scholarly journals Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study

2021 ◽  
Vol 12 ◽  
Author(s):  
A. Dal-Bianco ◽  
R. Schranzer ◽  
G. Grabner ◽  
M. Lanzinger ◽  
S. Kolbrink ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
7 Tesla ◽  
Neuropsychological Performance ◽  
Lesion Volume ◽  
Information Processing Speed ◽  
Tissue Destruction ◽  
Subcortical Structures ◽  
Neurofilament Light Chain ◽  
Lateral Ventricles ◽  
Significant Difference

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability.Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed.Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed.Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year.Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

scholarly journals Characterization of thalamic lesions and their correlates in multiple sclerosis by ultra-high-field MRI

2020 ◽  
pp. 135245852093280
Author(s):  
Ambica Mehndiratta ◽  
Constantina A Treaba ◽  
Valeria Barletta ◽  
Elena Herranz ◽  
Russell Ouellette ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Great Majority ◽  
7 Tesla ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Information Processing Speed ◽  
Neurological Disability ◽  
Thalamic Lesions ◽  
Clinical Measures

Background: Thalamic pathology is a marker for neurodegeneration and multiple sclerosis (MS) disease progression. Objective: To characterize (1) the morphology of thalamic lesions, (2) their relation to cortical and white matter (WM) lesions, and (3) clinical measures, and to assess (4) the imaging correlates of thalamic atrophy. Methods: A total of 90 MS patients and 44 healthy controls underwent acquisition of 7 Tesla images for lesion segmentation and 3 Tesla scans for atrophy evaluation. Thalamic lesions were classified according to the shape and the presence of a central venule. Regression analysis identified the predictors of (1) thalamic atrophy, (2) neurological disability, and (3) information processing speed. Results: Thalamic lesions were mostly ovoid than periventricular, and for the great majority (78%) displayed a central venule. Lesion volume in the thalamus, cortex, and WM did not correlate with each other. Thalamic atrophy was only associated with WM lesion volume ( p = 0.002); subpial and WM lesion volumes were associated with neurological disability ( p = 0.016; p < 0.001); and WM and thalamic lesion volumes were related with cognitive impairment ( p < 0.001; p = 0.03). Conclusion: Thalamic lesions are unrelated to those in the cortex and WM, suggesting that they may not share common pathogenic mechanisms and do not contribute to thalamic atrophy. Combined WM, subpial, and thalamic lesion volumes at 7 Tesla contribute to the disease severity.

scholarly journals Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

2021 ◽  
Author(s):  
Hannah L Chandler ◽  
Rachael C Stickland ◽  
Michael Germuska ◽  
Eleonora Patitucci ◽  
Catherine Foster ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oxygen Consumption ◽  
Healthy Volunteers ◽  
Oxygen Supply ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Group Differences ◽  
Lesion Volume ◽  
Brain Physiology ◽  
Significant Difference

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 +/- 6.10 vs. 48.90 +/- 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 +/- 17.31 vs. 136.49 +/- 14.48 μmol/100g/min p<0.001) and DC (2.70 +/- 0.51 vs. 3.18 +/- 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 +/- 0.09 vs. 0.39 +/- 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.

scholarly journals Quantitative Oxygen Extraction Fraction from 7-Tesla MRI Phase: Reproducibility and Application in Multiple Sclerosis

2014 ◽  
Vol 35 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Audrey P Fan ◽  
Sindhuja T Govindarajan ◽  
R Philip Kinkel ◽  
Nancy K Madigan ◽  
A Scott Nielsen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Three Dimensional ◽  
Structural Mri ◽  
Brain Regions ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
7 Tesla ◽  
Information Processing Speed ◽  
Prefrontal Cortical ◽  
Extraction Fraction

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2∗-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ∼10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan—rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls ( P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals

1999 ◽  
Vol 5 (2) ◽  
pp. 74-77 ◽  
Author(s):  
Jennifer C Fulton ◽  
Robert I Grossman ◽  
Lois J Mannon ◽  
Jayaram Udupa ◽  
Dennis L Kolson
Keyword(s):  
Multiple Sclerosis ◽  
Monozygotic Twins ◽  
Subsequent Development ◽  
Monozygotic Twin ◽  
Lesion Volume ◽  
Sibling Pairs ◽  
Clinically Normal ◽  
Volumetric Assessment ◽  
Significant Difference ◽  
Normal Offspring

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.

