MS Lesions Research Articles

Phenotyping in vivo chronic inflammation in multiple sclerosis by combined 11C-PBR28 MR-PET and 7T susceptibility-weighted imaging.

11C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists. To investigate the ability of 11C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment. Based on 11C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity. Less than half (44%) of non-PRL WM lesions were active on 11C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores. 11C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume.

Automatic identification of MS lesions based on local steering kernel features and sparse dictionary training

Automatic identification of MS lesions based on local steering kernel features and sparse dictionary training

Impact of insurance status on MRI phenotypes in MS

BackgroundHealth insurance in the United States varies in coverage of essential diagnostic tests, therapies, and specialists. Health disparities between privately and publicly insured patients with MS have not been comprehensively assessed. The objective of this study is to evaluate the impact of public versus private insurance on longitudinal brain outcomes in MS. MethodsLesional, thalamic, and gray and white matter volumes were extracted from longitudinal MRI of 710 MS patients. Baseline volumes and atrophy rates of lesional, thalamic, and gray and white matter volumes were compared across insurance groups. ResultsAfter image quality assessment, 376 (284 private / 92 public), 638 (499 / 139), and 331 (250 / 81), patients were in MS lesion, thalamic, gray and white matter analyses respectively. Baseline lesion volume was higher for publicly insured patients but increased at a slightly higher rate in those privately insured (p = 0.01). Baseline gray matter measurements were lower for patients with public insurance, but thalamic (p < 0.01) and gray matter (p < 0.01) atrophy rates were slightly higher in the private insurance group. ConclusionInsurance type was associated with lesion, thalamic, and gray matter volumes. The results suggest that patients with public insurance may present with more advanced disease.

Effects of disease-modifying therapies on remyelination in multiple sclerosis; evaluation via visual evoked potential test

BackgroundAssessment of the visual pathway, which is frequently affected by MS, provides the opportunity to measure the remyelination of acute and chronic MS lesions in vivo and non-invasively. VEP can be used in this context. Amplitude is a parameter of axonal loss, whereas latency is an in vivo biomarker of myelin repair. This study aimed to evaluate DMT's neuroprotective and pro-remyelinating potential by evaluating VEP latency and amplitude in MS patients. Materials and methodsA total of 74 patients with relapsing MS who had no evidence of optic neuritis were included in the study. Patient data were retrospectively analyzed and recorded. In the VEP test, latency above 118 ms and amplitude below 5.0 μV were considered abnormal. Classified according to DMTs (injectables, teriflunomide, dimethyl fumarate, fingolimod, cladribine, and alemtuzumab). Visual evoked potential tests, clinical features, and cerebrospinal fluid examinations were evaluated by three independent neurologists and one clinical neurophysiologist. ResultsThe mean age at diagnosis was 29.2 ± 9.01, and the mean age at first VEP was 34.97 ± 10.64. In women, latency was lower, and amplitude was higher. The mean differences in latency and amplitude were, respectively, latency prolonged by 0.7 ms on the right and 0.5 ms on the left, and amplitude increased by 0.6 μV on the right and 0.37 μV on the left. However, these changes were not statistically significant. Latency worsening was more prominent in those with longer disease duration (p = 0.011). Those with amplitude or latency worsening had higher EDSS (p = 0.016 and 0.013, respectively). DMTs did not affect these changes. ConclusionProlonged latency is associated with a long disease duration. Deterioration in both amplitude and latency is evident in high EDSS. These results may be an indirect consequence of axonal degeneration dominating remyelination. DMTs do not ameliorate impaired remyelination and neurodegeneration but seem to be sufficient for short-term maintenance of the current state.

Evaluating the complement C1q levels in serum and cerebrospinal fluid in multiple sclerosis patients: Could it serve as a valuable marker in clinical practice?

Immunohistochemical studies have identified complement component C1q in MS lesions. We aimed to compare serum (sC1q) and CSF (csfC1q) levels in a large cohort of MS patients (pwMS) (n = 222) with those of healthy controls (HC, n = 52), individuals with other immune (IND, n = 14), and non-immune neurological disorders (nIND, n = 15), and to analyze their correlation with other biomarkers.pwMS were divided into three series based on their origin. CSF samples were unavailable for HC. All three pwMS cohorts had lower sC1q levels compared to HC and IND. csfC1q was higher in one pwMS cohort, with a trend in another, and correlated with IgG, Free Kappa Light Chains, GFAP, and Chitinase-3 Like Protein-1 in CSF. Our findings suggest a significant role for C1q in MS pathophysiology, potentially serving as a biomarker for disease identification.

