MS−Depression group; n = 148) included persons who had no prior depression diagnosis, had no psychiatric medication prescriptions, and were asymptomatic on PHQ-2 or PHQ-9. Research-quality 3T structural magnetic resonance imaging was obtained as part of routine care. We first evaluated whether lesions were preferentially located within the depression network compared with other brain regions. Next, we examined if MS+Depression patients had greater lesion burden and if this was driven by lesions in the depression network. Primary outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. ResultsMS lesions preferentially affected fascicles within versus outside the depression network (β = 0.09, 95% CI = 0.08 to 0.10, p < .001). MS+Depression patients had more lesion burden (β = 0.06, 95% CI = 0.01 to 0.10, p = .015); this was driven by lesions within the depression network (β = 0.02, 95% CI = 0.003 to 0.040, p = .020). ConclusionsWe demonstrated that lesion location and burden may contribute to depression comorbidity in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression patients had more disease than MS−Depression patients, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Association between limbic system lesions and anxiety in persons with multiple sclerosis

BackgroundPersons with Multiple Sclerosis (PwMS) have a higher rate of anxiety and depression than the general population. Depression has been associated with clinical relapses; temporal lesions were shown to predict depression severity. Anxiety is considerably understudied. The role of MS lesions in the limbic system is also understudied, partly due to difficulties identifying limbic lesions on standard 1.5 and 3 Tesla MRI. MethodsThis is a retrospective study of 23 PwMS who underwent 7T MRI on the same day as completing the Hospital Anxiety and Depression Scale (HADS). MRI was performed on a Siemens 7T MRI Plus and an 8-channel transmit coil with 32 receiver channels operating in pTx mode. MP2RAGE and DIR-SPACE sequences were analyzed to determine the number of lesions within the limbic system. ResultsThe median number of lesions in the limbic system was 2.0 (range 0–7). When comparing the presence or absence of lesions in the limbic system, there was a significant relationship with anxiety (X2 (1, N = 23)=4.44, p = 0.035), but not for depression. ConclusionAlthough only a small sample size, this study provides preliminary evidence that lesions in the limbic system are associated with the presence of anxiety in PwMS. This relationship warrants further investigation.

Pseudocystic inflammatory demyelinating lesions in multiple sclerosis: A clinical, radiological, and pathological description.

Pseudocystic inflammatory demyelinating lesions (PIDLs) are poorly described in MS and might represent a diagnostic challenge. We described the clinical, radiological, pathological, and follow-up characteristics of 13 PIDL in 9 MS patients. We constituted a single-center retrospective case series of PIDLs in MS, defined on MRI as expansive cyst-like lesions, with a fluid-signal content, and a diameter of 1 cm or more. PIDL often occurred at first event (56%), were often asymptomatic (69%), and encircled by a hypo-T2 diffusion-restricted rim and a thin ring-like gadolinium enhancement (100%) on magnetic resonance imaging (MRI). Associated typical MS lesions were constant. Biopsies from two PIDLs displayed classical features of active MS, except for unusual edema. PIDLs are clinically unremarkable and associated with a good outcome. Their easily recognizable MRI features could help avoid biopsy.

Mechanisms of metabolic stress induced cell death of human oligodendrocytes: relevance for progressive multiple sclerosis

Oligodendrocyte (OL) injury and loss are central features of evolving lesions in multiple sclerosis. Potential causative mechanisms of OL loss include metabolic stress within the lesion microenvironment. Here we use the injury response of primary human OLs (hOLs) to metabolic stress (reduced glucose/nutrients) in vitro to help define the basis for the in situ features of OLs in cases of MS. Under metabolic stress in vitro, we detected reduction in ATP levels per cell that precede changes in survival. Autophagy was initially activated, although ATP levels were not altered by inhibitors (chloroquine) or activators (Torin-1). Prolonged stress resulted in autophagy failure, documented by non-fusion of autophagosomes and lysosomes. Consistent with our in vitro results, we detected higher expression of LC3, a marker of autophagosomes in OLs, in MS lesions compared to controls. Both in vitro and in situ, we observe a reduction in nuclear size of remaining OLs. Prolonged stress resulted in increased ROS and cleavage of spectrin, a target of Ca2+-dependent proteases. Cell death was however not prevented by inhibitors of ferroptosis or MPT-driven necrosis, the regulated cell death (RCD) pathways most likely to be activated by metabolic stress. hOLs have decreased expression of VDAC1, VDAC2, and of genes regulating iron accumulation and cyclophilin. RNA sequencing analyses did not identify activation of these RCD pathways in vitro or in MS cases. We conclude that this distinct response of hOLs, including resistance to RCD, reflects the combined impact of autophagy failure, increased ROS, and calcium influx, resulting in metabolic collapse and degeneration of cellular structural integrity. Defining the basis of OL injury and death provides guidance for development of neuro-protective strategies.

Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Scanner agnostic large-scale evaluation of MS lesion delineation tool for clinical MRI.

Patients with MS are MRI scanned continuously throughout their disease course resulting in a large manual workload for radiologists which includes lesion detection and size estimation. Though many models for automatic lesion segmentation have been published, few are used broadly in clinic today, as there is a lack of testing on clinical datasets. By collecting a large, heterogeneous training dataset directly from our MS clinic we aim to present a model which is robust to different scanner protocols and artefacts and which only uses MRI modalities present in routine clinical examinations. We retrospectively included 746 patients from routine examinations at our MS clinic. The inclusion criteria included acquisition at one of seven different scanners and an MRI protocol including 2D or 3D T2-w FLAIR, T2-w and T1-w images. Reference lesion masks on the training (n = 571) and validation (n = 70) datasets were generated using a preliminary segmentation model and subsequent manual correction. The test dataset (n = 100) was manually delineated. Our segmentation model https://github.com/CAAI/AIMS/ was based on the popular nnU-Net, which has won several biomedical segmentation challenges. We tested our model against the published segmentation models HD-MS-Lesions, which is also based on nnU-Net, trained with a more homogenous patient cohort. We furthermore tested model robustness to data from unseen scanners by performing a leave-one-scanner-out experiment. We found that our model was able to segment MS white matter lesions with a performance comparable to literature: DSC = 0.68, precision = 0.90, recall = 0.70, f1 = 0.78. Furthermore, the model outperformed HD-MS-Lesions in all metrics except precision = 0.96. In the leave-one-scanner-out experiment there was no significant change in performance (p < 0.05) between any of the models which were only trained on part of the dataset and the full segmentation model. In conclusion we have seen, that by including a large, heterogeneous dataset emulating clinical reality, we have trained a segmentation model which maintains a high segmentation performance while being robust to data from unseen scanners. This broadens the applicability of the model in clinic and paves the way for clinical implementation.

Evaluation of the Statistical Detection of Change Algorithm for Screening Patients with MS with New Lesion Activity on Longitudinal Brain MRI.

Identification of new MS lesions on longitudinal MR imaging by human readers is time-consuming and prone to error. Our objective was to evaluate the improvement in the performance of subject-level detection by readers when assisted by the automated statistical detection of change algorithm. A total of 200 patients with MS with a mean interscan interval of 13.2 (SD, 2.4) months were included. Statistical detection of change was applied to the baseline and follow-up FLAIR images to detect potential new lesions for confirmation by readers (Reader + statistical detection of change method). This method was compared with readers operating in the clinical workflow (Reader method) for a subject-level detection of new lesions. Reader + statistical detection of change found 30 subjects (15.0%) with at least 1 new lesion, while Reader detected 16 subjects (8.0%). As a subject-level screening tool, statistical detection of change achieved a perfect sensitivity of 1.00 (95% CI, 0.88-1.00) and a moderate specificity of 0.67 (95% CI, 0.59-0.74). The agreement on a subject level was 0.91 (95% CI, 0.87-0.95) between Reader + statistical detection of change and Reader, and 0.72 (95% CI, 0.66-0.78) between Reader + statistical detection of change and statistical detection of change. The statistical detection of change algorithm can serve as a time-saving screening tool to assist human readers in verifying 3D FLAIR images of patients with MS with suspected new lesions. Our promising results warrant further evaluation of statistical detection of change in prospective multireader clinical studies.

Metabolomic Profiling of Multiple Sclerosis Lesions and Periplaque White Matter Demonstrates Extensive Changes in Lipid Metabolism (P2-3.010)