Lesions by tissue specific imaging characterize multiple sclerosis patients with more advanced disease

2011 ◽  
Vol 17 (12) ◽  
pp. 1424-1431 ◽  
Author(s):  
Francesca Bagnato ◽  
Vasiliki N Ikonomidou ◽  
Peter van Gelderen ◽  
Sungyoung Auh ◽  
Jailan Hanafy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Advanced Disease ◽  
Spin Echo ◽  
Brain Parenchyma ◽  
Lesion Volume ◽  
Tissue Destruction ◽  
Disability Score ◽  
Tissue Specific ◽  
Volumetric Images ◽  
Multiple Sclerosis Patients

Background: Cerebrospinal fluid tissue specific imaging (CSF-TSI), a newly implemented magnetic resonance imaging (MRI) technique, allows visualization of a subset of chronic black holes (cBHs) with MRI characteristics suggestive of the presence of CSF-like fluid, and representing lesions with extensive tissue destruction. Objective: To investigate the relationship between lesions in CSF-TSI and disease measures in patients with multiple sclerosis (MS). Methods: Twenty-six patients with MS were imaged at 3.0 T, obtaining T1-weighted (T1-w) and T2-w spin echo (SE), T1 volumetric images and CSF-TSI images. We measured: (i) lesion volume (LV) in T1-w (cBH-LV) and T2-w SE images, and in CSF-TSI; (ii) brain parenchyma fraction (BPF). Differences between patients with and without CSF-TSI lesions were analyzed and association between clinical and MRI metrics were investigated. Results: cBHs were seen in 92% of the patients while lesions in CSF-TSI were seen in 40%. Patients with CSF-TSI lesions were older, with longer disease duration, higher disability scores, larger cBH-LV and T2-LV, and lower BPF than patients without CSF-TSI lesions (≤0.047). Partial correlation analysis correcting for T2-LV, cBH-LV and BPF showed an association ( p < 0.0001, r = 0.753) between CSF-TSI LV and disability score. Conclusions: CSF-TSI lesions characterize patients with more advanced disease and probably contribute to the progress of disability.

scholarly journals Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

2021 ◽  
Author(s):  
Henning H. Rise ◽  
Synne Brune ◽  
Claudia Chien ◽  
Tone Berge ◽  
Steffan D. Bos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Brain Network ◽  
Axonal Damage ◽  
Base Line ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Random Factor ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

scholarly journals Perivenular brain lesions in a primate multiple sclerosis model at 7-tesla magnetic resonance imaging

2013 ◽  
Vol 20 (1) ◽  
pp. 64-71 ◽  
Author(s):  
María I Gaitán ◽  
Pietro Maggi ◽  
Jillian Wohler ◽  
Emily Leibovitch ◽  
Pascal Sati ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Brain Lesion ◽  
Common Marmoset ◽  
7 Tesla ◽  
Resonance Imaging ◽  
Tissue Destruction ◽  
Lesion Development

Background Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time – a perspective not obtainable with postmortem histopathology. Relapsing–remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter (WM) lesions similar to those observed in MS. Methods Brain lesion development and evolution were studied in vivo and postmortem in four marmosets with EAE through serial T2- and T2*-weighted scans at 7-tesla. Supratentorial WM lesions were identified and characterized. Results Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles. Conclusion As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.

The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo

1998 ◽  
Vol 4 (6) ◽  
pp. 471-474 ◽  
Author(s):  
Massimo Filippi ◽  
Tarek A Yousry ◽  
Maria A Rocca ◽  
Clodoaldo Pereira ◽  
Hatem Alkadhi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cross Talk ◽  
Spin Echo ◽  
Brain Magnetic Resonance Imaging ◽  
Acquisition Time ◽  
Lesion Volume ◽  
Turbo Spin Echo ◽  
Turbo Spin ◽  
Acquisition Scheme ◽  
Significant Difference

We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patient and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3. 1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesion volumes were significantly higher when scheme B was used (P= 0.024). This was due to higher lesion volumes on TSE images (P= 0.006), especially on even-numbered slices (P= 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

Serum neurofilament light chain reflects inflammation-driven neurodegeneration and predicts delayed brain volume loss in early stage of multiple sclerosis

2020 ◽  
Vol 27 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Barbora Srpova ◽  
Tomas Uher ◽  
Tereza Hrnciarova ◽  
Christian Barro ◽  
Michaela Andelova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Light Chain ◽  
Repeated Measures ◽  
Brain Volume ◽  
Lesion Volume ◽  
Volume Loss ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss

Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). Objectives: To investigate the relationship among repeated measures of sNfL, lesion burden accumulation, brain volume loss and clinical measures. Methods: We investigated 172 patients in the early stages of MS (McDonald 2017 criteria). Clinical exams were performed every 3 months and brain magnetic resonance imaging (MRI) scans were collected annually over 48 months. sNfL levels were measured in serum by Simoa assay at the time of treatment initiation and then annually over 36 months. Results: In repeated-measures analysis, considering all time points, we found a strong relationship between percentage changes of sNfL and lesion burden accumulation assessed by T1 lesion volume ( p < 0.001) and T2 lesion number ( p < 0.001). There was no relationship between percentage changes of sNfL and brain volume loss over 36 months ( p > 0.1). Early sNfL levels were associated with delayed brain volume loss after 48 months ( p < 0.001). Patients with No Evidence of Disease Activity (NEDA-3) status showed lower sNfL levels compared with active MS patients. Conclusions: sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.

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