Searcharxiv⌕ Search

arXiv subjects

Anastasia Yendiki

Publications and source records attributed to Anastasia Yendiki.

11 recordsLinked to original sources

AxonSynth: Domain-Randomized Synthetic Data for Zero-Shot 3D Axon Segmentation in Light-Sheet Microscopy

Accurate segmentation of axons in 3D microscopy data is important for analyzing white-matter organization, but dense ground truth labels are expensive to obtain. Existing supervised axon segmentation methods rely on target-domain annotations and can be brittle when tissue type, species, modality, or acquisition conditions change. We present AxonSynth, a domain-randomized synthetic-data framework for training 3D axon segmentation models without manually annotated real training volumes. AxonSynth generates dense synthetic axon labels with orientation priors that reflect realistic fiber configurations and renders them with randomized density, contrast, bias fields, blur, and noise. A three-class 3D U-Net is trained to predict background, axon sheath and intra-axonal space. We evaluate zero-shot transfer on 10 held-out light-sheet microscopy (LSM) patches from macaque and human brain samples labeled with one of three axonal markers, comparing against calibrated thresholding and Frangi filtering using overlap, corrected detection, false-positive, and topology metrics. On macaque samples, AxonSynth achieved the best corrected Dice and corrected precision (0.826 and 0.851), compared with 0.765 and 0.754 for thresholding and 0.685 and 0.762 for Frangi. On human samples, corrected Dice was comparable to thresholding (0.857 vs. 0.868), while component-count error decreased from 22,504 to 3,377. Across all held-out patches, AxonSynth reduced component-count error in 10/10 patches and Euler-characteristic error in 8/10. These results show that synthetic-label domain randomization can reduce dependence on manual axon annotation while supporting synthetic-to-real 3D segmentation.

cs.CV↗

Topology-Aware Training and Spatial Diagnostics for Fiber Bundle Segmentation in Tracer Histology

Anatomic tracer studies reveal how axon bundles project from an injection site, branch into smaller groups of axons, and course through the brain to reach their destinations. Histological data from such studies provide anatomical reference information for validating diffusion MRI tractography. However, manual annotation of the histological data is very labor-intensive, and although automated segmentation methods have been proposed, they rely mainly on pixel-overlap losses such as BCE and Dice; topology-aware loss functions have not been studied for this task. We compare BCE-Dice, clDice, Betti matching, and Topograph for fiber bundle segmentation in macaque tracer histology using a frozen DINOv3 backbone. To our knowledge, this is the first exploration of foundation-model features for this task. BCE-Dice achieved the highest Dice, while clDice achieved the highest bundle recall but poor mask overlap. Topograph had similar Dice to BCE-Dice, the lowest $β_0$ error, and fewer false positives than BCE-Dice and Betti matching. Fiber bundle segmentation methods are typically evaluated with a permissive rule that counts a bundle as detected given any overlap with the prediction. We show this rule does not capture oversegmentation, and that per-section TPR can be inflated by empty sections assigned perfect recall. To quantify this, we introduce Excess32, a spatial diagnostic measuring predicted pixels outside a 32-pixel tolerance band around annotated bundles. In validation, a Betti-Topograph union raises sparse-bundle TPR from 0.818 to 0.933, but worsens FDR from 0.296 to 0.509, Excess32 from 0.108 to 0.466, and area ratio from 0.94 to 3.34. These results show detection metrics alone are insufficient to characterize segmentation quality.

cs.CV↗

Tractography-Driven Synthetic Data Generation for Fiber Bundle Segmentation in Tracer Histology

Diffusion MRI (dMRI) tractography enables non-invasive reconstruction of white-matter pathways, but its accuracy is fundamentally limited by indirect, low-resolution measurements of axonal organization. Tracer injection studies in non-human primates provide a gold standard for validating dMRI tractography. This, however, requires time-consuming manual annotation of fiber bundles in histology sections. We propose a synthetic-data augmented framework for automated fiber bundle segmentation in macaque tracer histology. Our approach uses ex vivo dMRI tractography as a generative prior to synthesize 2D image patches for training. This provides us with sufficiently realistic foreground texture, which we compose with backgrounds from blockface photos and diversify via domain randomization. A 2D U-Net is trained on mixed real and synthetic patches. Experiments on held-out brains demonstrate improved generalization across brains and fiber bundle densities compared to training with real data only. Training with synthetic data only leads to poor performance, underscoring the need for real supervision. Overall, our approach achieves performance comparable to the state-of-the-art while requiring 3x less manually annotated data.