Spin-lock based fast whole-brain 3D macromolecular proton fraction mapping of relapsing–remitting multiple sclerosis

A sensitive and efficient imaging technique is required to assess the subtle abnormalities occurring in the normal-appearing white matter (NAWM) and normal-appearing grey matter (NAGM) in patients with relapsing–remitting multiple sclerosis (RRMS). In this study, a fast 3D macromolecular proton fraction (MPF) quantification based on spin-lock (fast MPF-SL) sequence was proposed for brain MPF mapping. Thirty-four participants, including 17 healthy controls and 17 RRMS patients were prospectively recruited. We conducted group comparison and correlation between conventional MPF-SL, fast MPF-SL, and DWI, and compared differences in quantified parameters within MS lesions and the regional NAWM, NAGM, and normal-appearing deep grey matter (NADGN). MPF of MS lesions was significantly reduced (7.17% ± 1.15%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} < 0.01) compared to all corresponding normal-appearing regions. MS patients also showed significantly reduced mean MPF values compared with controls in NAGM (4.87% ± 0.38% vs 5.21% ± 0.32%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.01), NAWM (9.49% ± 0.69% vs 10.32% ± 0.59%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} < 0.01) and NADGM (thalamus 5.59% ± 0.67% vs 6.00% ± 0.41%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.04; caudate 5.10% ± 0.55% vs 5.53% ± 0.58%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.03). MPF and ADC showed abnormalities in otherwise normal appearing close to lesion areas (P < 0.01). In conclusion, time-efficient MPF mapping of the whole brain can be acquired efficiently (< 3 min) using fast MPF-SL. It offers a promising alternative way to detect white matter abnormalities in MS.

Astrocyte-derived factors regulate CNS myelination.

The role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte-derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co-cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked to remyelination deficits following an immune-mediated damage in an EAE mouse model. The observed reduction of brevican expression in reactive astrocytes and human MS lesions suggested a potential link to the compromised remyelination characteristic of neurodegenerative diseases. Our findings suggested brevican's role in myelination may be mediated through interactions with binding partners such as contactin-1 and tenascin-R. Proteomic analysis of resting versus reactive astrocytes highlighted a shift in protein expression profiles, pinpointing candidates that either facilitate or impede CNS repair, suggesting that depending on their reactivity state, astrocytes play a dual role during myelination.

Non-contrast magnetic resonance evaluation of active multiple sclerosis lesions: Emerging role of quantitative synthetic magnetic resonance imaging.

The current study aims to explore the utility of novel synthetic MRI-derived quantitative parameters including myelin-correlated volume (MyC) in identifying active MS lesions without injecting gadolinium contrast. 43 MS patients underwent institutional MS protocol including 3D FLAIR and post-contrast 3D T1VIBE sequence on a 1.5T MR Scanner in addition to synthetic MRI sequence. MS plaques were categorised into enhancing (C) and non-enhancing (N) lesions. They were also sub-categorised based on location into periventricular WM lesions (P), deep WM lesions (D), infratentorial lesions (I) and cortical-juxtacortical (C) lesions. ROIs were placed on Synthetic FLAIR images in MS lesions and quantitative parameters of R1, R2, PD and myelin-correlated volume (MyC) obtained. Sensitivity and specificity for various cut-off values to differentiate enhancing from non-enhancing multiple sclerosis lesions were calculated by performing ROC curve analysis and logistic regression analysis. Contrast enhancing lesions demonstrated significantly higher mean R1, R2 values and lower mean PD values in comparison to non-enhancing lesions (p < 0.05) but with limited specificity. Region-wise analysis revealed high AUC values for mean R1 and R2 at cortical-juxtacortical lesions (p < 0.001) followed by periventricular lesions (p < 0.003) for differentiating enhancing from non-enhancing lesions with no significant contribution from MyC and PD values. Synthetic MRI-derived quantitative parameters of mean R1, R2, MyC and PD hold value in differentiating contrast enhancing and non-enhancing MS lesions without administering gadolinium-based contrast agent. However, the current study did not achieve significant specificity for establishing the same.

BATF2 is a regulator of interferon-γ signaling in astrocytes during neuroinflammation.

