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Barbara Bellenberg

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YNICL Journal 2022 Journal Article

Relaxometry and brain myelin quantification with synthetic MRI in MS subtypes and their associations with spinal cord atrophy

  • Theodoros Ladopoulos
  • Britta Matusche
  • Barbara Bellenberg
  • Florian Heuser
  • Ralf Gold
  • Carsten Lukas
  • Ruth Schneider

Immune-mediated demyelination and neurodegeneration are pathophysiological hallmarks of Multiple Sclerosis (MS) and main drivers of disease related disability. The principal method for evaluating qualitatively demyelinating events in the clinical context is contrast-weighted magnetic resonance imaging (MRI). Moreover, advanced MRI sequences provide reliable quantification of brain myelin offering new opportunities to study tissue pathology in vivo. Towards neurodegenerative aspects of the disease, spinal cord atrophy - besides brain atrophy - is a powerful and validated predictor of disease progression. The etiology of spinal cord volume loss is still a matter of research, as it remains unclear whether the impact of local lesion pathology or the interaction with supra- and infratentorial axonal degeneration and demyelination of the long descending and ascending fiber tracts are the determining factors. Quantitative synthetic MR using a multiecho acquisition of saturation recovery pulse sequence provides fast automatic brain tissue and myelin volumetry based on R1 and R2 relaxation rates and proton density quantification, making it a promising modality for application in the clinical routine. In this cross sectional study a total of 91 MS patients and 31 control subjects were included to investigate group differences of global and regional measures of brain myelin and relaxation rates, in different MS subtypes, using QRAPMASTER sequence and SyMRI postprocessing software. Furthermore, we examined associations between these quantitative brain parameters and spinal cord atrophy to draw conclusions about possible pathophysiological relationships. Intracranial myelin volume fraction of the global brain exhibited statistically significant differences between control subjects (10.4%) and MS patients (RRMS 9.4%, PMS 8.1%). In a LASSO regression analysis with total brain lesion load, intracranial myelin volume fraction and brain parenchymal fraction, the intracranial myelin volume fraction was the variable with the highest impact on spinal cord atrophy (standardized coefficient 4.52). Regional supratentorial MRI metrics showed altered average myelin volume fraction, R1, R2 and proton density in MS patients compared to controls most pronounced in PMS. Interestingly, quantitative MRI parameters in supratentorial regions showed strong associations with upper cord atrophy, suggesting an important role of brain diffuse demyelination on spinal cord pathology possibly in the context of global disease activity. R1, R2 or proton density of the thalamus, cerebellum and brainstem correlated with upper cervical cord atrophy, probably reflecting the direct functional connection between these brain structures and the spinal cord as well as the effects of retrograde and anterograde axonal degeneration. By using Synthetic MR-derived myelin volume fraction, we were able to effectively detect significant differences of myelination in relapsing and progressive MS subtypes. Total intracranial brain myelin volume fraction seemed to predict spinal cord volume loss better than brain atrophy or total lesion load. Furthermore, demyelination in highly myelinated supratentorial regions, as an indicator of diffuse disease activity, as well as alterations of relaxation parameters in adjacent infratentorial and midbrain areas were strongly associated with upper cervical cord atrophy.

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YNICL Journal 2019 Journal Article

Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging

  • Paul Schmidt
  • Viola Pongratz
  • Pascal Küster
  • Dominik Meier
  • Jens Wuerfel
  • Carsten Lukas
  • Barbara Bellenberg
  • Frauke Zipp

Longitudinal analysis of white matter lesion changes on serial MRI has become an important parameter to study diseases with white-matter lesions. Here, we build on earlier work on cross-sectional lesion segmentation; we present a fully automatic pipeline for serial analysis of FLAIR-hyperintense white matter lesions. Our algorithm requires three-dimensional gradient echo T1- and FLAIR- weighted images at 3 Tesla as well as available cross-sectional lesion segmentations of both time points. Preprocessing steps include lesion filling and intrasubject registration. For segmentation of lesion changes, initial lesion maps of different time points are fused; herein changes in intensity are analyzed at the voxel level. Significance of lesion change is estimated by comparison with the difference distribution of FLAIR intensities within normal appearing white matter. The method is validated on MRI data of two time points from 40 subjects with multiple sclerosis derived from two different scanners (20 subjects per scanner). Manual segmentation of lesion increases served as gold standard. Across all lesion increases, voxel-wise Dice coefficient (0.7) as well as lesion-wise detection rate (0.8) and false-discovery rate (0.2) indicate good overall performance. Analysis of scans from a repositioning experiment in a single patient with multiple sclerosis did not yield a single false positive lesion. We also introduce the lesion change plot as a descriptive tool for the lesion change of individual patients with regard to both number and volume. An open source implementation of the algorithm is available at http://www.statistical-modeling.de/lst.html.

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