Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

Tardif, Christine; Bedell, Barry J.; Eskildsen, Simon Fristed; Collins, D. Louis; Pike, G. Bruce

doi:10.1155/2012/742018

Cited by 41 publications

(41 citation statements)

References 56 publications

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“…Besides demyelination, T 2 prolongation in MS can also be caused by edema and neuronal loss on a microstructural level (23,24). Histopathological studies have shown T 2 relaxation time to be associated with GM myelin content (32,33) and axonal density (33). In conclusion, T 2 relaxometry is an attractive imaging surrogate for measuring demyelination and loss of neural tissue in the living brain.…”

Section: Discussionmentioning

confidence: 92%

Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

et al. 2016

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T2 relaxation time is a quantitative MRI in vivo surrogate of cerebral tissue damage in multiple sclerosis (MS) patients. Cortical T2 prolongation is a known feature in later disease stages, but has not been demonstrated in the cortical normal appearing gray matter (NAGM) in early MS. This study centers on the quantitative evaluation of the tissue parameter T2 in cortical NAGM in a collective of early MS and clinically isolated syndrome (CIS) patients, hypothesizing that T2 prolongation is already present at early disease stages and variable over space, in line with global and focal inflammatory processes in MS. Additionally, magnetization transfer ratio (MTR) mapping was performed for further characterization of the expected cortical T2 alteration. Quantitative T2 and MTR maps were acquired from 12 patients with CIS and early MS, and 12 matched healthy controls. The lesion-free part of the cortical volume was identified, and the mean T2 and MTR values and their standard deviations within the cortical volume were determined. For evaluation of spatial specificity, cortical lobar subregions were tested separately for differences of mean T2 and T2 standard deviation. We detected significantly prolonged T2 in cortical NAGM in patients. T2 prolongation was found across the whole cerebral cortex and in all individual lobar subregions. Significantly higher standard deviations across the respective region of interest were found for the whole cerebral cortex and all subregions, suggesting the occurrence of spatially inhomogeneous cortical damage in all regions studied. A trend was observed for MTR reduction and increased MTR variability across the whole cortex in the MS group, suggesting demyelination. In conclusion, our results suggest that cortical damage in early MS is evidenced by spatially inhomogeneous T2 prolongation which goes beyond demyelination. Iron deposition, which is known to decrease T2, seems less prominent.

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Section: Discussionmentioning

confidence: 92%

Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

et al. 2016

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“…To this end, pathological processes such as demyelination, edema formation, tissue loss, and iron accumulation lead to variable changes in quantitative measures of proton relaxation times (T1, T2, and T2*) as well as in semiquantitative parameters such as the magnetization transfer ratio (MTR). 6 – 10 Thanks to recent MRI developments, 11 , 12 it is now possible to combine multiple q/sq MRI sequences in a clinically applicable protocol and gather more specific information about the nature of tissue pathology in MS.…”

Section: Introductionmentioning

confidence: 99%

Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis

Bonnier

Roche

Romascano

et al. 2014

Ann Clin Transl Neurol

124

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IntroductionIn patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients.MethodsBrain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates.ResultsQuantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: −4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R2 = 0.4), attention (P = 0.0005, Adj-R2 = 0.6), and disability (P = 0.03, Adj-R2 = 0.4).ConclusionAdvanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical–radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

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“…Despite its sensitivity to myeloarchitecture, T 2 * it is influenced by several confounds, such as the tissues iron level (Fukunaga et al, 2010), B0 field inhomogeneities (Hernando et al, 2012) and fibers orientation with respect to B0 (Cohen-Adad et al, 2012). Hence, combining T 2 * with another measure sensitive to myelin would increase the confidence in assessing the degree of myelination, as has been shown ex vivo (Tardif et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Multivariate combination of magnetization transfer, T 2 * and B0 orientation to study the myelo-architecture of the in vivo human cortex

et al. 2015

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Recently, T2* imaging at 7 tesla (T) MRI was shown to reveal microstructural features of the cortical myeloarchitecture thanks to an increase in contrast-to-noise ratio. However, several confounds hamper the specificity of T2* measures (iron content, blood vessels, tissues orientation). Another metric, magnetization transfer ratio (MTR), is known to also be sensitive to myelin content and thus would be an excellent complementary measure because its underlying contrast mechanisms are different than that from T2*. The goal of this study was thus to combine MTR and T2* using multivariate statistics in order to gain insights into cortical myelin content. Seven healthy subjects were scanned at 7T and 3T to obtain T2* and MTR data, respectively. A multivariate myelin estimation model (MMEM) was developed, and consists in (i) normalizing T2* and MTR values and (ii) extracting their shared information using independent component analysis (ICA). B0 orientation dependence and cortical thickness were also computed and included in the model. Results showed high correlation between MTR and T2* in the whole cortex (r=0.76, p<10−16), suggesting that both metrics are partly driven by a common source of contrast, here assumed to be the myelin. Average MTR and T2* were respectively 31.0 +/− 0.3% and 32.1 +/− 1.4 ms. Results of the MMEM spatial distribution showed similar trends to that from histological work stained for myelin (r=0.77, p<0.01). Significant right-left differences were detected in the primary motor cortex (p<0.05), the posterior cingulate cortex (p<0.05) and the visual cortex (p<0.05). This study demonstrates that MTR and T2* are highly correlated in the cortex. The combination of MTR, T2*, CT and B0 orientation may be a useful means to study cortical myeloarchitecture with more specificity than using any of the individual methods. The MMEM framework is extendable to other contrasts such as T1 and diffusion MRI.

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Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

Cited by 41 publications

References 56 publications

Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis

Multivariate combination of magnetization transfer, T 2 * and B0 orientation to study the myelo-architecture of the in vivo human cortex

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Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

Cited by 41 publications

References 56 publications

Assessment of cortical damage in early multiple sclerosis with quantitative T2 relaxometry

Assessment of cortical damage in early multiple sclerosis with quantitative T2 relaxometry

Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis

Multivariate combination of magnetization transfer, T 2 * and B0 orientation to study the myelo-architecture of the in vivo human cortex

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Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry