Search bioRxiv⌕ Search

Biology subjects

Dahnke, R.

Publications and source records attributed to Dahnke, R..

8 recordsLinked to original sources

ComCat: Combating Covariate Effects in Brain Analysis

As neuroimaging analysis shifts toward large-scale, multi-site studies, managing the unwanted variability introduced by combining heterogeneous datasets has become a critical challenge. Although tools such as ComBat and its neuroimaging extensions are widely used to address this variability, they only permit the modeling of categorical site effects and cannot account for continuous sources of confounding, such as image quality, head motion, and acquisition parameters. We introduce ComCat, an extension of the ComBat framework that preserves biologically relevant covariates while removing the effects of categorical site indicators and continuous nuisance variables. The latter are modeled as smooth nonlinear functions via B-spline basis expansion. ComCat is applicable to a broad range of brain analysis tasks, including voxel- and surface-based morphometry, normative modeling, and machine learning-based prediction. To demonstrate its capabilities, we evaluated ComCat on brain age prediction across five datasets covering complementary multi-site harmonization scenarios: ON-Harmony (10 subjects x 6 scanners; n = 80); the Buchert traveling-phantom dataset (1 subject x 116 scanners; n = 531); the Tohoku single-scanner, varying-acquisition dataset (n = 121); MR-ART (148 subjects with varying motion levels); and an ABIDE subset comprising 229 control subjects and 208 individuals with autism spectrum disorder across 14 scanners. Using image quality measures derived from CAT12 as continuous nuisance variables, ComCat reduced the mean absolute error (MAE) in brain age prediction relative to ComBat-GAM in all five datasets, including the two scenarios where site information was unavailable or uninformative. In the ABIDE dataset, ComCat improved harmonization while preserving the difference between the control and ASD groups, demonstrating that scanner-related variance can be removed without affecting biologically meaningful signals. ComCat can operate with or without site labels and is agnostic to the source of image quality metrics.

neuroscience↗

The Good, the Bad, and the Ugly: Segmentation-Based Quality Control of Structural Magnetic Resonance Images

The processing and analysis of magnetic resonance images is highly dependent on the quality of the input data, and systematic differences in quality can consequently lead to loss of sensitivity or biased results. However, varying image properties due to different scanners and acquisition protocols, as well as subject-specific image interferences, such as motion artifacts, can be incorporated in the analysis. A reliable assessment of image quality is therefore essential to identify critical outliers that may bias results. Here we present a quality assessment for structural (T1-weighted) images using tissue classification. We introduce multiple useful image quality measures, standardize them into quality scales and combine them into an integrated structural image quality rating to facilitate the interpretation and fast identification of outliers with (motion) artifacts. The reliability and robustness of the measures are evaluated using synthetic and real datasets. Our study results demonstrate that the proposed measures are robust to simulated segmentation problems and variables of interest such as cortical atrophy, age, sex, brain size and severe disease-related changes, and might facilitate the separation of motion artifacts based on within-protocol deviations. The quality control framework presents a simple but powerful tool for the use in research and clinical settings.

neuroscience↗

Approximation of bone mineral density and subcutaneous adiposity using T1-weighted images of the human head

Bones and brain are intricately connected and scientific interest in their interaction is growing. This has become particularly evident in the framework of clinical applications for various medical conditions, such as obesity and osteoporosis. The adverse effects of obesity on brain health have long been recognised, but few brain imaging studies provide sophisticated body composition measures. Here we propose to extract the following bone- and adiposity-related measures from T1-weighted MR images of the head: an approximation of skull bone mineral density (BMD), skull bone thickness, and two approximations of subcutaneous fat (i.e., the intensity and thickness of soft non-brain head tissue). The measures pertaining to skull BMD, skull bone thickness, and intensi-ty-based adiposity proxy proved to be reliable (r=.93/.83/.74, p<.001) and valid, with high correlations to DXA-de-rived head BMD values (rho=.70, p<.001) and MRI-derived abdominal subcutaneous adipose volume (rho=.62, p<.001). Thickness-based adiposity proxy had only a low retest reliability (r=.58, p<.001).The outcomes of this study constitute an important step towards extracting relevant non-brain features from available brain scans.

