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Uwe Klose

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YNICL Journal 2023 Journal Article

MR-spectroscopy in metachromatic leukodystrophy: A model free approach and clinical correlation

  • Joana Feldmann
  • Pascal Martin
  • Benjamin Bender
  • Lucia Laugwitz
  • Laimdota Zizmare
  • Christoph Trautwein
  • Ingeborg Krägeloh-Mann
  • Uwe Klose

BACKGROUND AND PURPOSE: Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to demyelination and subsequently to a progressive decline in cognitive and motor function. It affects mainly white matter where changes during the course of the disease can be visualized on T2-weighted MRI as hyperintense areas. Associated changes in brain metabolism can be quantified by MR spectroscopy (MRS) and may give complementary information as biomarkers for disease characterisation and progression. Our study aimed to further investigate the correlation of MRS with clinical parameters for motor and cognitive function by using a model free MRS analysis approach that would be precise and straightforward to implement. MATERIALS AND METHODS: H (proton) nuclear magnetic resonance (NMR) spectroscopy. The applied interval integration method was validated in the control cohort against the standard approach, using spectral profile templates of known metabolites (LCModel). Both methods showed good agreement, with coefficients of variance being slightly lower for our approach compared to the related LCModel results. Moreover, the new approach was able to extract information out of the frequency range around the main peaks of aspartate and glutamine where LCModel showed only few usable values for the respective metabolites. RESULTS: MLD spectra clearly differed from controls. The most pronounced differences were found in white matter (much less in grey matter), with larger values corresponding to main peaks of myo-inositol, choline and aspartate, and smaller values associated with NAA and glutamine. Late-infantile patients had more severe changes compared to later-onset patients, especially in intervals corresponding to NAA, aspartate, myo-inositol, choline and glutamine. There was a high correlation of several intervals in the corticospinal tract region with motor function (with the most relevant interval corresponding to NAA peak with a correlation coefficient of -0.75; p < 0.001), while cognitive function, by means of IQ, was found to be most correlating in frontal white matter corresponding to the NAA peak (r = 0.84, p < 0.001). The post-hoc analysis showed that the main NAA peak interval correlated negatively with the NAA in urine (r = -0.584, p < 0.001). CONCLUSION: The applied model and fitting free interval integration approach to analyse MRS data of a semi-LASER sequence at 3T suits well to detect and quantify pathological changes in MLD patients through the different courses of the disease and correlates well with clinical symptoms while showing smaller dimensions of variation compared to the more sophisticated single metabolite analysis using LCModel. NAA seems the most clinically meaningful biomarker to use in this context. Its correlation with urine measurements further underlines its potential as a clinically and biologically useful parameter of disease progression in MLD.

YNICL Journal 2022 Journal Article

Detection of spinal long fiber tract degeneration in HSP: Improved diffusion tensor imaging

  • Tobias Lindig
  • Christer Ruff
  • Tim W. Rattay
  • Stephan König
  • Ludger Schöls
  • Rebecca Schüle
  • Thomas Nägele
  • Ulrike Ernemann

Spinal diffusion tensor imaging (sDTI) is still a challenging technique for selectively evaluating anatomical areas like the pyramidal tracts (PT), dorsal columns (DC), and anterior horns (AH) in clinical routine and for reliably quantifying white matter anisotropy and diffusivity. In neurodegenerative diseases, the value of sDTI is promising but not yet well understood. The objective of this prospective, single-center study was to evaluate the long fiber tract degeneration within the spinal cord in normal aging (n = 125) and to prove its applicability in pathologic conditions as in patients with molecular genetically confirmed hereditary spastic paraplegias (HSP; n = 40), a prototypical disease of the first motor neuron and in some genetic variants with affection of the dorsal columns. An optimized monopolar Stejskal-Tanner sequence for high-resolution, axial sDTI of the cervical spinal cord at 3. 0 T with advanced standardized evaluation methods was developed for a robust DTI value estimation of PT, DC, and AH in both groups. After sDTI measurement at C2, an automatic motion correction and an advanced semi-automatic ROI-based, standardized evaluation of white matter anisotropy and diffusivity was performed to obtain regional diffusivity measures for PT, DC, and AH. Reliable and stable sDTI values were acquired in a healthy population without significant decline between age 20 and 65. Reference values for PT, DC, and AH for fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were established. In HSP patients, the decline of the long spinal fiber tracts could be demonstrated by diffusivity abnormalities in the pyramidal tracts with significantly reduced PTFA (p < 0. 001), elevated PTRD (p = 0. 002) and reduced PTMD (p = 0. 003) compared to healthy controls. Furthermore, FA was significantly reduced in DCFA (p < 0. 001) with no differences in AH. In a genetically homogeneous subgroup of SPG4 patients (n = 12) with affection of the dorsal columns, DCRD significantly correlated with the overall disease severity as measured by the Spastic Paraplegia Rating Scale (SPRS) (r = − 0. 713, p = 0. 009). With the most extensive sDTI study in vivo to date, we showed that axial sDTI combined with motion correction and advanced data post-processing strategies enables robust measurements and is ready to use, allowing recognition and quantification of disease- and age-related changes of the PT, DC, and AH. These results may also encourage the usage of sDTI in other neurodegenerative diseases with spinal cord involvement to explore its capability as selective biomarkers.

