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Jens Wuerfel

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12 papers

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YNICL Journal 2026 Journal Article

Microstructure-informed deep learning improves thalamic atrophy segmentation and clinical associations in multiple sclerosis and related neuroimmunological diseases

Omar Angelo Ibrahim
Henri Trang
Qianlan Chen
Lara Zimmermann
Alexander U. Brandt
Tatiana Usnich
Stefano Magon
Muhamed Barakovic

Thalamic atrophy is a sensitive imaging marker of neurodegeneration in multiple sclerosis (MS) and related disorders, though thalamus segmentation remains method-dependent. Quantitative magnetic resonance imaging (qMRI) may enhance thalamic boundary contrast, particularly in the context of deep learning. We benchmarked thalamic segmentations from two atlas-constrained algorithms, FreeSurfer and FIRST, and two deep learning algorithms, DBSegment and MindGlide (an MS-trained model), against ground truth (GT) labels, tested whether quantitative R1 maps improve performance, and evaluated clinical validity cross-sectionally and longitudinally. We generated thalamus masks using each algorithm from T1-weighted data in a single-scanner cohort (baseline n = 321; 1-year follow-up n = 234) including patients with MS/related disorders and healthy controls. Using MindGlide, we also produced FLAIR- and R1-based masks and ensembles. Manual GT labels were obtained for 50 MS patients using T1w and FLAIR scans. For voxel-wise GT agreement, DBSegment yielded the highest Dice-similarity coefficient; atlas-constrained methods showed the highest sensitivity but lowest precision, while MindGlide balanced both. Volumetrically, MindGlide showed the most accurate estimates; DBSegment and FreeSurfer showed proportional bias, and both atlas-constrained methods overestimated thalamic volumes. Adding R1 input to MindGlide produced modest or no gains in GT agreement. Additionally, MindGlide volumes were most consistently associated with disability and cognitive scores cross-sectionally, and longitudinally showed the largest effects between thalamic volume change and EDSS worsening. Incorporating R1 maps offered no cross-sectional benefit but strengthened longitudinal associations. Higher-resolution qMRI and multi-contrast deep learning architectures may further enhance thalamic segmentation and monitoring in neuroinflammatory diseases.

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YNICL Journal 2022 Journal Article

Brain atrophy measurement over a MRI scanner change in multiple sclerosis

Tim Sinnecker
Sabine Schädelin
Pascal Benkert
Esther Ruberte
Michael Amann
Johanna M. Lieb
Yvonne Naegelin
Jannis Müller

BACKGROUND: A change in MRI hardware impacts brain volume measurements. The aim of this study was to use MRI data from multiple sclerosis (MS) patients and healthy control subjects (HCs) to statistically model how to adjust brain atrophy measures in MS patients after a major scanner upgrade. METHODS: We scanned 20 MS patients and 26 HCs before and three months after a major scanner upgrade (1.5 T Siemens Healthineers Magnetom Avanto to 3 T Siemens Healthineers Skyra Fit). The patient group also underwent standardized serial MRIs before and after the scanner change. Percentage whole brain volume changes (PBVC) measured by Structural Image Evaluation using Normalization of Atrophy (SIENA) in the HCs was used to estimate a corrective term based on a linear model. The factor was internally validated in HCs, and then applied to the MS group. RESULTS: Mean PBVC during the scanner change was higher in MS than HCs (-4.1 ± 0.8 % versus -3.4 ± 0.6 %). A fixed corrective term of 3.4 (95% confidence interval: 3.13-3.67)% was estimated based on the observed average changes in HCs. Age and gender did not have a significant influence on this corrective term. After adjustment, a linear mixed effects model showed that the brain atrophy measures in MS during the scanner upgrade were not anymore associated with the scanner type (old vs new scanner; p = 0.29). CONCLUSION: A scanner change affects brain atrophy measures in longitudinal cohorts. The inclusion of a corrective term based on changes observed in HCs helps to adjust for the known and unknown factors associated with a scanner upgrade on a group level.

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YNICL Journal 2022 Journal Article

Longitudinal changes of deep gray matter shape in multiple sclerosis

Charidimos Tsagkas
Emanuel Geiter
Laura Gaetano
Yvonne Naegelin
Michael Amann
Katrin Parmar
Athina Papadopoulou
Jens Wuerfel