<h3>Objective:</h3> To identify whether there are differences between the brain tissue metabolome in people with multiple sclerosis (PwMS) compared to controls and between the different type of MS lesions <h3>Background:</h3> MS is characterized by immune-mediated white matter (WM) demyelination and consecutive axonal loss. Whether this process alters the metabolome in the affected brain areas is not clear. <h3>Design/Methods:</h3> Brain tissues, obtained from 5 PwMS and 12 controls, were sent for metabolomic analysis. In PwMS, tissues were extracted from the edge and core of demyelinated WM chronic active and inactive lesions, and periplaque WM, while in controls they were dissected from normal WM. Weighted gene correlation network analysis (WGCNA) were utilized to cluster highly correlated metabolites together into modules. We then applied generalized estimating equations models to compare WGCNA-module scores between different tissues, accounting for multiple metabolomic profiles contributed by some subjects. <h3>Results:</h3> MS lesions were found to have decreased concentrations of hexosylceramides (p = 0.019), glycero-phospholipids (p = 3.6E−7), nucleotide metabolites (p = 5.0E−4), and long-chain fatty acids (p = 1.6E−6) and increased concentrations of dipeptides/sugars (p = 0.0063), sphingosines (p = 0.0026), phospholipids (p = 0.0019), sphingomyelines and ceramides (p = 4.4E−10) compared to control WM. In MS periplaques there were decreased levels of glycerol-phospholipids (p = 0.017) and long-chain fatty acids (p = 0.014) and increased levels of sphingomyelines and ceramides (p = 0.0026) compared to control WM. <h3>Conclusions:</h3> Myelin lipids were significantly altered in MS with more prominent differences in lesions, and these could potentially act as biomarkers of inflammation and neurodegeneration in PwMS. <b>Disclosure:</b> Dr. Ladakis has nothing to disclose. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. The institution of Dr. Absinta has received research support from International MS Alliance. The institution of Dr. Absinta has received research support from FRRB Early Career Award. The institution of Dr. Absinta has received research support from Cariplo Foundation. Dr. Reyes-Mantilla has nothing to disclose. The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research . The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

Trial of Tauroursodeoxycholic Acid Supplementation in Patients with Progressive MS (S16.007)

<h3>Objective:</h3> The main aim of this trial was to assess safety and tolerability of tauroursodeoxycholic acid (TUDCA) supplementation in patients with progressive multiple sclerosis (pwPMS). Secondary objectives were to assess the effects on serum BA profile and clinical outcomes. <h3>Background:</h3> We have previously identified changes in the metabolome, specifically in bile acid (BA) metabolism in MS. We demonstrated that BA receptors are present in MS lesions, and TUDCA supplementation ameliorated disease in an animal model of MS and had direct anti-inflammatory effects on astrocytes and microglia. Trials in other neurodegenerative diseases have shown that TUDCA may be neuroprotective. The effects of TUDCA supplementation on MS are unknown but could provide a pathway for developing new therapies in PMS. <h3>Design/Methods:</h3> In this randomized, double-blinded trial, pwPMS were enrolled and randomized 1:1 to either receive TUDCA (1 g twice daily) or placebo for 16 weeks. Clinical visits occurred at 0, 8, and 16 weeks. Primary outcomes were safety and tolerability of TUDCA. Secondary outcomes included changes in BA serum levels and clinical outcomes. <h3>Results:</h3> Of the 59 participants enrolled, 47 (80%) completed ≥2 visits and were included in the analysis (21 in placebo arm, 26 in TUDCA arm). The number of participants reporting adverse events was not significantly different between groups (10 in TUDCA arm vs 7 in placebo arm; p=0.72). The TUDCA group demonstrated significant increases over time in levels of TUDCA (p&lt;0.001), glycoursodeoxycholic acid (p&lt;0.001), ursodeoxycholic acid (p&lt;0.001), and lithocholic acid (p=0.02). There was a significant improvement in MSFC (p=0.03), while no change was noted in EDSS and MSQOL-54 mental or physical composites in the TUDCA arm; no significant changes were noted in these outcomes in the placebo arm. <h3>Conclusions:</h3> TUDCA supplementation was safe and tolerable in pwPMS, and led to significant increases in levels of several bioactive secondary BAs and improvement in MSFC score. <b>Disclosure:</b> The institution of Dr. Harrison has received research support from National MS Society. Dr. Ladakis has nothing to disclose. Mr. Hwang has nothing to disclose. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Sotirchos has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Sotirchos has received research support from National Institutes of Health. The institution of Dr. Sotirchos has received research support from National Multiple Sclerosis Society. The institution of Dr. Sotirchos has received research support from Sumaira Foundation. The institution of Dr. Sotirchos has received research support from Genentech. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Ad Hoc Reviewer with National Institutes of Health. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Disarm Therapeutics. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Investigation. The institution of Dr. Calabresi has received research support from Biogen. The institution of Dr. Calabresi has received research support from Annexon. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME. Dr. Calabresi has a non-compensated relationship as a Consultant with Apellis that is relevant to AAN interests or activities. The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis

Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). Objective: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. Methods: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. Results: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. Conclusions: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. Trial Registration: AFFINITY [NCT03222973].

