The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

Abstract

ObjectiveQuantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients.MethodsThirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue.ResultsIn patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e−16) and a significant increase in MTR (p-value < 1e−6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics—and not changes in lesions or brain volume—were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

Quantitative brain relaxation atlases for personalized detection and characterization of brain pathology

“…In consequence, this would prolong the scan time far beyond what is clinically acceptable, compromising the applicability of our approach. In addition, the proposed T 2 mapping strategy has been proved to deliver maps in agreement with conventional techniques and with excellent reproducibility, as well as good sensitivity toward T 2 alterations caused by pathologies . Lastly, it should be noted that fitting errors leading to an inaccurate estimation of T 1 and T 2 values were not discussed here, because these can be found in the original publications …”

“…In addition, the proposed T 2 mapping strategy has been proved to deliver maps in agreement with conventional techniques and with excellent reproducibility, 16 as well as good sensitivity toward T 2 alterations caused by pathologies. 4,6,46,47 Lastly, it should be noted that fitting errors leading to an inaccurate estimation of T 1 and T 2 values were not discussed here, because these can be found in the original publications. 14,16 The main limitation of our current HC is the narrow age range of healthy subjects included in the study and restricts the use of the method to patients whose ages fall into this very range.…”

“…Conversely, quantitative MRI (qMRI) techniques allow moving from such relative contrast information to a single, absolute measure of one or more separate tissue properties, hence providing the means for tissue characterization and the potential to gain further insight into microstructural changes caused by diseases . Moreover, the quantitative nature of the images may potentially overcome problems related to image reproducibility and interpretation, facilitating comparison in longitudinal and multi‐centric studies …”

“…3 Moreover, the quantitative nature of the images may potentially overcome problems related to image reproducibility and interpretation, facilitating comparison in longitudinal and multi-centric studies. 4,5 Brain relaxometry measures proved to be of value in several neurological diseases because alterations of T 1 and T 2 were related to neuronal cell death, axonal loss, and demyelination processes. [6][7][8] One target pathology for these techniques is multiple sclerosis (MS), a neurodegenerative and inflammatory disease of the central nervous system characterized by white matter (WM) and gray matter (GM) lesions, as well as inflammation of normal-appearing white matter (NAWM).…”

Clinical Applications of Synthetic MRI of the Brain

“…One possible explanation for non-enhancing MS lesions having relaxation and PD values that overlap with enhancing lesions is remyelination, which occurs in some lesions. [97][98][99] The number of enhancing MS lesions was rather small in this study, which is a limitation. Even though care was taken during manual ROI delineation of lesions not to include other structures to avoid partial volume, images were only available in the axial plane.…”