scholarly journals Optimal indicator for histogram analysis of fractional anisotropy for normal-appearing white matter in multiple sclerosis

2021 ◽  
Vol 26 (4) ◽  
pp. 785-793
Author(s):  
Kimihiro Ogisu ◽  
Masaaki Niino ◽  
Yusei Miyazaki ◽  
Seiji Kikuchi
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Single Shot ◽  
Healthy Controls ◽  
Planar Imaging ◽  
Diffusion Weighted Images ◽  
Normal Appearing White Matter ◽  
Imaging Sequence ◽  
Scale Scores

Background: Normal-appearing white matter (NAWM) lesions are known to be present in multiple sclerosis (MS); however, it is not easy to distinguish these lesions from others in MRI. This study aimed to investigate the most useful value for estimating NAWM damage using fractional anisotropy (FA) histograms analysis. Methods: Data from patients with relapsing-remitting MS and healthy controls were analyzed using a 1.5T MRI system with SENSE-Head-8 coil. FA maps with diffusion- weighted images were acquired using a single-shot echo-planar imaging sequence. The median, standard deviation (SD), kurtosis, and skewness of white matter (WM) of each subject were compared between MS and healthy controls using an in-house application. Results: FA decrease in 8 patients with MS was observed upon comparison with 12 controls and leaned toward the left side. While the SDs of the healthy controls were not significantly different from those of patients with MS, patients with MS expressed significantly lower median values, and higher kurtosis and skewness compared to healthy controls. A trend for inverse associations existed between median and expanded disability status scale scores. Conclusion: Our data suggests that median FA values can allow for distinguishing between patients with MS and healthy controls with high accuracy.

scholarly journals Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Kasper Winther Andersen ◽  
Samo Lasič ◽  
Henrik Lundell ◽  
Markus Nilsson ◽  
Daniel Topgaard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Mri ◽  
Fibre Orientation ◽  
Cerebral White Matter ◽  
Healthy Controls ◽  
Lesion Load ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting

Abstract Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres. This complicates the detection of disease-related damage in large parts of cerebral white matter where microstructure physiologically displays a high degree of fibre dispersion. To resolve this ambiguity, we employed a novel tensor-valued encoding method for diffusion MRI, which yields a microscopic fractional anisotropy metric that is unaffected by regional variations in orientation dispersion. In 26 patients with relapsing-remitting multiple sclerosis, 14 patients with primary-progressive multiple sclerosis and 27 age-matched healthy controls, we compared standard fractional anisotropy mapping with the novel microscopic fractional anisotropy mapping method, focusing on normal-appearing white matter. Mean microscopic fractional anisotropy and standard fractional anisotropy of normal-appearing white matter were significantly reduced in both patient groups relative to healthy controls, but microscopic fractional anisotropy yielded a better reflection of disease-related white-matter alterations. The reduction in mean microscopic fractional anisotropy showed a significant positive linear relationship with physical disability, as reflected by the expanded disability status scale. Mean reduction of microscopic fractional anisotropy in normal-appearing white matter also scaled positively with individual cognitive dysfunction, as measured with the symbol digit modality test. Mean microscopic fractional anisotropy reduction in normal-appearing white matter also showed a positive relationship with total white-matter lesion load as well as lesion load in specific tract systems. None of these relationships between normal-appearing white-matter microstructure and clinical, cognitive or structural measures emerged when using mean fractional anisotropy. Together, the results provide converging evidence that microscopic fractional anisotropy mapping substantially advances the assessment of cerebral white matter in multiple sclerosis by disentangling microstructure damage from variations in physiological fibre orientation dispersion at the stage of data acquisition. Since tensor-valued encoding can be implemented in routine diffusion MRI, microscopic fractional anisotropy mapping bears considerable potential for the future assessment of disease progression in normal-appearing white matter in both relapsing-remitting and progressive forms of multiple sclerosis as well as other white-matter-related brain diseases.