OBJECTIVE: This study aimed to investigate longitudinal deep gray matter (DGM) shape changes and their relationship with measures of clinical disability and white matter lesion-load in a large multiple sclerosis (MS) cohort. MATERIALS AND METHODS: A total of 230 MS patients (179 relapsing-remitting, 51 secondary progressive; baseline age 44.5 ± 11.3 years; baseline disease duration 12.99 ± 9.18) underwent annual clinical and MRI examinations over a maximum of 6 years (mean 4.32 ± 2.07 years). The DGM structures were segmented on the T1-weighted images using the "Multiple Automatically Generated Templates" brain algorithm. White matter lesion-load was measured on T2-weighted MRI. Clinical examination included the expanded disability status scale, 9-hole peg test, timed 25-foot walk test, symbol digit modalities test and paced auditory serial addition test. Vertex-wise longitudinal analysis of DGM shapes was performed using linear mixed effect models and evaluated the association between average/temporal changes of DGM shapes with average/temporal changes of clinical measurements, respectively. RESULTS: A significant shrinkage over time of the bilateral ventrolateral pallidal and the left posterolateral striatal surface was observed, whereas no significant shape changes over time were observed at the bilateral thalamic and right striatal surfaces. Higher average lesion-load was associated with an average inwards displacement of the global thalamic surface with relative sparing on the posterior side (slight left-side predominance), the antero-dorso-lateral striatal surfaces bilaterally (symmetric on both sides) and the antero-lateral pallidal surface (left-side predominance). There was also an association between shrinkage of large lateral DGM surfaces with higher clinical motor and cognitive disease severity. However, there was no correlation between any DGM shape changes over time and measurements of clinical progression or lesion-load changes over time. CONCLUSIONS: This study showed specific shape change of DGM structures occurring over time in relapse-onset MS. Although these shape changes over time were not associated with disease progression, we demonstrated a link between DGM shape and the patients' average disease severity as well as white matter lesion-load.

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YNIMG Journal 2021 Journal Article

A contrast-adaptive method for simultaneous whole-brain and lesion segmentation in multiple sclerosis

Stefano Cerri
Oula Puonti
Dominik S. Meier
Jens Wuerfel
Mark Mühlau
Hartwig R. Siebner
Koen Van Leemput

Here we present a method for the simultaneous segmentation of white matter lesions and normal-appearing neuroanatomical structures from multi-contrast brain MRI scans of multiple sclerosis patients. The method integrates a novel model for white matter lesions into a previously validated generative model for whole-brain segmentation. By using separate models for the shape of anatomical structures and their appearance in MRI, the algorithm can adapt to data acquired with different scanners and imaging protocols without retraining. We validate the method using four disparate datasets, showing robust performance in white matter lesion segmentation while simultaneously segmenting dozens of other brain structures. We further demonstrate that the contrast-adaptive method can also be safely applied to MRI scans of healthy controls, and replicate previously documented atrophy patterns in deep gray matter structures in MS. The algorithm is publicly available as part of the open-source neuroimaging package FreeSurfer.

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YNICL Journal 2021 Journal Article

Lateral geniculate nucleus volume changes after optic neuritis in neuromyelitis optica: A longitudinal study

Athina Papadopoulou
Frederike C. Oertel
Claudia Chien
Joseph Kuchling
Hanna G. Zimmermann
Nadja Siebert
Seyedamirhosein Motamedi
Marcus D' Souza

OBJECTIVES: Lateral geniculate nucleus (LGN) volume is reduced after optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD). We aimed at a longitudinal assessment of LGN volume in NMOSD. METHODS: Twenty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 47.8 ± 14.6 years (y), female: n = 27, history of ON (NMO-ON): n = 17, median time since ON: 3[1.2-12.1]y) and 18 healthy controls (HC; age: 39.3 ± 15.8y; female: n = 13) were included. Median follow-up was 4.1[1.1-4.7]y for patients and 1.7[0.9-3.2]y for HC. LGN volume was measured using a multi-atlas-based approach of automated segmentation on 3 Tesla magnetic resonance images. Retinal optical coherence tomography and probabilistic tractography of the optic radiations (OR) were also performed. RESULTS: ; t = -3.6, p = 0.036). CONCLUSION: Although LGN volume is reduced after ON in NMOSD, this volume loss is not progressive over longer follow-up or independent of ON. Thus, our findings -at least in this relatively small cohort- do not support occult neurodegeneration of the afferent visual pathway in NMOSD.

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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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YNIMG Journal 2019 Journal Article

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study

Anna Altermatt
Laura Gaetano
Stefano Magon
Lorena Bauer
Regina Feurer
Hans Gnahn
Julia Hartmann
Christian L. Seifert

Background Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. Aim The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. Methods 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0. 05). Results A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68. 2 ± 7. 6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0. 001), and a worse performance in some of the cognitive subdomain scores (p < 0. 05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants’ total lesion burden (p < 0. 05), no focal WMH locations were found to be associated with cognitive impairment. Conclusion Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults.

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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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YNICL Journal 2015 Journal Article

MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis

Martin Weygandt
Hannah-Maria Hummel
Katharina Schregel
Kerstin Ritter
Carsten Allefeld
Esther Dommes
Peter Huppke
JohnDylan Haynes

Currently, it is unclear whether pediatric multiple sclerosis (PMS) is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS). Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM) and white matter (WM) tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12 years), LOPMS patients (onset ≥12 years), and healthy controls (HC). This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p < 2.2 × 10(-5)). MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p = 1.8 × 10(-4)). Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed.

