Scope of our MRI Research

MRI Outcomes for Autoimmune Neuroinflammatory Disorders

Magnetic Resonance Imaging (MRI) is one of the cornerstones in MS diagnosis. Number, localization and configuration of T2 hyperintense lesion and contrast enhancing lesions reflect disease burden and disease activity.  But clinical disability and lesion burden in MRI correlate only to a certain extent. This phenomenon is known as the "clinico-radiological paradox". Nonetheless lesion count and lesion volume are important secondary outcome measures in MS treatment trials and with the expertise of many years we perform lesion quantification in a standardized protocol.

In our research we focus on new MRI methods to improve MS lesion characterization (e.g. with susceptibility weighted imaging at 7 Tesla) or to evaluate normal appearing brain tissue with advanced neuroimaging techniques and analysis (e.g. brain atrophy assessment, diffusion tensor imaging, MR spectroscopy, resting state fMRI).

Examples from Recent Research Projects

Single-subject independent component analysis-based intensity normalization

Non-quantitative MRI is prone to intersubject intensity variation rendering signal intensity level based analyses limited. We developed a method that fuses non-quantitative routine T1-weighted (T1w), T2w, and T2w fluid-saturated inversion recovery sequences using independent component analysis and validate it on age and sex matched healthy controls.

The proposed method leads to consistent and independent components with a significantly reduced coefficient-of-variation across subjects, suggesting potential to serve as automatic intensity normalization and thus to enhance the power of intensity based statistical analyses. To exemplify this, we show that voxelwise statistical testing on single-subject independent components reveals in particular a widespread sex difference in white matter, which was previously shown using, for example, diffusion tensor imaging but unobservable in the native MRI contrasts.

In conclusion, our study shows that single-subject independent component analysis can be applied to routine sequences, thereby enhancing comparability in-between subjects. Unlike quantitative MRI, which requires specific sequences during acquisition, our method is applicable to existing MRI data.

Papazoglou et al. 2017, PMID: 28432780

Brain parenchymal damage in neuromyelitis optica spectrum disorder

Objective was to investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD.

We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different sta- tistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls.

DTI TBSS and DTI atlas-based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior tha- lamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences.

In conclusion, NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD.

Pache et al. 2016, PMID: 27012555

Lesion morphology in primary progressive and relapsing-remitting MS

Potential differences between primary progressive (PP) and relapsing-remitting (RR) multiple sclerosis (MS) have been controversially discussed. In this study, we compared lesion morphology and distribution in patients with PPMS and RRMS (nine in each group) using 7 T MRI. We found that gray and white matter lesions in PPMS and RRMS patients did not differ in their respective morphological characteristics (e.g., perivascular p = 0.863, hypointense rim p = 0.796, cortical lesion count p = 0.436). Although limited by a small sample size, our study results suggest that PPMS and RRMS, despite differences in disease course and clinical characteristics, exhibit identical lesion morphology under ultrahigh field MRI.

Kuchling et al. 2014, PMID: 24781284

Basal ganglia functional connectivity in multiple sclerosis patients with fatigue

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes.

We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density.

In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed.

In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex.

In conclusion, fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

Finke et al. 2015, PMID: 25392321

Selected Publications

Selected Publications

Papazoglou S, Würfel J, Paul F, Brandt AU, Scheel M. Single-subject independent component analysis-based intensity normalization in non-quantitative multi-modal structural MRI. Hum Brain Mapp. 2017 Apr 22. [Epub ahead of print] PMID: 28432780.

Schlemm L, Chien C, Bellmann-Strobl J, Dörr J, Wuerfel J, Brandt AU, Paul F, Scheel M. Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients. Mult Scler. 2016 Sep 1:1352458516670738. [Epub ahead of print] PMID: 27679460.

Finke C, Heine J, Pache F, Lacheta A, Borisow N, Kuchling J, Bellmann-Strobl J, Ruprecht K, Brandt AU, Paul F. Normal volumes and microstructural integrity of deep gray matter structures in AQP4+ NMOSD. Neurol Neuroimmunol Neuroinflamm. 2016 Apr 20;3(3):e229. PMID: 27144219.

Pache F, Zimmermann H, Finke C, Lacheta A, Papazoglou S, Kuchling J, Wuerfel J, Hamm B, Ruprecht K, Paul F, Brandt AU, Scheel M. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study. Eur Radiol. 2016 Mar 24. [Epub ahead of print] PMID: 27012555.

Doss S, Rinnenthal JL, Schmitz-Hübsch T, Brandt AU, Papazoglou S, Lux S, Maul S, Würfel J, Endres M, Klockgether T, Minnerop M, Paul F. Cerebellar
neurochemical alterations in spinocerebellar ataxia type 14 appear to include glutathione deficiency. J Neurol. 2015 Aug;262(8):1927-35. PMID: 26041613.

Finke C, Schlichting J, Papazoglou S, Scheel M, Freing A, Soemmer C, Pech LM, Pajkert A, Pfüller C, Wuerfel JT, Ploner CJ, Paul F, Brandt AU. Altered basal
ganglia functional connectivity in multiple sclerosis patients with fatigue. Mult Scler. 2015 Jun;21(7):925-34. PMID: 25392321.

Sinnecker T, Oberwahrenbrock T, Metz I, Zimmermann H, Pfueller CF, Harms L, Ruprecht K, Ramien C, Hahn K, Brück W, Niendorf T, Paul F, Brandt AU, Dörr J, Wuerfel J. Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning--an ultrahigh-field MR pilot study. Eur Radiol. 2015 Jan;25(1):122-31. PMID: 25129119.

Finke C, Kopp UA, Scheel M, Pech LM, Soemmer C, Schlichting J, Leypoldt F, Brandt AU, Wuerfel J, Probst C, Ploner CJ, Prüss H, Paul F. Functional and
structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2013 Aug;74(2):284-96. PMID: 23686722.

Young KL, Brandt AU, Petzold A, Reitz LY, Lintze F, Paul F, Martin R, Schippling S. Loss of retinal nerve fibre layer axons indicates white but not
grey matter damage in early multiple sclerosis. Eur J Neurol. 2013 May;20(5):803-11. PMID: 23369013.

Zimmermann H, Freing A, Kaufhold F, Gaede G, Bohn E, Bock M, Oberwahrenbrock T, Young KL, Dörr J, Wuerfel JT, Schippling S, Paul F, Brandt AU. Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations. Mult Scler. 2013 Apr;19(4):443-50. PMID: 22936335.

Sinnecker T, Bozin I, Dörr J, Pfueller CF, Harms L, Niendorf T, Brandt AU, Paul F, Wuerfel J. Periventricular venous density in multiple sclerosis is
inversely associated with T2 lesion count: a 7 Tesla MRI study. Mult Scler. 2013 Mar;19(3):316-25. PMID: 22736752.

Pfueller CF, Brandt AU, Schubert F, Bock M, Walaszek B, Waiczies H, Schwenteck T, Dörr J, Bellmann-Strobl J, Mohr C, Weinges-Evers N, Ittermann B,
Wuerfel JT, Paul F. Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis. PLoS One. 2011 Apr 6;6(4):e18019. PMID: 21494672.

Dörr J, Wernecke KD, Bock M, Gaede G, Wuerfel JT, Pfueller CF, Bellmann-Strobl J, Freing A, Brandt AU, Friedemann P. Association of retinal and
macular damage with brain atrophy in multiple sclerosis. PLoS One. 2011 Apr 8;6(4):e18132. PMID: 21494659.

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