Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis

Background Although MRI measures of grey matter abnormality correlate with clinical disability in multiple sclerosis, it is uncertain whether grey matter abnormality measured on MRI is entirely due to a primary grey matter process or whether it is partly related to disease in the white matter. Methods To explore potential mechanisms of grey matter damage we assessed the relationship of white matter T2 lesion volume, T1 lesion volume, and mean lesion magnetisation transfer ratio (MTR), with MRI measures of tissue atrophy and MTR in the grey matter in 117 subjects with secondary progressive multiple sclerosis. Results Grey matter fraction and mean grey matter MTR were strongly associated with lesion volumes and lesion MTR mean ( r = ±0.63–0.72). In contrast, only weak to moderate correlations existed between white matter and lesion measures. In a stepwise regression model, T1 lesion volume was the only independent lesion correlate of grey matter fraction and accounted for 52% of the variance. Lesion MTR mean and T2 lesion volume were independent correlates of mean grey matter MTR, accounting for 57% of the variance. Conclusions Axonal transection within lesions with secondary degeneration into the grey matter may explain the relationship between T1 lesions and grey matter fraction. A parallel accumulation of demyelinating lesions in white and grey matter may contribute to the association of T2 lesion volume and lesion MTR with grey matter MTR.

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T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation

Multiple Sclerosis Journal ◽

10.1177/135245859800400502 ◽

1998 ◽

Vol 4 (5) ◽

pp. 408-412 ◽

Cited By ~ 18

Author(s):

J I O'Riordan ◽

M Gawne Cain ◽

A Coles ◽

L Wang ◽

D AS Compston ◽

...

Keyword(s):

Multiple Sclerosis ◽

Strong Correlation ◽

Measurement Techniques ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Lesion Volume ◽

Mri Findings ◽

Lesion Load ◽

Post Contrast ◽

Secondary Progressive

Magnetic resonance imaging (MRI) is increasingly being used as a monitoring tool for disease activity in therapeutic trials in multiple sclerosis. There is, however, only a limited relationship between MRI findings and clinical outcome measurements. It has been suggested that hypointense lesion load on T1 weighted imaging has a better correlation with disability than the more conventional T2 hyper intense lesion load. This study was undertaken to (i) evaluate different measurement techniques used to quantify T1 hypointense lesion load, and (ii) to compare lesion load as measured using different parameters and disability. Twenty-five patients with secondary progressive multiple sclerosis, mean age of 40 years (23-57), mean EDSS 5.7 (4-7) were analysed. T2 lesion load on FSE correlated well with both the hypointense lesion load on T1 pre-gadolinium (r=0.8, P50.0001) and T1 post-gadolinium (r=0.8, P50.0001) but less so with the enhancing lesion load (r=0.4, P50.05). There was a very strong correlation with T1 hypo-intense lesion volume pre and post gadolinium (r=0.96, P50.001). However, the EDSS was not correlated with the T2 lesion load (r=70.27, P=0.2), T1 pre-gadolinium load (r=70.3, P=0.1), T1 post gadolinium load (r=70.4, P=0.7) and enhancing lesion load (r=70.28, P=0.2), or with the degree of hypointensity of T1 weighted images determined using the threshold technique. There is a strong correlation between T1 hypointense lesion volume both pre and post gadolinium and also between T1 and T2 lesion volumes.

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Atrophied Brain T2 Lesion Volume at MRI Is Associated with Disability Progression and Conversion to Secondary Progressive Multiple Sclerosis

Radiology ◽

10.1148/radiol.2019190306 ◽

2019 ◽

Vol 293 (2) ◽

pp. 424-433 ◽

Cited By ~ 11

Author(s):

Antonia Valentina Genovese ◽

Jesper Hagemeier ◽

Niels Bergsland ◽

Dejan Jakimovski ◽

Michael G. Dwyer ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Lesion Volume ◽

Disability Progression ◽

Secondary Progressive

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Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis

Journal of Neurology ◽

10.1007/s00415-009-0110-4 ◽

2009 ◽

Vol 256 (3) ◽

pp. 427-435 ◽

Cited By ~ 21

Author(s):

T. Hayton ◽

J. Furby ◽

K. J. Smith ◽

D. R. Altmann ◽

R. Brenner ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neurological Deficit ◽

Grey Matter ◽

Magnetization Transfer ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Magnetization Transfer Ratio ◽

Transfer Ratio ◽

Secondary Progressive

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Adenosine A2A Receptors in Secondary Progressive Multiple Sclerosis: A [11C]TMSX Brain PET Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.85 ◽

2013 ◽

Vol 33 (9) ◽

pp. 1394-1401 ◽

Cited By ~ 50

Author(s):

Eero Rissanen ◽

Jere R Virta ◽

Teemu Paavilainen ◽

Jouni Tuisku ◽

Semi Helin ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Pet Imaging ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Adenosine A2a Receptors ◽