YNICL Journal 2019 Journal Article

Hypercapnic BOLD MRI compared to H215O PET/CT for the hemodynamic evaluation of patients with Moyamoya Disease

  • Till-Karsten Hauser
  • Achim Seeger
  • Benjamin Bender
  • Uwe Klose
  • Johannes Thurow
  • Ulrike Ernemann
  • Marcos Tatagiba
  • Philipp T. Meyer

BACKGROUND AND PURPOSE: O PET/CT with ACZ challenge to assess comparability between both modalities. METHODS: O PET/CT with ACZ challenge in patients with angiographically proven MMD. Images of both modalities were analyzed retrospectively in a blinded, standardized fashion by visual inspection, as well as with a semi-quantitative analysis using stimuli-induced approximated regional perfusion-weighted data and BOLD-signal changes with reference to cerebellum. RESULTS: 20 consecutive patients fulfilled the inclusion criteria, a total of 160 vascular territories were analyzed retrospectively. Visual analysis (4-step visual rating system) of standardized, color-coded cerebrovascular reserve/reactivity maps showed a very strong correlation (Spearman's rho = 0.9, P < 0.001) between both modalities. Likewise, comparison of approximated regional perfusion changes across vascular territories (normalized to cerebellar change) reveal a highly significant correlation between both methods (Pearson's r = 0.71, P < 0.001). CONCLUSIONS: O PET/CT with ACZ challenge. It therefore holds future potential in becoming a routine examination in the pre- and postoperative evaluation of MMD patients after further prospective evaluation.

YNIMG Journal 2018 Journal Article

Evaluation of multimodal segmentation based on 3D T1-, T2- and FLAIR-weighted images – the difficulty of choosing

  • Tobias Lindig
  • Raviteja Kotikalapudi
  • Daniel Schweikardt
  • Pascal Martin
  • Friedemann Bender
  • Uwe Klose
  • Ulrike Ernemann
  • Niels K. Focke

Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35. 8 years, 19–66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28. 1 years, 19–40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49. 0 years, 25–67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results.

YNICL Journal 2018 Journal Article

Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus

  • Benedikt Hofmeier
  • Stephan Wolpert
  • Ebrahim Saad Aldamer
  • Moritz Walter
  • John Thiericke
  • Christoph Braun
  • Dennis Zelle
  • Lukas Rüttiger

The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of the population, remains unknown and is controversial at many levels. It is an open question whether phantom sound perception results from increased central neural gain or not, a crucial question for any future therapeutic intervention strategies for tinnitus. We performed a comprehensive study of mild hearing-impaired participants with and without tinnitus, excluding participants with co-occurrences of hyperacusis. A right-hemisphere correlation between tinnitus loudness and auditory perceptual difficulty was observed in the tinnitus group, independent of differences in hearing thresholds. This correlation was linked to reduced and delayed sound-induced suprathreshold auditory brain responses (ABR wave V) in the tinnitus group, suggesting subsided rather than exaggerated central neural responsiveness. When anatomically predefined auditory regions of interest were analysed for altered sound-evoked BOLD fMRI activity, it became evident that subcortical and cortical auditory regions and regions involved in sound detection (posterior insula, hippocampus), responded with reduced BOLD activity in the tinnitus group, emphasizing reduced, rather than increased, central neural gain. Regarding previous findings of evoked BOLD activity being linked to positive connectivities at rest, we additionally analysed r-fcMRI responses in anatomically predefined auditory regions and regions associated with sound detection. A profound reduction in positive interhemispheric connections of homologous auditory brain regions and a decline in the positive connectivities between lower auditory brainstem regions and regions involved in sound detection (hippocampus, posterior insula) were observed in the tinnitus group. The finding went hand-in-hand with the emotional (amygdala, anterior insula) and temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal gyrus) that were no longer positively connected with auditory cortex regions in the tinnitus group but were instead positively connected to lower-level auditory brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus group and showed right hemisphere dominance as did tinnitus loudness and perceptual difficulty. The findings suggest that reduced central neural gain in the auditory stream may lead to phantom perception through a failure to energize attentional/stress-regulating networks for contextualization of auditory-specific information. Reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies. TRIAL REGISTRATION: German Clinical Trials Register DRKS0006332.

YNIMG Journal 2005 Journal Article

Single-shot compensation of image distortions and BOLD contrast optimization using multi-echo EPI for real-time fMRI

  • Nikolaus Weiskopf
  • Uwe Klose
  • Niels Birbaumer
  • Klaus Mathiak

Functional magnetic resonance imaging (fMRI) is most commonly based on echo-planar imaging (EPI). With higher field strengths, gradient performance, and computational power, real-time fMRI has become feasible; that is, brain activation can be monitored during the ongoing scan. However, EPI suffers from geometric distortions due to inhomogeneities of the magnetic field, especially close to air–tissue interfaces. Thus, functional activations might be mislocalized and assigned to the wrong anatomical structures. Several techniques have been reported which reduce geometric distortions, for example, mapping of the static magnetic field B0 or the point spread function for all voxels. Yet these techniques require additional reference scans and in some cases extensive computational time. Moreover, only static field inhomogeneities can be corrected, because the correction is based on a static reference scan. We present an approach which allows for simultaneous acquisition and distortion correction of a functional image without a reference scan. The technique is based on a modified multi-echo EPI data acquisition scheme using a phase-encoding (PE) gradient with alternating polarity. The images exhibit opposite distortions due to the inverted PE gradient. After adjusting the contrast of the images acquired at different echo times, this information is used for the distortion correction. We present the theory, implementation, and applications of this single-shot distortion correction. Significant reduction in geometric distortion is shown both for phantom images and human fMRI data. Moreover, sensitivity to the blood oxygen level-dependent (BOLD) effect is increased by weighted summation of the undistorted images.

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