Get With the Guidelines on MS Imaging by Leveraging Peer Learning

To achieve consensus on the performance, interpretation and reporting of MS imaging according to up-to-date guidelines using the Peer Learning Methodology. We utilized the Peer Learning Methodology to engage our clinical and radiology colleagues, review the current guidelines, acheive consensus on imaging techniques and reporting standards. After implementing changes, we collected radiologist feedback on the impact of the optimized images on their interpretation. Survey responders indicated a strong preference for the new protocol in terms of overall image quality, individual lesions conspicuity and confidence in the ability to detect an MS lesion. The new protocol was preferred for both MS diagnosis and MS surveillance in 25 of 28 responses. The Peer Learning Methodology is an effective tool to standardize and improve MR imaging quality, interpretation and reporting for Multiple Sclerosis in accordance with current guidelines.

Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

Objectives: We investigated choroid plexus (CP) volume in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established relapsing–remitting multiple sclerosis (RRMS) and healthy controls (HCs). Methods: Three-dimensional (3D) T1, T2-FLAIR and diffusion-weighted sequences were acquired from 44 ON CIS patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 HCs were also included for comparison. Results: CP volumes was larger in both ON CIS and RRMS groups compared to HCs, but not significantly different between ON CIS and RRMS patients (analysis of covariance (ANCOVA) adjusted for multiple comparisons). Twenty-three ON CIS patients who converted to clinically definite MS (MS) demonstrated CP volume similar to RRMS patients, but significantly larger compared to HCs. In this sub-group, CP volume was not associated with the severity of optic nerve inflammation or long-term axonal loss, not with brain lesion load. A transient increase of CP volume was observed following an occurrence of new MS lesions on brain magnetic resonance imaging (MRI). Interpretation: Enlarged CP can be observed very early in a disease. It transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.

Fully Automatic Method for Reliable Spinal Cord Compartment Segmentation in Multiple Sclerosis.

Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.

Denoising of diffusion MRI in the cervical spinal cord – effects of denoising strategy and acquisition on intra-cord contrast, signal modeling, and feature conspicuity

Quantitative diffusion MRI (dMRI) is a promising technique for evaluating the spinal cord in health and disease. However, low signal-to-noise ratio (SNR) can impede interpretation and quantification of these images. The purpose of this study is to evaluate several dMRI denoising approaches on their ability to improve the quality, reliability, and accuracy of quantitative diffusion MRI of the spinal cord. We evaluate three denoising approaches (Non-Local Means, Marchenko-Pastur PCA, and a newly proposed Patch2Self algorithm) and conduct five experiments to validate the denoising performance on clinical-quality and commonly-acquired dMRI acquisitions: 1) a phantom experiment to assess denoising error and bias; 2) a multi-vendor, multi-acquisition open experiment for both qualitative and quantitative evaluation of noise residuals; 3) a bootstrapping experiment to estimate uncertainty of parametric maps; 4) an assessment of spinal cord lesion conspicuity in a multiple sclerosis group; and 5) an evaluation of denoising for advanced parametric multi-compartment modeling. We find that all methods improve signal-to-noise ratio and conspicuity of MS lesions in individual diffusion weighted images (DWIs), but MPPCA and Patch2Self excel at improving the quality and intra-cord contrast of diffusion weighted images – removing signal fluctuations due to thermal noise while improving precision of estimation of diffusion parameters even with very few DWIs (i.e., 16-32) typical of clinical acquisitions. These denoising approaches hold promise for facilitating reliable diffusion observations and measurements in the spinal cord to investigate biological and pathological processes.

Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis

Background: Magnetic resonance imaging (MRI) markers for chronic active lesions in MS include slowly expanding lesions (SELs) and paramagnetic rim lesions (PRLs). Objectives: To identify the relationship between SELs and PRLs in MS, and their association with disability. Methods: 61 people with MS (pwMS) followed retrospectively with MRI including baseline susceptibility-weighted imaging, and longitudinal T1 and T2-weighted scans. SELs were computed using deformation field maps; PRLs were visually identified. Mixed-effects models assessed differences in Expanded Disability Status Scale (EDSS) score changes between the group defined by the presence of SELs and or PRLs. Results: The median follow-up time was 3.2 years. At baseline, out of 1492 lesions, 616 were classified as SELs, and 80 as PRLs. 92% of patients had ⩾ 1 SEL, 56% had ⩾ 1 PRL, while both were found in 51%. SELs compared to non-SELs were more likely to also be PRLs (7% vs. 4%, p = 0.027). PRL counts positively correlated with SEL counts (ρ= 0.28, p = 0.03). SEL + PRL + patients had greater increases in EDSS over time (beta = 0.15/year, 95% confidence interval (0.04, 0.27), p = 0.009) than SEL+PRL-patients. Conclusion: SELs are more numerous than PRLs in pwMS. Compared with either SELs or PRLs found in isolation, their joint occurrence was associated with greater clinical progression.

