An Ultra-High Field Study of Cerebellar Pathology in Early Relapsing-Remitting Multiple Sclerosis Using MP2RAGE

Objectives: The aim of this study was to study focal cerebellar pathology in early stages of multiple sclerosis (MS) using ultra-high-field magnetization-prepared 2 inversion-contrast rapid gradient-echo (7T MP2RAGE). Materials and Methods: Twenty early-stage relapsing-remitting MS patients underwent an MP2RAGE acquisition at 7 T magnetic resonance imaging (MRI) (images acquired at 2 different resolutions: 0.58 x 0.58 x 0.58 mm(3), 7T_0.58, and 0.75 x 0.75 x 0.90 mm(3), 7T_0.75) and 3 T MRI (1.0 x 1.0 x 1.2 mm(3), 3T_1.0). Total cerebellar lesion load and volume andmean cerebellar lesion volume were compared across images using a Wilcoxon signed-rank test. Mean T1 relaxation times in lesions and normal-appearing tissue as well as contrast-to-noise ratio (CNR) measurements were also compared using a Wilcoxon signed-rank test. A multivariate analysis was applied to assess the contribution of MRI metrics to clinical performance in MS patients. Results: Both 7T_0.58 and 7T_0.75 MP2RAGE showed significantly higher lesion load compared with 3T_1.0 MP2RAGE (P < 0.001). Plaques that were judged as leukocortical in 7T_0.75 and 3T_1.0 MP2RAGEs were instead identified as WM lesions in 7T_0.58 MP2RAGE. Cortical lesion CNR was significantly higher in MP2RAGEs at 7 T than at 3 T. Total lesion load as well as total and mean lesion volume obtained at both 7 T and 3 T MP2RAGE significantly predicted attention (P < 0.05, adjusted R-2 = 0.5), verbal fluency (P < 0.01, adjusted R-2 = 0.6), and motor performance (P = 0.01, adjusted R-2 = 0.7). Conclusions: This study demonstrates the value of 7 T MP2RAGE to study the cerebellum in early MS patients. 7T_0.58 MP2RAGE provides a more accurate anatomical description of white and gray matter pathology compared with 7T_0.75 and 3T_1.0 MP2RAGE, likely due to the improved spatial resolution, lower partial volume effects, and higher CNR.

MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis

Fabio Amarù, Guillaume Bonnier, Cristina Granziera, Tobias Kober, Reto Meuli, Jean-Philippe Thiran

Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p < 0.01) than in the corresponding normal-appearing tissue in patients, indicating relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I (beta = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden.

Springer Heidelberg2014

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

Guillaume Bonnier, Cristina Granziera, Tom Hilbert, Tobias Kober, Reto Meuli, Gian Franco Piredda, Jean-Philippe Thiran

Purpose To exploit the improved comparability and hardware independency of quantitative MRI, databases of MR physical parameters in healthy tissue are required, to which tissue properties of patients can be compared. In this work, normative values for longitudinal and transverse relaxation times in the brain were established and tested in single-subject comparisons for detection of abnormal relaxation times. Methods Relaxometry maps of the brain were acquired from 52 healthy volunteers. After spatially normalizing the volumes into a common space, T-1 and T-2 inter-subject variability within the healthy cohort was modeled voxel-wise. A method for a single-subject comparison against the atlases was developed by computing z-scores with respect to the established healthy norms. The comparison was applied to two multiple sclerosis and one clinically isolated syndrome cases for a proof of concept. Results The established atlases exhibit a low variation in white matter structures (median RMSE of models equal to 32 ms for T-1 and 4 ms for T-2), indicating that relaxation times are in a narrow range for normal tissues. The proposed method for single-subject comparison detected relaxation time deviations from healthy norms in the example patient data sets. Relaxation times were found to be increased in brain lesions (mean z-scores >5). Moreover, subtle and confluent differences (z-scores similar to 2-4) were observed in clinically plausible regions (between lesions, corpus callosum). Conclusions Brain T-1 and T-2 quantitative norms were derived voxel-wise with low variability in healthy tissue. Example patient deviation maps demonstrated good sensitivity of the atlases for detecting relaxation time alterations.

WILEY2019

MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis

Fabio Amarù, Guillaume Bonnier, Cristina Granziera, Tobias Kober, Reto Meuli, Jean-Philippe Thiran

Springer Heidelberg2014