Author Of 3 Presentations
P0564 - Depth-dependent cortical distributions of quantitative 7 T MRI parameters are associated with disability in MS (ID 1842)
Abstract
Background
Alterations in the myelination and iron distribution of the cerebral cortex underlie abnormal cortical function in multiple sclerosis (MS). Due to the pathology, the transition from the inner layers to the outer layers (from white matter to the pial surface) of the cortex reflects changes in the cyto- and myeloarchitecture of the cortex. Cortical demyelination and iron deposition are relevant aspects of tissue damage and microstructural changes may affect each layer in the cortex differently.
Objectives
The purpose of this study was to assess the distribution of quantitative MRI (qMRI) measurements on the whole cortex and its sensitivity as clinically accessible biomarkers of grey matter (GM) pathology in MS.
Methods
45 participants with MS underwent 7T MRI of the brain. Magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) was processed for T1-weighted (T1w) images and a T1-map. Multi-echo gradient echo images were processed for quantitative susceptibility (χ) and R2* mapping. Cortical GM volumes were segmented into nine cortical layers and relaxometry metrics were calculated within layers. The layers were grouped in three regions, inner (0-30%), middle (31-70%) and outer region (71-100%), and the distributions of these relaxometry metrics throughout the cortical thickness were compared to collect disability scales.
Results
Significant Spearman correlations were found with Expanded Disability Status Scale (EDSS) for the slope of the linear regression of the median values in the inner region (T1: r = -0.587, p < 0.001; R2*: r = 0.610, p < 0.001; χ: r = 0.416, p < 0.010). With timed 25-foot walk (T25FW) (T1: r = -0.429, p < 0.010; R2*: r = 0.558, p < 0.001). With symbol digit modalities test (SDMT), middle region (T1: r = -0.389, p < 0.010; R2*: r = -0.328, p < 0.050; χ: r = -0.301, p < 0.050). With EDSS, outer region (R2*: r = -0.312, p < 0.050).
Conclusions
Cortical layer 7T qMRI analyses revealed pattern-specific distributions and regional relationships with disability in MS. These associations might show the increase in homogeneous myelin distribution and heterogeneous iron distribution locally throughout the cortical thickness. The strong relationships found between disability scales warrant further exploration as a novel outcome measure.
P0569 - Distribution profile of T1 relaxation time in white matter lesions on 7-Tesla MRI in multiple sclerosis reflects disease severity and phenotype (ID 1208)
Abstract
Background
Recent advancements in quantitative neuroimaging have revealed signal heterogeneity in multiple sclerosis (MS) brains. Although most work focuses on central tendency measures (i.e., mean or median), distribution features (i.e., density profile, skewness, kurtosis) of quantitative metrics from magnetic resonance image (MRI) may also provide insightful information about disease severity and progression.
Objectives
We aimed to characterize white matter lesion (WML), normal-appearing white matter (NAWM), and cortical gray matter (GM) in MS brains utilizing distribution features of T1 values from 7-Tesla (7T) MRI to demonstrate their potential as biomarkers of MS disease phenotype and disability.
Methods
Forty-eight participants with MS underwent brain MRI on a 7T scanner. Magnetization prepared 2 rapid gradient echo (MP2RAGE) image was acquired, and quantitative T1 relaxation times were calculated from two inversion images from the acquisition. T1-weighted image reconstructed from MP2RAGE was used for the segmentation of the brain into WML, NAWM, and GM tissue types. T1 values of all participants were concatenated and subgrouped by either disability or disease subtype. T1 distributions in three tissue segments were compared using cumulative distribution function and Two-sample Kolmogorov-Smirnov test (D-statistic). Associations of various T1 features with clinical measures were assessed by Spearman or Pearson methods with controlling for age, as appropriate.
Results
Concatenated T1 distribution of participants’ WML in groups with a higher disability or more progressive MS phenotype appeared wider and shifted toward a higher T1 value. For example, the higher disability group had a higher IQR of T1 (p = 0.040) and a higher median T1 (p = 0.018). The distribution profile of WML was distinctively different between low and high EDSS groups and relapsing versus progressive MS (D = 0.323, p = < 0.001; D = 0.314, p = < 0.001 respectively). Distribution profiles of NAWM and GM were also significantly different between groups, but the magnitude of the difference was smaller (D = 0.058 and D = 0.024, respectively). Despite the difference in the appearance of distribution profiles in WML between groups, skewness and kurtosis were not significantly different. Disability (measured as Expanded Disability Status Scale: EDSS) was significantly correlated with median T1 (rho = 0.405, p = 0.005) and skewness of T1 (rho = -0.301, p = 0.040) in WML, and median T1 (rho = 0.435, p = 0.002) and IQR of T1 (rho = 0.452, p = 0.001) in NAWM. Neither central tendency nor distribution measures in GM significantly correlated with EDSS.
Conclusions
Our study suggests that differences in T1 distribution between groups reflect increasing T1 values of WML as disease advances toward more severe status (i.e., higher disability or progressive MS). This finding supports T1 measures as a potential in vivo biomarker in the diagnosis and prognosis of MS brains.
