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Mona K. Beyer

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3 papers

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YNICL Journal 2022 Journal Article

Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study

Henning H. Rise
Synne Brune
Claudia Chien
Tone Berge
Steffan D. Bos
Magí Andorrà
Irene Pulido Valdeolivas
Mona K. Beyer

BACKGROUND AND OBJECTIVES: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. METHODS: MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. RESULTS: ), and longitudinal changes in NfL (t = -2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). DISCUSSION: In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.

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YNIMG Journal 2016 Journal Article

Power estimation for non-standardized multisite studies

Anisha Keshavan
Friedemann Paul
Mona K. Beyer
Alyssa H. Zhu
Nico Papinutto
Russell T. Shinohara
William Stern
Michael Amann

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions.

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YNIMG Journal 2009 Journal Article

White matter hyperintensities do not impact cognitive function in patients with newly diagnosed Parkinson's disease

Turi O. Dalaker
Jan P. Larsen
Michael G. Dwyer
Dag Aarsland
Mona K. Beyer
Guido Alves
Kolbjorn Bronnick
Ole-Bjorn Tysnes

The objective of this study was to investigate total volume and spatial distribution of white matter hyperintensities (WMH) in a large sample of newly diagnosed Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI) compared to normal controls (NC). Furthermore, we aimed to examine the impact of the WMH on attention–executive performance in PD. MCI is regarded as a pre-dementia stage. Studies on MCI have found WMH associated with reduced cognitive function, especially in the attention and executive domains. The present study included 163 incident, drug-naïve PD patients (66. 2±9. 1 years and disease duration 27. 1±19. 8 months) and 102 age-matched NC (65. 7±9. 4 years). Thirty (30) subjects in the PD sample presented MCI, whereas 133 did not. MCI was classified based on tests for memory, attention–executive and visuospatial function compared to the NC group, taking age, sex and education into consideration. WMH were outlined on FLAIR scans using a semi-automated technique. Total WMH volumes were compared between the 3 study groups, and spatial distribution of normalized WMH masks in each group were compared using voxel-wise probability maps. Regression analysis examined the possible impact of WMH on attention–executive scores in the PD group. Analysis showed that there were no significant differences between the 3 groups in total volume or spatial distribution of WMH. In addition there was no significant relationship between total volume or spatial distribution of WMH and attention–executive functions in PD. We conclude that in this PD cohort, cognitive impairment seems to be independent of WMH damage.

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