Biology subjects

Doerfler, A.

Publications and source records attributed to Doerfler, A..

7 recordsLinked to original sources

bioRxiv2026

The Mechanical Fingerprint of Hippocampal Sclerosis Linking Neuronal Cell Loss and Gliosis to Tissue Stiffness

Hippocampal sclerosis (HS) is the most common pathology in drug-resistant temporal lobe epilepsy (TLE). However, clinical diagnosis, prevalent epileptogenicity, and drug drug-resistance in individuals with HS remain an ongoing challenge demanding multidisciplinary research efforts. In this study, we examined the mechanical properties of neurosurgically en bloc resected HS specimens (n=8) ex vivo under compression, tension, and torsional shear. We fitted a two-term Ogden hyperelastic model to the measured mechanical responses to quantify nonlinear mechanical tissue properties. The resulting parameters revealed higher strain stiffening under compression in HS compared to hippocampus obtained post mortem (n=7). The distinction was most noticeable in the large-strain regime, which has important implications for using mechanical tissue properties as valuable diagnostic biomarker. Furthermore, we correlated the tissue microstructure with mechanical parameters. We trained a deep-learning histopathology classifier to detect and classify neurons and glial cells from hematoxylin-stained whole slide images (WSI). We identified a strong association between the small-strain stiffness (shear modulus {micro}) and the overall cell density as well as the glial cell density. The negative relationship between the neuron-to-glia ratio and shear modulus is consistent with the hypothesis that neuronal cell loss and gliosis drives tissue stiffening, respectively. Magnetic resonance imaging (MRI) analysis of the specimens confirmed the previously reported negative association between MRI-derived fractional anisotropy and shear modulus {micro}. Taken together, our study establishes a direct link between tissue mechanics and microstructure, suggesting nonlinear continuum mechanics models as promising new tools for clinical diagnosis and novel research strategies.

bioengineering↗

bioRxiv2026

Towards patient-specific biomechanical human brain models

Reliable characterization of spatial variations in brain tissue stiffness is essential for predictive biomechanical modeling, yet most current methods rely on coarse regional parameter assignments based on invasive mechanical testing. In this study, we propose a new approach to obtain subject-specific mechanical properties at voxel resolution from in vivo diffusion tensor magnetic resonance imaging (DTI) based on a linear regression between the fractional anisotropy (FA) from DTI and experimentally measured stiffness values. To assess how such heterogeneity in mechanical properties influences simulated brain deformation, we construct a finite element model based on two material parameterizations of the same human brain: one employing nine anatomically defined regions, each with uniform material parameters, and another in which the shear modulus is assigned voxel-wise on the corresponding FA value. Applying this FA-stiffness mapping yields a smoothly varying mechanical property distribution that better captures local microstructural differences not represented by region-wise parameterizations. Both parameterizations are subjected to an identical atrophy-driven loading scenario. They exhibit comparable overall volume loss, but diverge in regional behavior. The voxel-resolved parameterization predicts more pronounced ventricular expansion and differs in the displacement and stretch distributions, indicating that variability in stiffness can alter local predicted responses even when global outcomes appear similar. This work presents a pipeline for estimating individualized mechanical properties directly from imaging protocols that are routinely performed on patients, with important implications for brain biomechanics. While the approach depends on a simplified linear FA-stiffness relation and assumes isotropic constitutive behavior, it provides a framework for integrating imaging-based microstructure into subject-specific simulations. Future validation against in vivo or experimental deformation data is needed to determine the fidelity and clinical utility of FA-derived stiffness fields.

neuroscience↗

bioRxiv2026

Fractional Anisotropy as a Surrogate Marker of Brain Mechanics

Understanding the mechanical properties of brain tissue may provide crucial insights into brain development, injury, disease and surgical planning. Conventionally, these properties are measured ex vivo or in vivo during surgical procedures, while non-invasive in vivo alternatives are sparse. This study investigates whether fractional anisotropy (FA) derived from diffusion-weighted magnetic resonance imaging can serve as a surrogate marker for brain tissue stiffness in healthy human brains. MRI data were collected from three body donor brains, 28 healthy adults, and a publicly available independent dataset of 26 adults. FA values were compared with mechanical properties from ex vivo mechanical testing of brain tissue. Statistical analysis revealed a strong negative correlation between FA and the mechanical response for small strains expressed as shear modulus of a one-term hyperelastic Ogden model, indicating that higher FA values are associated with lower tissue stiffness. The nonlinearity parameter alpha exhibited a qualitatively similar, but considerably weaker correlation with FA. These findings were consistent across datasets. The findings suggest that FA can be a robust, non-invasive marker for estimating mechanical properties of brain tissue, with potential applications in clinical diagnosis and computational modeling of brain mechanics and the study of brain development. Further research is needed to clarify the relationship in lesional tissues and to optimize clinical utility.