P0655 - Tissue destruction and blood-brain barrier breakdown in chronic-active vs. inactive MS lesions by 7T MP2RAGE and susceptibility MRI (ID 996)
Abstract
Background
Recent imaging data in multiple sclerosis (MS) suggests that chronic-active lesions and inactive lesions can be differentiated based on the presence of paramagnetic rims on gradient-echo (GRE). At autopsy, chronic-active lesions show significant demyelination, oligodendrocyte loss, and outer rims of iron laden macrophages and activated microglia. Confirmation of the destructive nature of these lesions on MRI would provide in vivo evidence of their consequences. Further, evidence of local blood-brain barrier (BBB) breakdown in these lesions would provide further validation of their chronic-active state, along with suggesting a possible opportunity for therapeutic intervention.
Objectives
We aimed to determine if white matter lesions (WMLs) with paramagnetic rims show greater alterations in multiple signal characteristics, including our novel metric for BBB breakdown, Magnetization prepared 2 rapid gradient echo (MP2RAGE) ΔT1 mapping.
Methods
MP2RAGE and GRE images of the brain were acquired on 36 participants with MS on a 7T MRI before and after contrast. GRE images were processed for R2* and quantitative susceptibility maps (QSM). MP2RAGE was processed for T1 mapping and all images were registered to the pre-contrast T1-weighted (T1-w) image. ΔT1 maps were created by subtracting pre and post-contrast T1 maps. All WMLs were masked on T1-w and masks were separately created for lesions with visible paramagnetic rims on QSM. T1, ΔT1, χ (from QSM), and R2* values were compared across lesion types using a linear mixed effects model and Wilcoxon rank sum testing.
Results
Mean pre-contrast T1 was significantly higher in rimmed lesions (2.323, SE = 0.03964) compared to non-rimmed lesions (2.113, SE = 0.05791; p<0.001). Mean and median ΔT1 values were not significantly different in non-rimmed lesions versus rimmed lesions. Median pre-contrast χ values were significantly smaller in rimmed lesions (-0.00581, SE = 0.00277) versus non-rimmed lesions (-0.01298, SE = 0.003332; p = 0.011). Pre-contrast median R2* was significantly lower in rimmed lesions (24.55, SE = 0.8378) versus non-rimmed lesions (28.04, SE = 0.8919; p<0.001).
Conclusions
Elevated T1 and reduced χ and R2* in rimmed lesions in this study are confirmatory of greater demyelination and tissue destruction in this lesion subtype. The lack of significant difference in ΔT1 values suggests that there is no evidence of additional BBB breakdown in chronic-active lesions as measured on MRI.
Presenter Of 1 Presentation
P0569 - Distribution profile of T1 relaxation time in white matter lesions on 7-Tesla MRI in multiple sclerosis reflects disease severity and phenotype (ID 1208)
Abstract
Background
Recent advancements in quantitative neuroimaging have revealed signal heterogeneity in multiple sclerosis (MS) brains. Although most work focuses on central tendency measures (i.e., mean or median), distribution features (i.e., density profile, skewness, kurtosis) of quantitative metrics from magnetic resonance image (MRI) may also provide insightful information about disease severity and progression.
Objectives
We aimed to characterize white matter lesion (WML), normal-appearing white matter (NAWM), and cortical gray matter (GM) in MS brains utilizing distribution features of T1 values from 7-Tesla (7T) MRI to demonstrate their potential as biomarkers of MS disease phenotype and disability.
Methods
Forty-eight participants with MS underwent brain MRI on a 7T scanner. Magnetization prepared 2 rapid gradient echo (MP2RAGE) image was acquired, and quantitative T1 relaxation times were calculated from two inversion images from the acquisition. T1-weighted image reconstructed from MP2RAGE was used for the segmentation of the brain into WML, NAWM, and GM tissue types. T1 values of all participants were concatenated and subgrouped by either disability or disease subtype. T1 distributions in three tissue segments were compared using cumulative distribution function and Two-sample Kolmogorov-Smirnov test (D-statistic). Associations of various T1 features with clinical measures were assessed by Spearman or Pearson methods with controlling for age, as appropriate.
Results
Concatenated T1 distribution of participants’ WML in groups with a higher disability or more progressive MS phenotype appeared wider and shifted toward a higher T1 value. For example, the higher disability group had a higher IQR of T1 (p = 0.040) and a higher median T1 (p = 0.018). The distribution profile of WML was distinctively different between low and high EDSS groups and relapsing versus progressive MS (D = 0.323, p = < 0.001; D = 0.314, p = < 0.001 respectively). Distribution profiles of NAWM and GM were also significantly different between groups, but the magnitude of the difference was smaller (D = 0.058 and D = 0.024, respectively). Despite the difference in the appearance of distribution profiles in WML between groups, skewness and kurtosis were not significantly different. Disability (measured as Expanded Disability Status Scale: EDSS) was significantly correlated with median T1 (rho = 0.405, p = 0.005) and skewness of T1 (rho = -0.301, p = 0.040) in WML, and median T1 (rho = 0.435, p = 0.002) and IQR of T1 (rho = 0.452, p = 0.001) in NAWM. Neither central tendency nor distribution measures in GM significantly correlated with EDSS.
Conclusions
Our study suggests that differences in T1 distribution between groups reflect increasing T1 values of WML as disease advances toward more severe status (i.e., higher disability or progressive MS). This finding supports T1 measures as a potential in vivo biomarker in the diagnosis and prognosis of MS brains.