Diffusely Abnormal White Matter in Progressive Multiple Sclerosis: In Vivo Quantitative MR Imaging Characterization and Comparison between Disease Types

Vrenken, Hugo; Seewann, Alexandra; Knol, Dirk L.; Polman, Chris H.; Barkhof, Frederik; Geurts, Jeroen J. G.

doi:10.3174/ajnr.a1839

Cited by 49 publications

(59 citation statements)

References 27 publications

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“…This is consistent with previous findings where Vrenken et al (158) showed that DAWM was an intermediary in T1 . This may reflect the relative increase of the extracellular water of the tissues, where focal lesions have the highest increase, DAWM has a less pronounced increase, and NAWM only has a slight increase.…”

Section: Diffusely Abnormal White Mattersupporting

confidence: 83%

“…Recent studies, however, suggest that these changes may be important markers of disease progression (157,158). Technological developments have therefore been suggested to characterise and quantify DAWM, as well as to detect changes in NAWM.…”

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

“…These regions, which have fuzzy borders and a signal intensity that is intermediate between NAWM and focal MW lesions, are referred to as diffusely abnormal white matter, or dirty-appearing white matter (DAWM) (154)(155)(156)(157)(158). DAWM is believed to be either a separate pathological entity (155,157,158) or caused by Wallerian degeneration (156). Histopathological examinations have shown that DAWM has reduced axonal density as well as reduced myelin, but to a lesser extent than focal lesions (149,156,157,159).…”

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

“…Technological developments have therefore been suggested to characterise and quantify DAWM, as well as to detect changes in NAWM. These techniques include diffusion tensor imaging (DTI) (157,158,160), quantitative magnetisation transfer imaging (qMTI) (84,155,158), quantitative MR spectroscopy (qMRS) (161,162), and qMRI (84, 157, 158).…”

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

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Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis

West¹

2014

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Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear. In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation. The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions. One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration. This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem. This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.Bildtagning med magnetresonanstomografi (MRT) är en teknik som kan användas för att upptäcka lesioner i vit substans hos patienter med multipel skleros (MS), men sambandet mellan lesioner och klinisk funktionsnedsättning är svagt. På grund av detta har intresset för andra patologiska processer i hjärnan ökat. Exempel är förändringar i vit substans som ser normal ut vid MRT (NAWM) och även så kallad diffus vit vävnad (DAWM). Det är emellertid fortfarande oklart vilka mekanismer i MS som leder till klinisk funktionsnedsättning. Med kvantitativ MRT (qMRT) kan fysiologiska egenskaper i vävnaden, som till exempel relaxationstiderna (T1 och T2) samt protontäthet (PD), mätas. QMRT kan användas för att mäta förändringar i hjärnan hos MS patienter och des...

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Section: Diffusely Abnormal White Mattersupporting

confidence: 83%

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

See 2 more Smart Citations

Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis

West¹

2014

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“…24 Our findings that children with acute demyelinating syndromes consistent with either monofocal CIS, polyfocal CIS with encephalopathy, or polyfocal CIS without encephalopathy did not demonstrate significant anisotropic abnormalities in the NAWM suggest that these diffuse pathologic processes are not present acutely at the time of clinical disease onset. Our definition of NAWM excluded overt focal lesions but included dirty-appearing white matter, 25 and further studies are required to dissociate these entities in pediatric MS. Similar to our work, a recent study found significantly decreased mean FA in the NAWM callosal fibers and NAWM corticospinal tracts and significantly increased MD in the NAWM corticospinal tracts in adult MS compared with the pediatric MS/CIS and adult CIS groups.…”

Section: Discussionmentioning

confidence: 99%

Diffusion Tensor Analysis of Pediatric Multiple Sclerosis and Clinically Isolated Syndromes

Vishwas

Healy

Pienaar

et al. 2012

AJNR Am J Neuroradiol

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Tissue remodeling in periplaque regions of multiple sclerosis spinal cord lesions

Lieury

Chanal

Androdias

et al. 2014

Glia

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Our knowledge of multiple sclerosis (MS) neuropathology has benefited from a number of studies that provided an in-depth description of plaques and, more recently, diffuse alterations of the normal-appearing white or grey matter. However, there have been few studies focusing on the periplaque regions surrounding demyelinated plaques, notably in MS spinal cords. In this context, the present study aimed to analyze the molecular immunopathology of periplaque demyelinated lesions (PDLs) in the spinal cord of patients with a progressive form of MS. To achieve this goal, the neuropathological features of PDLs were analyzed in postmortem tissues derived from the cervical spinal cord of 21 patients with primary or secondary progressive MS. We found that PDLs covered unexpectedly large areas of incomplete demyelination and were characterized by the superimposition of pro- and anti-inflammatory molecular signatures. Accordingly, macrophages/microglia accumulated in PDLs but exhibited a poor phagocytic activity toward myelin debris. Interestingly, while genes of the oligodendrocyte lineage were consistently down-regulated in PDLs, astrocyte-related molecules such as aquaporin 4, connexin 43 and the glutamate transporter EAAT1, were significantly upregulated in PDLs at the mRNA and protein levels. Overall, our work indicates that in the spinal cord of patients with a progressive form of MS, a tissue remodeling process that is temporally remote from plaque development takes place in PDLs. We propose that in spinal cord PDLs, this process is supported by subtle alterations of astrocyte functions and by low-grade inflammatory events that drive a slowly progressive loss of myelin and a failure of remyelination.

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Diffusely Abnormal White Matter in Progressive Multiple Sclerosis: In Vivo Quantitative MR Imaging Characterization and Comparison between Disease Types

Cited by 49 publications

References 27 publications

Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis

Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis

Diffusion Tensor Analysis of Pediatric Multiple Sclerosis and Clinically Isolated Syndromes

Tissue remodeling in periplaque regions of multiple sclerosis spinal cord lesions

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