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Kurt G. Schilling

Publications and source records attributed to Kurt G. Schilling.

At least 19 recordsLinked to original sources

Large-Scale Deployment and Analytical Implications of Structured Quality Control in Diffusion Magnetic Resonance Imaging

Purpose: Diffusion MRI (dMRI) provides a diverse set of quantitative measures and derived datatypes to assess white matter microstructure and macrostructure. Coupled with the increasing size of imaging studies using dMRI, the number of downstream outputs requiring quality control (QC) will continue to grow. Previous work has shown that failure modes which are often not evident from aggregate metrics or summary statistics can be identified through structured visual inspection. This work aims to better understand common failure modes and the expected characteristics of valid dMRI processing outputs to ensure the validity and interpretability of quantitative findings. Approach: We deployed a structured QC framework to assess 18,328 dMRI scans across nine datasets, visually evaluating the outputs of seven processing pipelines representative of conventional dMRI analyses. Results: Downstream outputs that pass visual QC may still rely on failed upstream dependencies; such failures may only be visually detectable through systematic inspection of the full pipeline hierarchy. Additionally, appropriate QC granularity is algorithm-specific, as the spatial structure of each algorithm's outputs determines whether failures warrant selective or global exclusion. Conclusion: This work demonstrates the feasibility and analytical value of large-scale, structured QC for dMRI processing pipelines. Our results highlight the need for systematic QC spanning the full processing hierarchy to ensure the validity and interpretability of quantitative findings.

eess.IV↗

ECLARE: Efficient cross-planar learning for anisotropic resolution enhancement

In clinical imaging, magnetic resonance (MR) image volumes are often acquired as stacks of 2D slices with decreased scan times, improved signal-to-noise ratio, and image contrasts unique to 2D MR pulse sequences. While this is sufficient for clinical evaluation, automated algorithms designed for 3D analysis perform poorly on multi-slice 2D MR volumes, especially those with thick slices and gaps between slices. Super-resolution (SR) methods aim to address this problem, but previous methods do not address all of the following: slice profile shape estimation, slice gap, domain shift, and non-integer or arbitrary upsampling factors. In this paper, we propose ECLARE (Efficient Cross-planar Learning for Anisotropic Resolution Enhancement), a self-SR method that addresses each of these factors. ECLARE uses a slice profile estimated from the multi-slice 2D MR volume, trains a network to learn the mapping from low-resolution to high-resolution in-plane patches from the same volume, and performs SR with anti-aliasing. We compared ECLARE to cubic B-spline interpolation, SMORE, and other contemporary SR methods. We used realistic and representative simulations so that quantitative performance against ground truth can be computed, and ECLARE outperformed all other methods in both signal recovery and downstream tasks. Importantly, as ECLARE does not use external training data it cannot suffer from domain shift between training and testing. Our code is open-source and available at https://www.github.com/sremedios/eclare.

cs.CV↗

Personalized White Matter Bundle Segmentation for Early Childhood

White matter segmentation methods from diffusion magnetic resonance imaging range from streamline clustering-based approaches to bundle mask delineation, but none have proposed a pediatric-specific approach. We hypothesize that a deep learning model with a similar approach to TractSeg will improve similarity between an algorithm-generated mask and an expert-labeled ground truth. Given a cohort of 56 manually labelled white matter bundles, we take inspiration from TractSeg's 2D UNet architecture, and we modify inputs to match bundle definitions as determined by pediatric experts, evaluation to use k fold cross validation, the loss function to masked Dice loss. We evaluate Dice score, volume overlap, and volume overreach of 16 major regions of interest compared to the expert labeled dataset. To test whether our approach offers statistically significant improvements over TractSeg, we compare Dice voxels, volume overlap, and adjacency voxels with a Wilcoxon signed rank test followed by false discovery rate correction. We find statistical significance across all bundles for all metrics with one exception in volume overlap. After we run TractSeg and our model, we combine their output masks into a 60 label atlas to evaluate if TractSeg and our model combined can generate a robust, individualized atlas, and observe smoothed, continuous masks in cases that TractSeg did not produce an anatomically plausible output. With the improvement of white matter pathway segmentation masks, we can further understand neurodevelopment on a population level scale, and we can produce reliable estimates of individualized anatomy in pediatric white matter diseases and disorders.

