<scp>T2</scp> Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing–Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance

Papadaki, Efrosini; Mastorodemos, Vasileios; Panou, Τheodora; Pouli, Styliani; Spyridaki, Eirini; Kavroulakis, Eleftherios; Kalaitzakis, Georgios; Maris, Thomas G.; Simos, Panagiotis G.

doi:10.1002/jmri.27661

Cited by 6 publications

(10 citation statements)

References 35 publications

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“… 37 Papadaki et al. found DAWM T 2 of intra/extracellular and myelin water predicted visuomotor coordination and manual dexterity in CIS, supporting the potential clinical significance of DAWM microstructural changes in CIS and MS disease manifestation 29 . Finally, Vrenken et al.…”

Section: Introductionmentioning

confidence: 89%

“…37 Papadaki et al found DAWM T 2 of intra/extracellular and myelin water predicted visuomotor coordination and manual dexterity in CIS, supporting the potential clinical significance of DAWM microstructural changes in CIS and MS disease manifestation. 29 Finally, Vrenken et al suggest that DAWM may differ between PPMS and SPMS, with SPMS DAWM exhibiting more severe T 1 and MTR abnormalities than PPMS (Figure 6). 48 It is important to keep in mind that many advanced imaging metrics are influenced by similar mechanisms and are, thus, at least partially related to each other.…”

Section: Identification Of Dawmmentioning

confidence: 97%

“…DAWM often covers white matter areas far larger than typical plaques, 26 is commonly found near the occipital horns of the lateral ventricles, and can be adjacent to focal plaques or not be associated with any visible lesions. 24,[26][27][28][29]…”

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

“…Inflammation and water-related metrics, including T 1 , T 1,free , T 1,rho , T 2,rho , T 2 , apparent diffusion coefficient, mean diffusivity, and water content, are all increased in DAWM relative to NAWM, suggesting extracellular expansion and increased water mobility. 28,29,32,33,38,[46][47][48][49] Magnetization transfer ratio (MTR), a nonspecific but very sensitive measure of tissue damage influenced by myelin, axons, and inflammation, is consistently reduced in DAWM relative to NAWM, in both region of interest and histogram-based analysis (Figure 4). 26,32,33,39,[47][48][49] Magnetization transfer rate (k for ) is also reduced in DAWM, which may reflect altered microstructural tissue dynamics.…”

Section: Identification Of Dawmmentioning

confidence: 99%

“… 21,24,25 DAWM has poorly defined boundaries and extends across at least two consecutive 3–5 mm thick MRI slices. DAWM often covers white matter areas far larger than typical plaques, 26 is commonly found near the occipital horns of the lateral ventricles, and can be adjacent to focal plaques or not be associated with any visible lesions 24,26–29 …”

Section: Introductionmentioning

confidence: 99%

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Diffusely abnormal white matter in multiple sclerosis

Cairns

Vavasour

Traboulsee

et al. 2021

Journal of Neuroimaging

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MRI enables detailed in vivo depiction of multiple sclerosis (MS) pathology. Localized areas of MS damage, commonly referred to as lesions, or plaques, have been a focus of clinical and research MRI studies for over four decades. A nonplaque MRI abnormality which is present in at least 25% of MS patients but has received far less attention is diffusely abnormal white matter (DAWM). DAWM has poorly defined boundaries and a signal intensity that is between normal-appearing white matter and classic lesions on proton density and T 2 -weighted images. All clinical phenotypes of MS demonstrate DAWM, including clinically isolated syndrome, where DAWM is associated with higher lesion volume, reduced brain volume, and earlier conversion to MS. Advanced MRI metric abnormalities in DAWM tend to be greater than those in NAWM, but not as severe as focal lesions, with myelin, axons, and water-related changes commonly reported. Histological studies demonstrate a primary lipid abnormality in DAWM, with some axonal damage and lesser involvement of myelin proteins. This review provides an overview of DAWM identification, summarizes in vivo and postmortem observations, and comments on potential pathophysiological mechanisms, which may underlie DAWM in MS. Given the prevalence and potential clinical impact of DAWM, the number of imaging studies focusing on DAWM is insufficient. Characterization of DAWM significance and microstructure would benefit from larger longitudinal and additional quantitative imaging efforts. Revisiting data from previous studies that included proton density and T 2 imaging would enable retrospective DAWM identification and analysis.

