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Philipp T. Meyer

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8

YNICL Journal 2024 Journal Article

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

  • Bastian E.A. Sajonz
  • Marvin L. Frommer
  • Marco Reisert
  • Ganna Blazhenets
  • Nils Schröter
  • Alexander Rau
  • Thomas Prokop
  • Peter C. Reinacher

BACKGROUND: Thalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. METHODS: F]Fluorodeoxyglucose positron emission tomography were applied. RESULTS: = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. CONCLUSION: Our results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

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YNICL Journal 2022 Journal Article

Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? – Additional clinical and neuroimaging evidence

  • Bastian E.A. Sajonz
  • Marvin L. Frommer
  • Isabelle D. Walz
  • Marco Reisert
  • Christoph Maurer
  • Michel Rijntjes
  • Tobias Piroth
  • Nils Schröter

BACKGROUND: Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. OBJECTIVE: Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. METHODS: F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. RESULTS: compared with the healthy controls. CONCLUSIONS: Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.

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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.

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YNICL Journal 2018 Journal Article

Voxel-wise deviations from healthy aging for the detection of region-specific atrophy

  • Stefan Klöppel
  • Shan Yang
  • Elias Kellner
  • Marco Reisert
  • Bernhard Heimbach
  • Horst Urbach
  • Jennifer Linn
  • Stefan Weidauer

The identification of pathological atrophy in MRI scans requires specialized training, which is scarce outside dedicated centers. We sought to investigate the clinical usefulness of computer-generated representations of local grey matter (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations (z-scores) from healthy aging to either aid human visual readings or directly detect pathological atrophy. Two experienced neuroradiologists rated atrophy in 30 patients with Alzheimer's disease (AD), 30 patients with frontotemporal dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy controls (HC) on a three-point scale in 10 anatomical regions as reference gold standard. Seven raters, varying in their experience with MRI diagnostics rated all cases on the same scale once with and once without computer-generated volume deviation maps that were overlaid on anatomical slices. In addition, we investigated the predictive value of the computer generated deviation maps on their own for the detection of atrophy as identified by the gold standard raters. Inter and intra-rater agreements of the two gold standard raters were substantial (Cohen's kappa κ > 0.62). The intra-rater agreement of the other raters ranged from fair (κ = 0.37) to substantial (κ = 0.72) and improved on average by 0.13 (0.57 < κ < 0.87) when volume deviation maps were displayed. The seven other raters showed good agreement with the gold standard in regions including the hippocampus but agreement was substantially lower in e.g. the parietal cortex and did not improve with the display of atrophy scores. Rating speed increased over the course of the study and irrespective of the presentation of voxel-wise deviations. Automatically detected large deviations of local volume were consistently associated with gold standard atrophy reading as shown by an area under the receiver operator characteristic of up to 0.95 for the hippocampus region. When applying these test characteristics to prevalences typically found in a memory clinic, we observed a positive or negative predictive value close to or above 0.9 in the hippocampus for almost all of the expected cases. The volume deviation maps derived from CSF volume increase were generally better in detecting atrophy. Our study demonstrates an agreement of visual ratings among non-experts not further increased by displaying, region-specific deviations of volume. The high predictive value of computer generated local deviations independent from human interaction and the consistent advantages of CSF-over GM-based estimations should be considered in the development of diagnostic tools and indicate clinical utility well beyond aiding visual assessments.

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YNIMG Journal 2010 Journal Article

Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses

  • Philipp T. Meyer
  • Zubin Bhagwagar
  • Philip J. Cowen
  • Vincent J. Cunningham
  • Paul M. Grasby
  • Rainer Hinz

Background: [11C]MDL100, 907 is a promising positron emission tomography (PET) ligand for 5-HT2A receptor quantification in vivo. Studies suggest that [11C]MDL100, 907 PET may be quantified by non-invasive reference tissue analyses using cerebellum as reference region. We systematically investigated the validity of such analyses. Methods: Five healthy volunteers underwent [11C]MDL100, 907 PET at baseline and after mirtazapine pre-treatment. Regional time–activity curves of 10 regions of interest (ROI) were analyzed for binding potential (BP ND) and mirtazapine receptor occupancy (Occ) using: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2), non-invasive graphical analysis (NIGA) and a tissue activity concentration ratio. NIGA was also applied voxel-wise to generate BP ND maps. These methods were compared with a two-tissue compartment model with arterial input function (2TCM) Results: SRTM and MRTM frequently failed to yield reliable results. SRTM2 and MRTM2 gave virtually identical estimates of BP ND, which were highly correlated with 2TCM analyses (R 2 ≥0. 86) although with negative bias (−29±27% at baseline across all ROI). NIGA was less biased (−19±16%) and better correlated with 2TCM (R 2 ≥0. 93). Regarding Occ, NIGA and SRTM2/MRTM2 showed comparable mean biases (−11±27% vs. −7±47%) but correlation with 2TCM was higher for NIGA (R 2 =0. 90 vs. 0. 77). NIGA parametric maps (analysed using identical ROI) resulted in moderate bias in BP ND (−26±22%; R 2 ≥0. 88) and Occ (−17±36%; R 2 =0. 78). Estimates obtained from tissue ratios performed least favourably. Conclusions: NIGA is well suited for analysis of [11C]MDL100, 907 PET studies, yielding estimates of 5-HT2A receptor availability and changes that are highly correlated with results from invasive 2TCM analyses. This should greatly enhance the applicability of 5-HT2A receptor PET studies.

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