eess.IV↗

Fully Differentiable dMRI Streamline Propagation in PyTorch

Diffusion MRI (dMRI) provides a distinctive means to probe the microstructural architecture of living tissue, facilitating applications such as brain connectivity analysis, modeling across multiple conditions, and the estimation of macrostructural features. Tractography, which emerged in the final years of the 20th century and accelerated in the early 21st century, is a technique for visualizing white matter pathways in the brain using dMRI. Most diffusion tractography methods rely on procedural streamline propagators or global energy minimization methods. Although recent advancements in deep learning have enabled tasks that were previously challenging, existing tractography approaches are often non-differentiable, limiting their integration in end-to-end learning frameworks. While progress has been made in representing streamlines in differentiable frameworks, no existing method offers fully differentiable propagation. In this work, we propose a fully differentiable solution that retains numerical fidelity with a leading streamline algorithm. The key is that our PyTorch-engineered streamline propagator has no components that block gradient flow, making it fully differentiable. We show that our method matches standard propagators while remaining differentiable. By translating streamline propagation into a differentiable PyTorch framework, we enable deeper integration of tractography into deep learning workflows, laying the foundation for a new category of macrostructural reasoning that is not only computationally robust but also scientifically rigorous.

eess.IV↗

Millennium Pathways for Tractography: 40 grand challenges to shape the future of tractography

In the spirit of the historic Millennium Prize Problems that heralded a new era for mathematics, the newly formed International Society for Tractography (IST) has launched the Millennium Pathways for Tractography, a community-driven roadmap designed to shape the future of the field. Conceived during the inaugural Tract-Anat Retreat, this initiative reflects a collective vision for advancing tractography over the coming decade and beyond. The roadmap consists of 40 grand challenges, developed by international experts and organized into seven categories spanning three overarching themes: neuroanatomy, tractography methods, and clinical applications. By defining shared short-, medium-, and long-term goals, these pathways provide a structured framework to confront fundamental limitations, promote rigorous validation, and accelerate the translation of tractography into a robust tool for neuroscience and medicine. Ultimately, the Millennium Pathways aim to guide and inspire future research and collaboration, ensuring the continued scientific and clinical relevance of tractography well into the future.

physics.med-ph↗

Brain age identification from diffusion MRI synergistically predicts neurodegenerative disease

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI) presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that mitigates the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information mitigated, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two recent, popular, openly available T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Furthermore, dMRI-based brain age may offer advantages over T1w MRI-based brain age in predicting the transition from CN to MCI up to five years before diagnosis.

cs.CV↗

Multi-Modality Conditioned Variational U-Net for Field-of-View Extension in Brain Diffusion MRI

An incomplete field-of-view (FOV) in diffusion magnetic resonance imaging (dMRI) can severely hinder the volumetric and bundle analyses of whole-brain white matter connectivity. Although existing works have investigated imputing the missing regions using deep generative models, it remains unclear how to specifically utilize additional information from paired multi-modality data and whether this can enhance the imputation quality and be useful for downstream tractography. To fill this gap, we propose a novel framework for imputing dMRI scans in the incomplete part of the FOV by integrating the learned diffusion features in the acquired part of the FOV to the complete brain anatomical structure. We hypothesize that by this design the proposed framework can enhance the imputation performance of the dMRI scans and therefore be useful for repairing whole-brain tractography in corrupted dMRI scans with incomplete FOV. We tested our framework on two cohorts from different sites with a total of 96 subjects and compared it with a baseline imputation method that treats the information from T1w and dMRI scans equally. The proposed framework achieved significant improvements in imputation performance, as demonstrated by angular correlation coefficient (p < 1E-5), and in downstream tractography accuracy, as demonstrated by Dice score (p < 0.01). Results suggest that the proposed framework improved imputation performance in dMRI scans by specifically utilizing additional information from paired multi-modality data, compared with the baseline method. The imputation achieved by the proposed framework enhances whole brain tractography, and therefore reduces the uncertainty when analyzing bundles associated with neurodegenerative.

cs.CV↗

Robust Containerization of the High Angular Resolution Functional Imaging (HARFI) Pipeline

Historically, functional magnetic resonance imaging (fMRI) of the brain has focused primarily on gray matter, particularly the cortical gray matter and associated nuclei. However, recent work has demonstrated that functional activity in white matter also plays a meaningful role in both cognition and learning. In previous work, we introduced the High Angular Resolution Functional Imaging (HARFI) pipeline, which demonstrated both local and global patterns of functional correlation in white matter. Notably, HARFI enabled exploration of asymmetric voxel-wise correlation using odd-order spherical harmonics. Although the original implementation of HARFI was released via GitHub, adoption was limited due to the technical complexity of running the source code. In this work, we present a robust and efficient containerized version of the HARFI pipeline, enabling seamless execution across multiple public datasets. Our goal is to facilitate broader and deeper exploration of functional white matter architecture, especially through the lens of high angular resolution functional correlations. The key innovation of this work is the containerized implementation, which we have made available under a permissive open-source license to support reproducible and accessible research practices.