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Section: Introductionmentioning

confidence: 89%

Section: Identification Of Dawmmentioning

confidence: 97%

Section: Diffusely Abnormal White Mattermentioning

confidence: 99%

Section: Identification Of Dawmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diffusely abnormal white matter in multiple sclerosis

Cairns

Vavasour

Traboulsee

et al. 2021

Journal of Neuroimaging

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Non‐lesional white matter in relapsing–remitting multiple sclerosis assessed by multicomponent T2 relaxation

Bontempi,

Rozzanigo,

Marangoni

et al. 2023

Brain and Behavior

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IntroductionThe purpose of the study is to investigate, by T2 relaxation, non‐lesional white matter (WM) in relapsing–remitting (RR) multiple sclerosis (MS).MethodsTwenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid‐Attenuated Inversion‐Recovery (FLAIR), 3D‐T1‐weighted, and T2‐relaxation multi‐echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub‐volumes with T1 hypo‐intensity. Non‐lesional WM was obtained as the segmented WM, excluding FL volumes. The multi‐echo sequence allowed decomposition into myelin water, intra‐extracellular water, and free water (Fw), which were evaluated on the segmented non‐lesional WM. Correlation analysis was performed between the non‐lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo‐intense FL volumes.ResultsThe T1 hypo‐intense FL volumes correlated with EDSS. On the non‐lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo‐intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2‐relaxation parameters did not improve significance.ConclusionT2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS‐predictors independent from FL sub‐volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration.

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Distinct hemodynamic and functional connectivity features of fatigue in clinically isolated syndrome and multiple sclerosis: accounting for the confounding effect of concurrent depression symptoms

et al. 2023

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Purpose This study aims to identify common and distinct hemodynamic and functional connectivity (FC) features for self-rated fatigue and depression symptoms in patients with clinically isolated syndrome (CIS) and relapsing–remitting multiple sclerosis (RR-MS). Methods Twenty-four CIS, 29 RR-MS patients, and 39 healthy volunteers were examined using resting-state fMRI (rs-fMRI) to obtain whole-brain maps of (i) hemodynamic response patterns (through time shift analysis), (ii) FC (via intrinsic connectivity contrast maps), and (iii) coupling between hemodynamic response patterns and FC. Each regional map was correlated with fatigue scores, controlling for depression, and with depression scores, controlling for fatigue. Results In CIS patients, the severity of fatigue was associated with accelerated hemodynamic response in the insula, hyperconnectivity of the superior frontal gyrus, and evidence of reduced hemodynamics–FC coupling in the left amygdala. In contrast, depression severity was associated with accelerated hemodynamic response in the right limbic temporal pole, hypoconnectivity of the anterior cingulate gyrus, and increased hemodynamics–FC coupling in the left amygdala. In RR-MS patients, fatigue was associated with accelerated hemodynamic response in the insula and medial superior frontal cortex, increased functional role of the left amygdala, and hypoconnectivity of the dorsal orbitofrontal cortex, while depression symptom severity was linked to delayed hemodynamic response in the medial superior frontal gyrus; hypoconnectivity of the insula, ventromedial thalamus, dorsolateral prefrontal cortex, and posterior cingulate; and decreased hemodynamics–FC coupling of the medial orbitofrontal cortex. Conclusion There are distinct FC and hemodynamic responses, as well as different magnitude and topography of hemodynamic connectivity coupling, associated with fatigue and depression in early and later stages of MS.

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T2 Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing–Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance

Cited by 6 publications

References 35 publications

Diffusely abnormal white matter in multiple sclerosis

Diffusely abnormal white matter in multiple sclerosis

Non‐lesional white matter in relapsing–remitting multiple sclerosis assessed by multicomponent T2 relaxation

Distinct hemodynamic and functional connectivity features of fatigue in clinically isolated syndrome and multiple sclerosis: accounting for the confounding effect of concurrent depression symptoms

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