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YNIMG Journal 2010 Journal Article

MR-elastography reveals degradation of tissue integrity in multiple sclerosis

Jens Wuerfel
Friedemann Paul
Bernd Beierbach
Uwe Hamhaber
Dieter Klatt
Sebastian Papazoglou
Frauke Zipp
Peter Martus

In multiple sclerosis (MS), diffuse brain parenchymal damage exceeding focal inflammation is increasingly recognized to be present from the very onset of the disease, and, although occult to conventional imaging techniques, may present a major cause of permanent neurological disability. Subtle tissue alterations significantly influence biomechanical properties given by stiffness and internal friction, that – in more accessible organs than the brain – are traditionally assessed by manual palpation during the clinical exam. The brain, however, is protected from our sense of touch, and thus our current knowledge on cerebral viscoelasticity is very limited. We developed a clinically feasible magnetic resonance elastography setup sensitive to subtle alterations of brain parenchymal biomechanical properties. Investigating 45 MS patients revealed a significant decrease (13%, P <0. 001) of cerebral viscoelasticity compared to matched healthy volunteers, indicating a widespread tissue integrity degradation, while structure-geometry defining parameters remained unchanged. Cerebral viscoelasticity may represent a novel in vivo marker of neuroinflammatory and neurodegenerative pathology.

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YNIMG Journal 2009 Journal Article

Targeting activated microglia in Alzheimer's pathology by intraventricular delivery of a phagocytosable MRI contrast agent in APP23 transgenic mice

Adrian P. Mundt
Christine Winter
Susanne Mueller
Jens Wuerfel
Eva Tysiak
Jörg Schnorr
Matthias Taupitz
Andreas Heinz

The role of phagocytosing immune cells in Alzheimer's pathology can be studied experimentally in APP23 transgenic mice. This present study intended to label phagocytosing immune cells in the plaque periphery of APP23 mice in vivo by intraventricular injection of VSOP-C184, a phagocytosable iron oxide nanoparticle MRI contrast agent. Firstly, the dosages of 0. 1, 1. 0 and 10 μmol Fe/kg body weight dissolved in 500 nl of artificial cerebrospinal fluid, delivered by stereotaxic surgery were evaluated 4 h after surgery in 7 wild type mice using 7 T MRI. Secondly, the dosage of 1. 0 μmol Fe/kg body weight was investigated in 6 APP23 mice. The distribution of iron oxide particles was evaluated histologically. The injection of 0. 1 μmol Fe/kg body weight did not result in any signal alterations, 10 μmol resulted in strong signal artifacts. The delivery of 1. 0 μmol Fe/kg body weight in wild type mice resulted in MRI signal alterations throughout the ventricular system without large artifacts. It was regarded superior to other dosages for the study of the transgenic mice. There was no difference in MRI signal alterations and the distribution of iron particles in the histology between APP23 and wild type mice using the dosage of 1. 0 μmol Fe/kg body weight. Upon intraventricular injection, the phagocytosable contrast agent VSOP-C184 distributes throughout the ventricular system, whereas it does not reach the periphery of amyloid plaques in APP23 mice in a concentration sufficient to cause MRI signal alterations.

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YNIMG Journal 2009 Journal Article

The impact of aging and gender on brain viscoelasticity

Ingolf Sack
Bernd Beierbach
Jens Wuerfel
Dieter Klatt
Uwe Hamhaber
Sebastian Papazoglou
Peter Martus
Jürgen Braun

Viscoelasticity is a sensitive measure of the microstructural constitution of soft biological tissue and is increasingly used as a diagnostic marker, e. g. in staging liver fibrosis or characterizing breast tumors. In this study, multifrequency magnetic resonance elastography was used to investigate the in vivo viscoelasticity of healthy human brain in 55 volunteers (23 females) ranging in age from 18 to 88 years. The application of four vibration frequencies in an acoustic range from 25 to 62. 5 Hz revealed for the first time how physiological aging changes the global viscosity and elasticity of the brain. Using the rheological springpot model, viscosity and elasticity are combined in a parameter μ that describes the solid-fluid behavior of the tissue and a parameter α related to the tissue's microstructure. It is shown that the healthy adult brain undergoes steady parenchymal ‘liquefaction’ characterized by a continuous decline in μ of 0. 8% per year (P <0. 001), whereas α remains unchanged. Furthermore, significant sex differences were found with female brains being on average 9% more solid-like than their male counterparts rendering women more than a decade ‘younger’ than men with respect to brain mechanics (P =0. 016). These results set the background for using cerebral multifrequency elastography in diagnosing subtle neurodegenerative processes not detectable by other diagnostic methods.

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