Astrocytic interferon (IFN)γ signaling is associated with a reduction in neuroinflammation. We have previously shown that the benefits of astrocytic IFNγ arise from a variety of mechanisms; however, downstream effectors responsible for regulating this protection are unknown. We address this by identifying a specific transcription factor that may play a key role in modulating the consequences of IFNγ signaling. RNA-sequencing of primary human astrocytes treated with IFNγ revealed basic leucine zipper ATF-like transcription factor ( BATF )2 as a highly expressed interferon-specific gene. Primarily studied in the periphery, BATF2 has been shown to exert both inflammatory and protective functions; however, its function in the central nervous system (CNS) is unknown. Here, we demonstrate that human spinal cord astrocytes upregulate BATF2 transcript and protein in an IFNγ-specific manner. Additionally, we found that BATF2 prevents overexpression of interferon regulatory factor (IRF)1 and IRF1 targets such as Caspase-1, which are known downstream pro-inflammatory mediators. We also show that Batf2 -/- mice exhibit exacerbated clinical disease severity in a murine model of CNS autoimmunity, characterized by an increase in both CNS immune cell infiltration and demyelination. Batf2 -/- mice also exhibit increased astrocyte-specific expression of IRF1 and Caspase-1, suggesting an amplified interferon response in vivo . Further, we demonstrate that BATF2 is expressed primarily in astrocytes in MS lesions and that this expression is co-localized with IRF1. Collectively, our results further support a protective role for IFNγ and implicate BATF2 as a key suppressor of overactive immune signaling in astrocytes during neuroinflammation.

Automatic lesion detection at Multiple Sclerosis patients – Comparison of 2D- and 3D-FLAIR-datasets

BackgroundMultiple Sclerosis (MS) is a common autoimmune inflammatory disease of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) allows a sensitive assessment of the CNS and is established for diagnostic, prognostic and (therapy-) monitoring purposes. Especially lesion counting in T2- or Fluid Attenuated Inversion Recovery (FLAIR)-weighted images plays a decisive role in clinical routine. Software-packages allowing an automatic evaluation of image data are increasingly established aiming a faster and improved workflow. These programs allow e.g. the counting, spatial attribution and volumetry of MS-lesions in FLAIR-weighted images. Research has shown that 3D-FLAIR-sequences are superior to 2D-FLAIR-sequences in visual evaluation of lesion burden in MS. An influence on the automatic analysis is expectable but not yet systematically studied. This work will therefore investigate the influence of 2D- and 3D datasets on the results of an automatic assessment. Material and methodsIn this prospective study, 80 Multiple Sclerosis patients underwent a clinically indicated routine MRI examination. The clinical routine protocol already including a 3D-FLAIR sequence was adapted by an additional 2D-FLAIR sequence also conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. To obtain a quantitative analysis for assessment of amount, dissemination and volume of the lesions, the acquired MR images were post-processed using the CE-certified Software mdbrain (mediaire, Berlin, Germany). The resulting data were statistically analysed using the paired t-test for normally distributed data and the Wilcoxon-signed-rank-test for not normally distributed data respectively. Demographic data and data such as the subtype, duration, severity and therapy of the disease were collected, pseudonymized and evaluated. ResultsThere is a significant difference concerning the total number and lesion volume with more lesions being detected (2D: 29.7, +/- 20.22 sd; 3D: 40.1 +/- 31.67 sd; p < 0.0001) but lower total volume (2D: 6.24 +/- 6.11 sd; 3D: 5.39 +/- 6.37 sd; p < 0.0001) when using the 3D- sequence. Especially significantly more small lesions in the unspecific white matter and infratentorial region were detected by using the 3D-FLAIR sequence (p < 0.0001) compared to the 2D-FLAIR image. Main reason for the lower total volume in the 3D-FLAIR sequence was the calculated volume for periventricular lesions which was significantly beneath the calculated volume from the 2D-FLAIR sequence (p < 0.0001). ConclusionAutomatic lesion counting and volumetry is feasible with both 2D- and 3D-weightend FLAIR images. Still, it leads to partly significant differences even between two sequences that both are conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. This study contributes valuable insights into the impact of using different input data from the same patient for automated MS lesion evaluation.

Multiparametric Characterization and Spatial Distribution of Different MS Lesion Phenotypes.