neuroscience↗

BrainAGE revisited: Keeping up the pace with deep learning methods

Since the introduction of the BrainAGE method (Franke et al., 2010), novel machine learning methods of brain age prediction have continued to emerge. The idea of estimating the chronological age from magnetic resonance images proved to be an interesting field of research due to the relative simplicity of its interpretation and its potential use as a biomarker of brain health. We revised our previous BrainAGE approach, originally utilising relevance vector regression (RVR), and substituted it with Gaussian process regression (GPR), which enables more stable processing of larger datasets, such as the UK Biobank (UKB). In addition, we extended the global BrainAGE approach to regional BrainAGE, providing spatially specific scores for 5 brain lobes per hemisphere. We tested the performance of the new algorithms under several different conditions and investigated their validity on the ADNI and schizophrenia samples, as well as on a synthetic dataset of neocortical thinning. The results show an improved performance of the reframed global model on the UKB sample with a mean absolute error (MAE) of less than 2 years and a significant difference in BrainAGE between healthy participants and patients with Alzheimers disease and schizophrenia. Moreover, the workings of the algorithm show meaningful effects for a simulated neocortical atrophy dataset. The regional BrainAGE model performed well on two clinical samples, showing disease-specific patterns for different levels of impairment. The results demonstrate that the new improved algorithms provide reliable and valid brain age estimations.

neuroscience↗

The Uniqueness of Human Vulnerability to Brain Aging in Great Ape Evolution

Aging is associated with robust decline of the brains gray matter. This spatially specific, morphological change in humans has recently been found in chimpanzees. Direct comparison of age-related brain deterioration between these great ape species can provide a unique evolutionary perspective on human brain aging. Here, we present a data-driven, cross-species comparative framework to explore the relationship between gray matter atrophy with age and cross-species cerebral expansion in chimpanzees and humans. In humans, we found a positive relationship between cerebral aging and cortical expansion, whereas, in chimpanzees no such relationship was found. The greater aging and expansion effects in higher-order cognitive regions like the orbito-frontal cortex were observed to be unique to humans. This resembles the last in, first out hypothesis for neurodevelopment and may represent a biological cost for recent evolutionary developments of human faculties.

neuroscience↗

CAT - A Computational Anatomy Toolbox for the Analysis of Structural MRI Data

A large range of sophisticated brain image analysis tools have been developed by the neuroscience community, greatly advancing the field of human brain mapping. Here we introduce the Computational Anatomy Toolbox (CAT) - a powerful suite of tools for brain morphometric analyses with an intuitive graphical user interface, but also usable as a shell script. CAT is suitable for beginners, casual users, experts, and developers alike providing a comprehensive set of analysis options, workflows, and integrated pipelines. The available analysis streams - illustrated on an example dataset - allow for voxel-based, surface-based, as well as region-based morphometric analyses. Notably, CAT incorporates multiple quality control options and covers the entire analysis workflow, including the preprocessing of cross-sectional and longitudinal data, statistical analysis, and the visualization of results. The overarching aim of this article is to provide a complete description and evaluation of CAT, while offering a citable standard for the neuroscience community.

neuroscience↗

To smooth or not to smooth: One step closer to single-voxel accuracy without spatial smoothing

Traditionally, when conducting voxel- or vertex-wise analyses in neuroimaging studies, it seemed imperative that brain data are convoluted with a Gaussian kernel, a procedure known as "spatial smoothing". However, we suggest that - under certain conditions - smoothing may be omitted for the benefit of an improved regional specificity. We demonstrate the suitability of this omission by combining high-dimensional spatial registration and threshold-free cluster enhancement (TFCE) in a sample of 754 brains. Our findings revealed that, without smoothing, it is possible to capture brain atrophy within the hippocampal complex while dissociating neighboring areas (cornu ammonis, dentate gyrys, subiculum, and amygdala). In contrast, the traditional smoothing step would result in a single hippocampal cluster (the larger the smoothing kernel, the lower the specificity). Supplemental analyses not only varying the size of the smoothing kernel, but also the size of the sample, the signal-to-noise ratio, as well as the accuracy of the spatial registration confirm that no smoothing (or less smoothing) leads to increased specificity while maintaining sensitivity, at least for small-scale structures (e.g., hippocampus and amygdala). Nevertheless, classic analyses based on smoothed data will continue to provide important insights, especially for large-scale structures (e.g., cortical regions).

neuroscience↗

Chimpanzee Brain Morphometry Utilizing Standardized MRI Preprocessing and Macroanatomical Annotations

Chimpanzees are among the closest living relatives to humans and, as such, provide a crucial comparative model for investigating primate brain evolution. In recent years, human brain mapping has strongly benefited from enhanced computational models and image processing pipelines that could also improve data analyses in animals by using species-specific templates. In this study, we use structural MRI data from the National Chimpanzee Brain Resource (NCBR) to develop the chimpanzee brain reference template Juna.Chimp for spatial registration and the macro-anatomical brain parcellation Davi130 for standardized whole-brain analysis. Additionally, we introduce a ready-to-use image processing pipeline built upon the CAT12 toolbox in SPM12, implementing a standard human image preprocessing framework in chimpanzees. Applying this approach to data from 178 subjects, we find strong evidence for age-related GM atrophy in multiple regions of the chimpanzee brain, as well as, a human-like anterior-posterior pattern of hemi-spheric asymmetry in medial chimpanzee brain regions.

neuroscience↗