A2a Receptors ◽

Secondary Progressive ◽

Normal Appearing White Matter ◽

Adenosine A2a

In this study, positron emission tomography (PET) imaging with a radioligand to adenosine A2A receptors (A2AR)—a potent regulator of inflammation—was used to gain insight into the molecular alterations in normal-appearing white matter (NAWM) and gray matter (GM) in secondary progressive multiple sclerosis (SPMS). Normal-appearing white matter and GM, despite seeming normal in conventional mangnetic resonance imaging (MRI), are important loci of widespread inflammation, neuronal damage, and source of progressive disability in multiple sclerosis (MS). Dynamic PET imaging using A2AR-specific [ 11 C]TMSX and brain MRI with diffusion tensor imaging were performed to eight SPMS patients and seven healthy controls. Distribution volumes ( VT) of [ 11 C]TMSX were analyzed from 13 regions of interest using Logan plot with arterial plasma input. The SPMS patients had significantly increased [ 11 C]TMSX- VT in NAWM compared with controls (mean (s.d.): 0.55 (± 0.08) vs. 0.45 (± 0.05); P = 0.036). Both the increased VT and the decreased fractional anisotropy (FA) in NAWM were associated with higher expanded disability status scale (EDSS) scores ( P = 0.030 and P = 0.012, respectively), whereas the T2-lesion load of SPMS patients did not correlate with EDSS. This study shows, that A2ARs are increased in the brain of SPMS patients, and that [ 11 C]TMSX-PET provides a novel approach to learn about central nervous system pathology in SPMS in vivo.

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The relationship between white matter fiber damage and gray matter perfusion in large-scale functionally defined networks in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517691149 ◽

2017 ◽

Vol 23 (14) ◽

pp. 1884-1892 ◽

Cited By ~ 4

Author(s):

Ashley Y Ma ◽

Rita C Vitorino ◽

Seyed-Parsa Hojjat ◽

Alannah D Mulholland ◽

Liying Zhang ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Large Scale ◽

Progressive Multiple Sclerosis ◽

Functional Networks ◽

Lesion Volume ◽

Fiber Damage ◽

Damage Extent ◽

The Relationship

Background: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. Objective: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients. Methods: Magnetic resonance imaging (MRI) and neurocognitive testing were performed on 19 healthy controls (HC), 39 RRMS, and 45 SPMS patients. WM damage extent and severity were quantified with T2-hyper/T1-hypointense (T2h/T1h) lesion volume and degree of perfusion reduction in lesional and normal-appearing white matter (NAWM), respectively. A two-step linear regression corrected for confounders was employed. Results: Cognitive impairment was present in 20/39 (51%) RRMS and 25/45 (53%) SPMS patients. GM node perfusion was associated with WM fiber damage severity (WM hypoperfusion) within each network—including both NAWM ( R2 = 0.67–0.89, p < 0.0001) and T2h ( R2 = 0.39–0.62, p < 0.0001) WM regions—but was not significantly associated ( p > 0.01) with WM fiber damage extent (i.e. T2h/T1h lesion volumes). Conclusion: Overall, GM node perfusion was associated with severity rather than extent of WM network damage, supporting a primary etiology of GM hypoperfusion.

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7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis

Brain ◽

10.1093/brain/awaa249 ◽

2020 ◽

Vol 143 (10) ◽

pp. 2973-2987 ◽

Cited By ~ 1

Author(s):

Russell Ouellette ◽

Constantina A Treaba ◽

Tobias Granberg ◽

Elena Herranz ◽

Valeria Barletta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

White Matter ◽

Cervical Spinal Cord ◽

White Matter Lesions ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Spinal Cord Lesions ◽

Secondary Progressive ◽

Relapsing Remitting

Abstract We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein. Brain imaging at 7 T was used to segment cortical and white matter lesions and 3 T imaging for cortical thickness estimation. Cervical spinal cord lesions were mapped voxel-wise as a function of distance from the inner central canal CSF pool to the outer subpial surface. Similarly, brain white matter lesions were mapped voxel-wise as a function of distance from the ventricular system. Subjects with relapsing-remitting multiple sclerosis showed a greater predominance of spinal cord lesions nearer the outer subpial surface compared to secondary progressive cases. Inversely, secondary progressive participants presented with more centrally located lesions. Within the brain, there was a strong gradient of lesion formation nearest the ventricular system that was most evident in participants with secondary progressive multiple sclerosis. Lesion fractions within the spinal cord grey and white matter were related to the lesion fraction in cerebral white matter. Cortical thinning was the primary determinant of the Expanded Disability Status Scale, white matter lesion fractions in the spinal cord and brain of the 9-Hole Peg Test and cortical thickness and spinal cord grey matter cross-sectional area of the Timed 25-Foot Walk. Spinal cord lesions were localized nearest the subpial surfaces for those with relapsing-remitting and the central canal CSF surface in progressive disease, possibly implying CSF-mediated pathogenic mechanisms in lesion development that may differ between multiple sclerosis subtypes. These findings show that spinal cord lesions involve both grey and white matter from the early multiple sclerosis stages and occur mostly independent from brain pathology. Despite the prevalence of cervical spinal cord lesions and atrophy, brain pathology seems more strongly related to physical disability as measured by the Expanded Disability Status Scale.

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Cortical grey matter ratio differentiates relapsing remitting multiple sclerosis from secondary progressive multiple sclerosis

10.26226/morressier.59a96e1ed462b8028d895b01 ◽

2017 ◽

Author(s):

Jeroen Fleer

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Secondary Progressive ◽

Relapsing Remitting ◽

Cortical Grey Matter ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515622694 ◽

2016 ◽

Vol 22 (11) ◽

pp. 1429-1437 ◽

Cited By ~ 19

Author(s):

Kim A Meijer ◽

Nils Muhlert ◽

Mara Cercignani ◽

Varun Sethi ◽

Maria A Ron ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Cognitive Domains ◽

Secondary Progressive ◽

Relapsing Remitting ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis ◽

Tract Damage

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

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