MS lesions exhibit varying degrees of axonal and myelin damage. A comprehensive description of lesion phenotypes could contribute to an improved radiologic evaluation of smoldering inflammation and remyelination processes. This study aimed to identify in vivo distinct MS lesion types using quantitative susceptibility mapping and susceptibility mapping-weighted imaging and to characterize them through T1-relaxometry, myelin mapping, and diffusion MR imaging. The spatial distribution of lesion phenotypes in relation to ventricular CSF was investigated. MS lesions of 53 individuals were categorized into iso- or hypointense lesions, hyperintense lesions, and paramagnetic rim lesions, on the basis of their appearance on quantitative susceptibility mapping alone, according to published criteria, and with the additional support of susceptibility mapping-weighted imaging. Susceptibility values, T1-relaxation times, myelin and free water fractions, intracellular volume fraction, and the orientation dispersion index were compared among lesion phenotypes. The distance of the geometric center of each lesion from the ventricular CSF was calculated. Eight hundred ninety-six MS lesions underwent the categorization process using quantitative susceptibility mapping and susceptibility mapping-weighted imaging. The novel use of susceptibility mapping-weighted images, which revealed additional microvasculature details, led us to re-allocate several lesions to different categories, resulting in a 35.6% decrease in the number of paramagnetic rim lesions, a 22.5% decrease in hyperintense lesions, and a 17.2% increase in iso- or hypointense lesions, with respect to the categorization based on quantitative susceptibility mapping only. The outcome of the categorization based on the joint use of quantitative susceptibility mapping and susceptibility mapping-weighted imaging was that 44.4% of lesions were iso- or hypointense lesions, 47.9% were hyperintense lesions, and 7.7% were paramagnetic rim lesions. A worsening gradient was observed from iso- or hypointense lesions to hyperintense lesions to paramagnetic rim lesions in T1-relaxation times, myelin water fraction, free water fraction, and intracellular volume fraction. Paramagnetic rim lesions were located closer to ventricular CSF than iso- or hypointense lesions. The volume of hyperintense lesions was associated with a more severe disease course. Quantitative susceptibility mapping and susceptibility mapping-weighted imaging allow in vivo classification of MS lesions into different phenotypes, characterized by different levels of axonal and myelin loss and spatial distribution. Hyperintense lesions and paramagnetic rim lesions, which have the most severe microstructural damage, were more often observed in the periventricular WM and were associated with a more severe disease course.

Targeted Therapy of Multiple Sclerosis: A Case for Antigen-Specific Tregs.

Multiple sclerosis is an autoinflammatory condition that results in damage to myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing-remitting disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting potential to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Quantifying chronic lesion expansion in multiple sclerosis: Exploring imaging markers for longitudinal assessment

ObjectivesGradual expansion of multiple sclerosis lesions over time is known to have a significant impact on disease progression. However, accurately quantifying the volume changes in chronic lesions presents challenges due to their slow rate of progression and the need for longitudinal segmentation. Our study addresses this by estimating the expansion of chronic lesions using data collected over a 1–2 year period and exploring imaging markers that do not require longitudinal lesion segmentation. MethodsPre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 42 patients with MS. Lesion expansion, stratified by the severity of tissue damage as measured by mean diffusivity change, was analysed between baseline and 48 months (Progressive Volume/Severity Index, PVSI). Central brain atrophy (CBA) and the degree of tissue loss inside chronic lesions (measured by the change of T1 intensity and mean diffusivity (MD)) were used as surrogate markers. ResultsCBA measured after 2 years of follow-up estimated lesion expansion at 4 years with a high degree of accuracy (r = 0.82, p < 0.001, ROC area under the curve 0.92, sensitivity of 94 %, specificity of 85 %). Increased MD within chronic lesions measured over 2 years was strongly associated with future expansion (r = 0.77, p < 0.001, ROC area under the curve 0.87, sensitivity of 81 % and specificity of 81 %). In contrast, change in lesion T1 hypointensity poorly explained future PVSI (best sensitivity and specificity 60 % and 59 % respectively). InterpretationCBA and, to a lesser extent, the change in MD within chronic MS lesions, measured over a period of 2 years, can provide a reliable and sensitive estimate of the extent and severity of chronic lesion expansion.

Induced saturation transfer recovery steady states (iSTRESS) for proton exchange rate mapping with CEST MRI, a preliminary study