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis

Brain ◽  
2020 ◽  
Author(s):  
Simona Schiavi ◽  
Maria Petracca ◽  
Peng Sun ◽  
Lazar Fleysher ◽  
Sirio Cocozza ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
White Matter ◽  
Corpus Callosum ◽  
Fractional Anisotropy ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Spectrum Imaging

Abstract The aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) were measured from whole brain white matter lesions and from both lesions and normal appearing white matter of the corpus callosum. Significant differences were found between T1-isointense and black holes (P ranging from 0.005 to <0.001) and between lesions’ centre and rim (P < 0.001) for all the metrics. When comparing the three subject groups in terms of metrics derived from corpus callosum normal appearing white matter and T2-hyperintense lesions, a significant difference was found between healthy controls and relapsing-remitting patients for all metrics except restricted fraction and fractional anisotropy; between healthy controls and progressive patients for all metrics except restricted fraction and between relapsing-remitting and progressive multiple sclerosis patients for all metrics except fibres and restricted fractions (P ranging from 0.05 to <0.001 for all). Significant associations were found between corpus callosum normal-appearing white matter fibres fraction/non-restricted fraction and the Symbol Digit Modality Test (respectively, r = 0.35, P = 0.043; r = −0.35, P = 0.046), and between black holes radial diffusivity and Expanded Disability Status Score (r = 0.59, P = 0.002). We showed the feasibility of diffusion basis spectrum imaging metrics at 7 T, confirmed the role of the derived metrics in the characterization of lesions and normal appearing white matter tissue in different stages of the disease and demonstrated their clinical relevance. Thus, suggesting that diffusion basis spectrum imaging is a promising tool to investigate multiple sclerosis pathophysiology, monitor disease progression and treatment response.

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology

Brain ◽  
2020 ◽  
Author(s):  
Ermelinda De Meo ◽  
Loredana Storelli ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Paediatric Multiple Sclerosis ◽  
Multiple Sclerosis Patients

Abstract The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics—including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio—in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183–0.369; P range = 0.010–0.046), while we found significant mean diffusivity (f2 range = 0.101–0.369; P range = 0.018–0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = −0.27–0.34; P range = 0.004–0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24–0.27; P range = 0.006–0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

Mapping white matter damage distribution in neuromyelitis optica spectrum disorders with a multimodal MRI approach

2020 ◽  
pp. 135245852094149
Author(s):  
Laura Cacciaguerra ◽  
Maria A Rocca ◽  
Loredana Storelli ◽  
Marta Radaelli ◽  
Massimo Filippi
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Neuromyelitis Optica ◽  
Mean Diffusivity ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
White Matter Damage ◽  
Axial Diffusivity ◽  
Spectrum Disorders

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p < 0.001), radial ( p < 0.001–0.004), and axial diffusivity ( p = 0.002–0.008) and preserved T1/T2-weighted ratio in all bands. Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

scholarly journals A Quantitative Study of Water Diffusion in Multiple Sclerosis Lesions and Normal-Appearing White Matter Using Echo-Planar Imaging

2000 ◽  
Vol 57 (7) ◽  
pp. 1017 ◽  
Author(s):  
Massimo Filippi ◽  
Giuseppe Iannucci ◽  
Mara Cercignani ◽  
Maria Assunta Rocca ◽  
Arianna Pratesi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Quantitative Study ◽  
Echo Planar Imaging ◽  
Water Diffusion ◽  
Planar Imaging ◽  
Normal Appearing White Matter ◽  
Echo Planar

scholarly journals [18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis

2019 ◽  
Vol 47 (2) ◽  
pp. 366-378 ◽  
Author(s):  
Antonio Carotenuto ◽  
Beniamino Giordano ◽  
George Dervenoulas ◽  
Heather Wilson ◽  
Mattia Veronese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Mr Imaging ◽  
Pet Imaging ◽  
Diffusion Tensor ◽  
Volume Ratio ◽  
Reference Method ◽  
Healthy Controls ◽  
Normal Appearing White Matter

Abstract Purpose We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [18F]florbetapir PET-MR imaging. Methods We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [18F]florbetapir PET-MR and both a clinical and cognitive assessment. [18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70–90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling. Results [18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV70–90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26). Conclusion Our findings demonstrate that [18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

scholarly journals CBMT-26. SERIAL CHARACTERIZATION OF HYPERPOLARIZED [1-13C]PYRUVATE METABOLISM IN PATIENTS WITH GLIOMA AND THE INFLUENCE OF BEVACIZUMAB

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi38-vi39
Author(s):  
Adam Autry ◽  
Jeremy Gordon ◽  
Hsin-Yu Chen ◽  
Marisa Lafontaine ◽  
Javier Villanueva-Meyer ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Disease Recurrence ◽  
Healthy Controls ◽  
Planar Imaging ◽  
Non Invasive ◽  
Normal Appearing White Matter ◽  
Imaging Sequence ◽  
Mri Scans ◽  
Standard Of Care Treatment ◽  
Echo Planar