physics.med-ph↗

Comparison and calibration of MP2RAGE quantitative T1 values to multi-TI inversion recovery T1 values

While typical qualitative T1-weighted magnetic resonance images reflect scanner and protocol differences, quantitative T1 mapping aims to measure T1 independent of these effects. Changes in T1 in the brain reflect structural changes in brain tissue. Magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) is an acquisition protocol that allows for efficient T1 mapping with a much lower scan time per slab compared to multi-TI inversion recovery (IR) protocols. We collect and register B1-corrected MP2RAGE acquisitions with an additional inversion time (MP3RAGE) alongside multi-TI selective inversion recovery acquisitions for four subjects. We use a maximum a posteriori (MAP) T1 estimation method for both MP2RAGE and compare to typical point estimate MP2RAGE T1 mapping, finding no bias from MAP MP2RAGE but a sensitivity to B1 inhomogeneities with MAP MP3RAGE. We demonstrate a tissue-dependent bias between MAP MP2RAGE T1 estimates and the multi-TI inversion recovery T1 values. To correct this bias, we train a patch-based ResNet-18 to calibrate the MAP MP2RAGE T1 estimates to the multi-TI IR T1 values. Across four folds, our network reduces the RMSE significantly (white matter: from 0.30 +/- 0.01 seconds to 0.11 +/- 0.02 seconds, subcortical gray matter: from 0.26 +/- 0.02 seconds to 0.10 +/- 0.02 seconds, cortical gray matter: from 0.36 +/- 0.02 seconds to 0.17 +/- 0.03 seconds). Using limited paired training data from both sequences, we can reduce the error between quantitative imaging methods and calibrate to one of the protocols with a neural network.

eess.IV↗

Sensitivity of quantitative diffusion MRI tractography and microstructure to anisotropic spatial sampling

Purpose: Diffusion weighted MRI (dMRI) and its models of neural structure provide insight into human brain organization and variations in white matter. A recent study by McMaster, et al. showed that complex graph measures of the connectome, the graphical representation of a tractogram, vary with spatial sampling changes, but biases introduced by anisotropic voxels in the process have not been well characterized. This study uses microstructural measures (fractional anisotropy and mean diffusivity) and white matter bundle properties (bundle volume, length, and surface area) to further understand the effect of anisotropic voxels on microstructure and tractography. Methods: The statistical significance of the selected measures derived from dMRI data were assessed by comparing three white matter bundles at different spatial resolutions with 44 subjects from the Human Connectome Project Young Adult dataset scan/rescan data using the Wilcoxon Signed Rank test. The original isotropic resolution (1.25 mm isotropic) was explored with six anisotropic resolutions with 0.25 mm incremental steps in the z dimension. Then, all generated resolutions were upsampled to 1.25 mm isotropic and 1 mm isotropic. Results: There were statistically significant differences between at least one microstructural and one bundle measure at every resolution (p less than or equal to 0.05, corrected for multiple comparisons). Cohen's d coefficient evaluated the effect size of anisotropic voxels on microstructure and tractography. Conclusion: Fractional anisotropy and mean diffusivity cannot be recovered with basic up sampling from low quality data with gold standard data. However, the bundle measures from tractogram become more repeatable when voxels are resampled to 1 mm isotropic.

eess.SP↗

Scalable quality control on processing of large diffusion-weighted and structural magnetic resonance imaging datasets

Proper quality control (QC) is time consuming when working with large-scale medical imaging datasets, yet necessary, as poor-quality data can lead to erroneous conclusions or poorly trained machine learning models. Most efforts to reduce data QC time rely on outlier detection, which cannot capture every instance of algorithm failure. Thus, there is a need to visually inspect every output of data processing pipelines in a scalable manner. We design a QC pipeline that allows for low time cost and effort across a team setting for a large database of diffusion weighted and structural magnetic resonance images. Our proposed method satisfies the following design criteria: 1.) a consistent way to perform and manage quality control across a team of researchers, 2.) quick visualization of preprocessed data that minimizes the effort and time spent on the QC process without compromising the condition or caliber of the QC, and 3.) a way to aggregate QC results across pipelines and datasets that can be easily shared. In addition to meeting these design criteria, we also provide information on what a successful output should be and common occurrences of algorithm failures for various processing pipelines. Our method reduces the time spent on QC by a factor of over 20 when compared to naively opening outputs in an image viewer and demonstrate how it can facilitate aggregation and sharing of QC results within a team. While researchers must spend time on robust visual QC of data, there are mechanisms by which the process can be streamlined and efficient.

cs.DC↗

Scalable, reproducible, and cost-effective processing of large-scale medical imaging datasets