Proton exchange underpins essential mechanisms in diverse MR imaging contrasts. Omega plots have proven effective in mapping proton exchange rates (kex) in live human brains, enabling the differentiation of MS lesion activities and characterization of ischemic stroke. However, Omega plots require extended saturation durations (typically 5 to 10 s), resulting in high specific absorption rates (SAR) that can hinder clinical feasibility. In this study, we introduce a novel kex mapping approach, named induced Saturation Transfer Recovery Steady-States (iSTRESS). iSTRESS integrates an excitation flip angle pulse prior to chemical exchange saturation transfer (CEST) saturation, effectively aligning the magnetization with its steady-state value. This innovation reduces saturation times and mitigates SAR concerns. The formula for iSTRESS-based kex quantification was derived theoretically, involving two measurements with distinct excitation flip angles and saturation B1 values. Bloch-McConnell simulations confirmed that iSTRESS-based kex values closely matched input values (R2 > 0.99). An iSTRESS MRI sequence was implemented on a 9.4 T preclinical MRI, imaging protein phantoms with pH values ranging from 6.2 to 7.4 (n = 4). Z-spectra were acquired using excitation flip angles of 30° and 60°, followed by CEST saturation at powers of 30 and 120 Hz respectively, with a total saturation time of <1 s, resulting in two iSTRESS states for kex mapping. kex maps derived from the phantom study exhibited a linear correlation (R2 > 0.99) with Omega plot results. The developed iSTRESS method allows for kex quantification with significantly reduced saturation times, effectively minimizing SAR concerns.

The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Image harmonization improves consistency of intra-rater delineations of MS lesions in heterogeneous MRI

Clinical magnetic resonance images (MRIs) lack a standard intensity scale due to differences in scanner hardware and the pulse sequences used to acquire the images. When MRIs are used for quantification, as in the evaluation of white matter lesions (WMLs) in multiple sclerosis, this lack of intensity standardization becomes a critical problem affecting both the staging and tracking of the disease and its treatment. This paper presents a study of harmonization on WML segmentation consistency, which is evaluated using an object detection classification scheme that incorporates manual delineations from both the original and harmonized MRIs. A cohort of ten people scanned on two different imaging platforms was studied. An expert rater, blinded to the image source, manually delineated WMLs on images from both scanners before and after harmonization. It was found that there is closer agreement in both global and per-lesion WML volume and spatial distribution after harmonization, demonstrating the importance of image harmonization prior to the creation of manual delineations. These results could lead to better truth models in both the development and evaluation of automated lesion segmentation algorithms.

Age-related decline in cerebral oxygen consumption in multiple sclerosis

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

FractalSpiNet: Fractal-Based U-Net for Automatic Segmentation of Cervical Spinal Cord and MS Lesions in MRI

FractalSpiNet: Fractal-Based U-Net for Automatic Segmentation of Cervical Spinal Cord and MS Lesions in MRI

Detection of Multiple Sclerosis Lesions in Supra- and Infra-Tentorial Anatomical Regions by Double Inversion Recovery, Flair, and T2 MRI Sequences: A Comparative Study in Iraqi Patients

Background: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double-inversion recovery pulse (DIR) pattern was recently proposed to improve the visibility of multiple sclerosis lesions. Objective: To find out how well a DIR sequence, FLAIR, and T2-weighted pulse sequences can find MS lesions in the supratentorial and infratentorial regions. Methods: A total of 37 patients with established diagnoses of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2, and FLAIR sequences. The number of lesions was counted and compared in the three sequences. Results: The DIR sequence detected more infratentorial lesions when compared to the T2 and FLAIR sequences. In the supratentorial region, DIR detected more lesions than T2 and FLAIR. Conclusion: The DIR sequence is highly superior to both the T2 and FLAIR sequences in depicting the lesions, regardless of their anatomical distribution. Moreover, the DIR sequence detected more multiple sclerosis lesions in the infratentorial region than the traditional T2W and FLAIR sequences.

Investigation of an efficient multi-modal convolutional neural network for multiple sclerosis lesion detection

In this study, an automated 2D machine learning approach for fast and precise segmentation of MS lesions from multi-modal magnetic resonance images (mmMRI) is presented. The method is based on an U-Net like convolutional neural network (CNN) for automated 2D slice-based-segmentation of brain MRI volumes. The individual modalities are encoded in separate downsampling branches without weight sharing, to leverage the specific features. Skip connections input feature maps to multi-scale feature fusion (MSFF) blocks at every decoder stage of the network. Those are followed by multi-scale feature upsampling (MSFU) blocks which use the information about lesion shape and location. The CNN is evaluated on two publicly available datasets: The ISBI 2015 longitudinal MS lesion segmentation challenge dataset containing 19 subjects and the MICCAI 2016 MSSEG challenge dataset containing 15 subjects from various scanners. The proposed multi-input 2D architecture is among the top performing approaches in the ISBI challenge, to which open-access papers are available, is able to outperform state-of-the-art 3D approaches without additional post-processing, can be adapted to other scanners quickly, is robust against scanner variability and can be deployed for inference even on a standard laptop without a dedicated GPU.