neuroscience↗

bioRxiv2025

CRYO-CEST: Non-invasive imaging of cryoprotectants using chemical exchange saturation transfer

Chemical exchange saturation transfer (CEST) MRI at 7T was explored as a non-invasive method to detect and quantify common cryoprotectants used in organ cryopreservation. Phantom experiments demonstrated clear CEST signals from ethylene glycol, formamide, and dimethyl sulfoxide, with formamide showing the most sensitive concentration-dependent response. CEST imaging could thus provide a practical tool for monitoring cryoprotectant concentrations in organs.

biophysics↗

bioRxiv2025

Spatiotemporal Patterns Differentiate Hippocampal Sharp-Wave Ripples from Interictal Epileptiform Discharges in Mice and Humans

Hippocampal sharp-wave ripples (SPW-Rs) are high-frequency oscillations critical for memory consolidation in mammals. Despite extensive characterization in rodents, their application as biomarkers to track and treat memory dysfunction in humans is limited by coarse spatial sampling, interference from interictal epileptiform discharges (IEDs), and lack of consensus on human SPW-R localization and morphology. We demonstrate that mouse and human hippocampal ripples share spatial, spectral and temporal features, which are clearly distinct from IEDs. In 1024-channel hippocampal recordings from APP/PS1 mice, SPW-Rs were distinguishable from IEDs by their narrow localization to the CA1 pyramidal layer, narrowband frequency peaks, and multiple ripple cycles on the unfiltered local field potential. In epilepsy patients, ripples showed similar narrowband frequency peaks and visible ripple cycles in CA1 and the subiculum but were absent in the dentate gyrus. Conversely, IEDs showed a broad spatial extent and wide-band frequency power. We introduce a semi-automated, human ripple detection toolbox ("ripmap") selecting optimal detection channels and separating event waveforms by low-dimensional embedding. Our approach improves ripple detection accuracy, providing a firm foundation for future human memory research.

neuroscience↗

bioRxiv2022

Capturing early human memory consolidation utilizing the higher functional specificity of 7T compared to 3T-fMRI

Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the BOLD response to distinct neuronal processes continues to be challenging. Here, we performed 3T and 7T-fMRI analysis of motor-task activation and resting-state connectivity with adjusted SNR. We then applied graph theory to analyze resting-state neuronal networks detected by fMRI after a simple motor task. Despite adjusted SNR, 7T achieved a higher functional specificity of the BOLD response than 3T-fMRI. Following the motor task, 7T-fMRI therefore enabled the detection of an offline replay that was directly linked to brain regions associated with memory consolidation. These findings reveal how memory processing is initiated even after simple motor tasks and begins earlier than previously shown. Thus, the superior capability of 7T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.

neuroscience↗

bioRxiv2018

Neural mechanisms of perceptive and affective processing of body stimuli in Anorexia nervosa - are there developmental effects?

ObjectiveDifferent components of body image processing seem to be reflected by different neural mechanisms. A core symptom of Anorexia nervosa (AN) is a disturbance of body image with correlates found on a neural level. The present study focusses at the neural processing of visual body stimuli of different weight categories in adolescent and adult AN patients.\n\nMethod33 adolescents aged 12-18 years (15 AN patients, 18 control participants) and 36 adult women (19 AN patients, 17 control participants) underwent functional magnetic resonance imaging (fMRI) while performing a perceptive and an affective body image task involving photographic stimuli of women belonging to different BMI categories.\n\nResultsDifferential effects on activation depending on the BMI of the women shown in the pictures were found in frontal brain regions, the thalamus, caudate and the fusiform gyrus. Group effects differentiating between AN patients and control participants were seen mainly in the caudate and insula.\n\nDiscussionDuring a perceptive task, diminished activation of regions involved in perceptive and evaluative functions as well as emotional reasoning was seen in AN. During evaluation of the neural processing in an affective task there was a tendency towards activation differences reflecting reduced ability of size estimation and impaired integration of visual and body perception with emotions.

neuroscience↗