Automated Detection and Segmentation of Multiple Sclerosis Lesions Using Ultra-High-Field MP2RAGE

Objectives The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI. Materials and Methods The proposed prototype (MSLAST [Multiple Sclerosis Lesion Analysis at Seven Tesla]) takes as input a single image contrast derived from the 7T MP2RAGE prototype sequence and is based on partial volume estimation and topological constraints. First, MSLAST performs a skull-strip of MP2RAGE images and computes tissue concentration maps for WM, gray matter (GM), and cerebrospinal fluid (CSF) using a partial volume model of tissues within each voxel. Second, MSLAST performs (1) connected-component analysis to GM and CSF concentration maps to classify small isolated components as MS lesions; (2) hole-filling in the WM concentration map to classify areas with low WM concentration surrounded by WM (ie, MS lesions); and (3) outlier rejection to the WM mask to improve the classification of small WM lesions. Third, MSLAST unifies the 3 maps obtained from 1, 2, and 3 processing steps to generate a global lesion mask. Results Quantitative and qualitative assessments were performed using MSLAST in 25 MS patients from 2 research centers. Overall, MSLAST detected a median of 71% of MS lesions, specifically 74% of WM and 58% of cortical lesions, when a minimum lesion size of 6 mu L was considered. The median false-positive rate was 40%. When a 15 mu L minimal lesions size was applied, which is the approximation of the minimal size recommended for 1.5/3 T images, the median detection rate was 80% for WM and 63% for cortical lesions, respectively, and the median false-positive rate was 33%. We observed high correlation between MSLAST and manual segmentations (Spearman rank correlation coefficient, rho = 0.91), although MSLAST underestimated the total lesion volume (average difference of 1.1 mL), especially in patients with high lesion loads. MSLAST also showed good scan-rescan repeatability within the same session with an average absolute volume difference and F1 score of 0.38 +/- 0.32 mL and 84%, respectively. Conclusions We propose a new methodology to facilitate the segmentation of WM and cortical MS lesions at 7 T MRI, our approach uses a single MP2RAGE scan and may be of special interest to clinicians and researchers.

Quantitative Susceptibility Mapping in the Human Brain

Diana Khabipova

Magnetic resonance imaging (MRI) offers a good tissue contrast and the ability to visualize many disease related morphologies. The work presented in this thesis investigates the study of underlying structure of the brain using quantitative methods with a special emphasis on quantitative susceptibility mapping (QSM). Magnetic susceptibility reflects the interaction of a material to the magnetic field and measures in biological tissues the magnetic susceptibility of inclusions. The reconstruction of QSM requires further processing steps as the magnetic field produced by the sources needs to be disentangled from the orders of magnitude bigger background field. The produced field also depends not only on the shape and the orientation, but also on the anisotropy of susceptibility and the microstructural compartmentalization of the biological source. For this reason, reconstruction methods need to be capable to calculate accurate values for different brain regions as well as applicable in the everyday clinical diagnosis. Within the framework of the thesis a data acquisition protocol based on a multiple-echo gradient echo sequence as well as a post-processing protocol was implemented. One of the processing steps, the background removal method, was applied to preserve the brain regions close to the cerebrospinal fluid (CSF). This method outperforms state of the art methods in this regions but is computationally intensive. Different brain regions were studied using quantitative methods with special emphasis on the QSM. A new method, modulated closed form solution, with extremely fast computational time is proposed. The comparison with other single orientation methods revealed similar results and the highest correlation to the state-of-the-art method (COSMOS) in the deep gray matter. The R2* maps calculated from the same dataset are also able to distinguish the deep gray matter structures with a similar quality. However, QSM shows a higher sensitivity in early stage multiple sclerosis lesions as well as white matter-gray matter structures. In the human cortex the obtained cortical maps show enhancement of primary sensory cortex, which is known to be highly myelinated, on three evaluated quantitative contrasts R1,R2* and susceptibility. The contrasts based on the relaxation rates, R1 and R2*, show a monotonically decrease from the white matter to the CSF imitating the decrease in iron and myelin. The susceptibility behaviour is more complex as iron and myelin content introduce an opposing sensitivity, allowing to study iron and myelin content when combining the three contrasts. The microstructural organization of white matter influences the R2*, R2 as well as field map from which QSM is calculated. This structure leads to an orientation dependence of the studied contrasts and for QSM the spherical assumption is not valid anymore. Therefore a new QSM method is introduced, which includes the Lorentzian correction in white matter. Main fibres such as forceps major and minor were analysed for the three different quantitative contrasts. The anisotropic component associated with susceptibility is similar for the relaxation rates whereas the isotropic component of R2* shows a higher variability. The resulting deep gray matter structure of the new QSM method remained similar to the state-of-the-art method when comparing the isotropic component but calculates physically meaningful susceptibility maps with improved contrast between known fibre bundles.

EPFL2016

MP2RAGE multiple sclerosis magnetic resonance imaging at 3 T

Cristina Granziera, Rolf Gruetter, Tobias Kober, Reto Meuli, Delphine Ribes Lemay

Objectives: Lesion detection and characterization in multiple sclerosis (MS) are an essential part of its clinical diagnosis and an important research field. In this pilot study, we applied the recently introduced two inversion-contrast magnetization-prepared rapid gradient echo sequence (MP2RAGE) to patients with early-stage MS. Materials and Methods: The MP2RAGE is a 3-dimensional (3D) magnetization-prepared rapid gradient echo derivative providing homogeneous T1 weighting and simultaneous T1 mapping. The MP2RAGE performance was compared with that of 2 clinical routine sequences (2D fluid-attenuated inversion recovery [FLAIR] and 3D magnetization-prepared rapid gradient echo [MP-RAGE]) and 2 state-of-the art clinical research sequences (the 3D FLAIR-SPACE [sampling perfection with application-optimized contrasts by using different flip-angle evolutions], a fluid-attenuated variable flip-angle fast spin echo technique, and the 3D double-inversion recovery SPACE). A cohort of 10 early-stage female MS patients (age, 31.6 ± 4.7 years; disease duration, 3.8 ± 1.9 years; median expanded disability status scale score, 1.75) and 10 age- and gender-matched controls were enrolled after approval of the local institutional review board was obtained. Multiple sclerosis lesions were identified and assigned to brain locations and tissue types by two experienced physicians in all 5 contrasts. Subsequently, lesions were manually delineated for comparison and statistical analysis of lesion count, volume and quantitative measures. Results and Conclusions: The results show that the 3D T1-weighted high-resolution MP2RAGE contrast provides a sensitive means for MS lesion assessment. The additional quantitative T1 relaxation time maps obtained with the MP2RAGE provide further potential diagnostic and prognostic information that could help (a) to better discriminate lesion subtypes and (b) to stage and predict the activity and the evolution of MS. Results also indicate that the T2-weighted double-inversion recovery and FLAIR-SPACE contrasts are attractive complements to the MP2RAGE for lesion detection. Copyright © 2012 by Lippincott Williams & Wilkins.

2012

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