Curating, processing, and combining large-scale medical imaging datasets from national studies is a non-trivial task due to the intense computation and data throughput required, variability of acquired data, and associated financial overhead. Existing platforms or tools for large-scale data curation, processing, and storage have difficulty achieving a viable cost-to-scale ratio of computation speed for research purposes, either being too slow or too expensive. Additionally, management and consistency of processing large data in a team-driven manner is a non-trivial task. We design a BIDS-compliant method for an efficient and robust data processing pipeline of large-scale diffusion-weighted and T1-weighted MRI data compatible with low-cost, high-efficiency computing systems. Our method accomplishes automated querying of data available for processing and process running in a consistent and reproducible manner that has long-term stability, while using heterogenous low-cost computational resources and storage systems for efficient processing and data transfer. We demonstrate how our organizational structure permits efficiency in a semi-automated data processing pipeline and show how our method is comparable in processing time to cloud-based computation while being almost 20 times more cost-effective. Our design allows for fast data throughput speeds and low latency to reduce the time for data transfer between storage servers and computation servers, achieving an average of 0.60 Gb/s compared to 0.33 Gb/s for using cloud-based processing methods. The design of our workflow engine permits quick process running while maintaining flexibility to adapt to newly acquired data.

cs.DC↗

Harmonized connectome resampling for variance in voxel sizes

To date, there has been no comprehensive study characterizing the effect of diffusion-weighted magnetic resonance imaging voxel resolution on the resulting connectome for high resolution subject data. Similarity in results improved with higher resolution, even after initial down-sampling. To ensure robust tractography and connectomes, resample data to 1 mm isotropic resolution.

physics.med-ph↗

Tractography with T1-weighted MRI and associated anatomical constraints on clinical quality diffusion MRI

Diffusion MRI (dMRI) streamline tractography, the gold standard for in vivo estimation of brain white matter (WM) pathways, has long been considered indicative of macroscopic relationships with WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn and propagate streamlines directly from T1 and anatomical contexts. Training for this network has previously relied on high-resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical protocols. Then, we define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. Under this metric, T1 tractography generated by CoRNN reproduces diffusion tractography with approximately two millimeters of error.

eess.IV↗

Evaluation of Mean Shift, ComBat, and CycleGAN for Harmonizing Brain Connectivity Matrices Across Sites

Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.

q-bio.NC↗

Predicting Age from White Matter Diffusivity with Residual Learning

Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural MRI data has become an important task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest. The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 years for cognitively normal participants and MAE of 6.62 years for cognitively impaired participants, while the second method achieves MAE of 4.69 years for cognitively normal participants and MAE of 4.96 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.

eess.IV↗

Joint analysis of structural connectivity and cortical surface features: correlates with mild traumatic brain injury

Mild traumatic brain injury (mTBI) is a complex syndrome that affects up to 600 per 100,000 individuals, with a particular concentration among military personnel. About half of all mTBI patients experience a diverse array of chronic symptoms which persist long after the acute injury. Hence, there is an urgent need for better understanding of the white matter and gray matter pathologies associated with mTBI to map which specific brain systems are impacted and identify courses of intervention. Previous works have linked mTBI to disruptions in white matter pathways and cortical surface abnormalities. Herein, we examine these hypothesized links in an exploratory study of joint structural connectivity and cortical surface changes associated with mTBI and its chronic symptoms. Briefly, we consider a cohort of 12 mTBI and 26 control subjects. A set of 588 cortical surface metrics and 4,753 structural connectivity metrics were extracted from cortical surface regions and diffusion weighted magnetic resonance imaging in each subject. Principal component analysis (PCA) was used to reduce the dimensionality of each metric set. We then applied independent component analysis (ICA) both to each PCA space individually and together in a joint ICA approach. We identified a stable independent component across the connectivity-only and joint ICAs which presented significant group differences in subject loadings (p<0.05, corrected). Additionally, we found that two mTBI symptoms, slowed thinking and forgetfulness, were significantly correlated (p<0.05, corrected) with mTBI subject loadings in a surface-only ICA. These surface-only loadings captured an increase in bilateral cortical thickness.

q-bio.NC↗

MRI correlates of chronic symptoms in mild traumatic brain injury

Veterans with mild traumatic brain injury (mTBI) have reported auditory and visual dysfunction that persists beyond the acute incident. The etiology behind these symptoms is difficult to characterize with current clinical imaging. These functional deficits may be caused by shear injury or micro-bleeds, which can be detected with special imaging modalities. We explore these hypotheses in a pilot study of multi-parametric MRI. We extract over 1,000 imaging and clinical metrics and project them to a low-dimensional space, where we can discriminate between healthy controls and patients with mTBI. We also show correlations between the metric representations and patient symptoms.

eess.IV↗