Role of MR in Evaluating Multiple Sclerosis

Introduction: Multiple sclerosis is an inflammatory disease that attacks the central nervous system CNS (brain and spinal cord). Specifically, it attacks the myeline sheath of the neuron cells (1-3). Up to now there is no known pathophysiological cause of the MS disease but it is believed to be autoimmune. Autoimmune means the immunity system attacks normal tissues without obvious cause. It results in progressive neurological deficits leading to accumulating disabilities. The wide distribution of plaques (name of MS lesion) produces a variety of clinical symptoms. Key words: Multiple sclerosis, evaluation, MRI

Automated segmentation of multiple sclerosis lesions based on convolutional neural networks

ABSTRACT Automatic segmentation using Deep Learning (DL) has recently outperformed previous methods. In this paper, we are interested in automatic MS lesion segmentation of 2D images using DL approaches. The main challenge is to propose a new model that uses referenced CNN models such as U-Net, ResNet, and DenseNet, but with less parameters and a faster execution time. We evaluated the performance of our suggested technique, ‘Concat-U-Net’, to that of three implemented models, using two different datasets: our private MS database and the public ISBI. A comparison research was conducted using the Dice, Sensitivity, Precision, and PR-Curve evaluation metrics. On our private data set, the best Dice produced by the suggested technique was 0.80 as well as 0.77, 0.98, and 0.78 for sensitivity, PR-curve, and Precision, respectively. We enhanced MS segmentation results using the ISBI database and acquired a Dice value of 0.72, which is close to the results reported in the literature. For our data set and ISBI database, we lowered the elapsed execution time from 16.99 s to 9.36 s and from 25.02 s to 4.37 s, respectively. Furthermore, by reducing the number of parameters, we achieved an 81.51% time gain.

Myelin-weighted imaging derived from quantitative parameter mapping

PurposeWe developed a novel method which is applicable to visualize contrast according to myelin components in the human brain using relaxation time derived from quantitative parameter mapping magnetic resonance imaging (QPM-MRI). Materials and methodsUsing healthy volunteer data (n = 10), we verified that our method demonstrated that the myelin-weighted contrast increased proportionally by products R1 and R2*, i.e., QPM-myelin-weighted image, in which modified T1-weighted/T2-weighted (T1w/T2w) ratio mapping method was applied. We compared measurement values in white matter (WM) and gray matter (GM) regions of the T1w/T2w ratio and R1·R2* product maps of healthy volunteers. Linear regression analysis between each value. Mann Whitney U test between WM and GM signals in each myelin map. In addition, Additionally, QPM-myelin-weighted image was applied to a 32-year-old female MS patient. ResultsLinear regression analysis showed a highly significant correlation between conventional T1w/T2w ratios and R1·R2* products derived from QPM (R = 0.73, P < 0.0001). Moreover, there is a significant difference between WM and GM structures in each myelin images (both, P < 0.0001). Additionally, in a clinical case, MS lesions enabled observation of not only MS plaques but also heterogeneous myelin signal loss associated with demyelination more clearly than T2w image and conventional T1w/T2w ratio image. ConclusionOur myelin-weighted imaging technique using QPM may be useful for myelin visualization and is expected to become independent of measurement conditions due to having quantitative characteristics of QPM itself.

Image registration and appearance adaptation in non-correspondent image regions for new MS lesions detection.

Manual detection of newly formed lesions in multiple sclerosis is an important but tedious and difficult task. Several approaches for automating the detection of new lesions have recently been proposed, but they tend to either overestimate the actual amount of new lesions or to miss many lesions. In this paper, an image registration convolutional neural network (CNN) that adapts the baseline image to the follow-up image by spatial deformations and simulation of new lesions is proposed. Simultaneously, segmentations of new lesions are generated, which are shown to reliably estimate the real new lesion load and to separate stable and progressive patients. Several applications of the proposed network emerge: image registration, detection and segmentation of new lesions, and modeling of new MS lesions. The modeled lesions offer the possibility to investigate the intensity profile of new lesions.