Abstract Treatment-related changes often mimic or mask tumor on standard anatomic imaging, making it difficult to monitor disease recurrence. Hyperpolarized (HP) carbon-13 MR imaging allows for real-time non-invasive measurement of metabolism, which may improve patient surveillance. Here, we focused on characterizing serial HP scans in patients undergoing treatment compared to healthy controls. Serial dynamic HP C-13 MRI scans were performed on 5 patients with recurrent glioma (22 total) and 3 healthy controls (4 total) using an echo-planar imaging sequence (2.88-8cm3 spatial resolution, 3s temporal resolution, 60s), following injection of 0.43mL/kg of 250mM HP [1-13C]pyruvate. Apparent rate constants were modeled for enzymatic conversion of pyruvate-to-lactate (kPL) via cytosolic lactate dehydrogenase and pyruvate-to-bicarbonate (kPB) via mitochondrial pyruvate dehydrogenase and carbonic anhydrase. Regions of interest included normal-appearing white matter (NAWM) and T2-hyperintense lesions (T2L), which were segmented from H-1 MR images and then aligned to the HP data. Carbon voxels containing >30% of NAWM or T2L were included in the analysis. Healthy controls demonstrated consistent kPL and kPB values over 4 scans in NAWM with SD/Mean of 5% and 12%, respectively. Compared to the median kPL-NAWM of 0.022s-1 in controls, the 5 patients had median serial kPL-NAWM values of 0.023, 0.023, 0.023, 0.029, and 0.015s-1, and mean serial ratios of kPL between T2L and NAWM (kPL-T2L/kPL-NAWM) of 1.22, 1.27, 1.05, 1.32, and 1.37s-1, indicating higher values in putative tumor. Median kPB-NAWM in controls was 0.004s-1 and ranged in patients 0.003-0.006s-1. Two patients with >4 serial scans, showed consistent kPL-NAWM over standard-of-care treatment and elevated kPL-T2L within new lesions, but up to 85% increase in kPL-NAWM with bevacizumab, which may be attributed to reduced BBB permeability. Stable patients generally demonstrated consistent kPL-T2L values that were lower compared to progressive patients. Future studies will include multi-parametric 1H imaging analysis in a larger patient population.

scholarly journals Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 687-698 ◽  
Author(s):  
Piotr Sowa ◽  
Hanne F Harbo ◽  
Nathan S White ◽  
Elisabeth G Celius ◽  
Hauke Bartsch ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Free Water ◽  
White Matter Lesions ◽  
Neurological Disability ◽  
Water Fraction ◽  
Neurite Density ◽  
Normal Appearing White Matter ◽  
Spectrum Imaging

Background: Restriction spectrum imaging (RSI) is a recently introduced magnetic resonance imaging diffusion technique. The utility of RSI in multiple sclerosis (MS) is unknown. Objective: To investigate the association between RSI-derived parameters and neurological disability in MS. Methods: Seventy-seven relapsing–remitting MS patients were scanned with RSI on a 3-T scanner. RSI-derived parameters: fast and slow apparent diffusion coefficient (sADC), fractional anisotropy, restricted fractional anisotropy, neurite density (ND), cellularity, extracellular water fraction, and free water fraction, were obtained in white matter lesions (WML) and normal appearing white matter (NAWM). Patients were divided into three groups according to their expanded disability status scale (EDSS): with minimal, low, and substantial disability (<2.5, 2.5–3, and >3, respectively). Group comparisons and correlation analyses were performed. Results: All tested RSI-derived parameters differed between WML and NAWM ( p < 0.001 for all pairwise comparisons). The sADC in WML showed largest difference across disability subgroups (analysis of variance (ANOVA): F = 5.1, η2 = 0.12, p = 0.008). ND in NAWM showed strongest correlation with disability (ϱ = –0.39, p < 0.001). Conclusion: The strongest correlation with EDSS of ND obtained in NAWM indicates that processes outside lesions are important for disability in MS. Our study suggests that RSI-derived parameters may help understand the “clinico-radiological paradox” and improve disease monitoring in MS.

Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012869
Author(s):  
Raffaello Bonacchi ◽  
Alessandro Meani ◽  
Elisabetta Pagani ◽  
Olga Marchesi ◽  
Andrea Falini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Linear Models ◽  
Gray Matter Volume ◽  
Age At Onset ◽  
Healthy Controls ◽  
Compensatory Mechanisms ◽  
Cross Sectional ◽  
Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

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