cs.CV↗

Fully Automated Segmentation of Fiber Bundles in Anatomic Tracing Data

Anatomic tracer studies are critical for validating and improving diffusion MRI (dMRI) tractography. However, large-scale analysis of data from such studies is hampered by the labor-intensive process of annotating fiber bundles manually on histological slides. Existing automated methods often miss sparse bundles or require complex post-processing across consecutive sections, limiting their flexibility and generalizability. We present a streamlined, fully automated framework for fiber bundle segmentation in macaque tracer data, based on a U-Net architecture with large patch sizes, foreground aware sampling, and semisupervised pre-training. Our approach eliminates common errors such as mislabeling terminals as bundles, improves detection of sparse bundles by over 20% and reduces the False Discovery Rate (FDR) by 40% compared to the state-of-the-art, all while enabling analysis of standalone slices. This new framework will facilitate the automated analysis of anatomic tracing data at a large scale, generating more ground-truth data that can be used to validate and optimize dMRI tractography methods.

cs.CV↗

PRIME: Phase Reversed Interleaved Multi-Echo acquisition enables highly accelerated distortion-free diffusion MRI

Purpose: To develop and evaluate a new pulse sequence for highly accelerated distortion-free diffusion MRI (dMRI) by inserting additional echoes without prolonging TR, when generalized slice dithered enhanced resolution (gSlider) radiofrequency encoding is used for volumetric acquisition. Methods: A phase-reversed interleaved multi-echo acquisition (PRIME) was developed for rapid, high-resolution, and distortion-free dMRI, which includes several echoes where the first echo is for target diffusion-weighted imaging (DWI) acquisition with high-resolution and additional echoes are acquired with either lower resolution for 1) high-fidelity field map estimation, 2) phase navigation for shot-to-shot phase correction, 3) motion navigation across diffusion directions, or with high resolution to enable 4) high fidelity diffusion relaxometry acquisitions. The sequence was evaluated on in vivo data acquired from healthy volunteers on clinical and Connectome 2.0 scanners. Results: In vivo experiments demonstrated that 1) high in-plane acceleration (Rin-plane of 5-fold with 2D partial Fourier) was achieved using the high-fidelity field maps estimated from the second echo, which was made at a lower resolution/acceleration to increase its SNR while matching the effective echo spacing of the first readout, 2) high-resolution diffusion relaxometry parameters were estimated from triple-echo PRIME data using a white matter model of multi-TE spherical mean technique (MTE-SMT), and 3) high-fidelity mesoscale DWI at 490 um isotropic resolution was obtained in vivo by capitalizing on the high-performance gradients of the Connectome 2.0 scanner. Conclusion: The proposed PRIME sequence enabled highly accelerated, high-resolution, and distortion-free dMRI using additional echoes without prolonging scan time when gSlider encoding is utilized.

physics.med-ph↗

Interplay between MRI-based axon diameter and myelination estimates in macaque and human brain

Axon diameter and myelin thickness affect the conduction velocity of action potentials in the nervous system. Imaging them non-invasively with MRI-based methods is thus valuable for studying brain microstructure and function. Electron microscopy studies suggest that axon diameter and myelin thickness are closely related to each other. However, the relationship between MRI-based estimates of these microstructural measures, known to be relative indices, have not been investigated across the brain mainly due to methodological limitations. In recent years, studies using ultra-high gradient strength diffusion MRI (dMRI) have demonstrated improved estimation of axon diameter index across white-matter (WM) tracts in the human brain, making such investigations feasible. In this study, we aim to investigate relationships between tissue microstructure properties across white-matter tracts, as estimated with MRI-based methods. We collected dMRI with ultra-high gradient strength and multi-echo spin-echo MRI on ex vivo macaque and human brain samples on a preclinical scanner. From these data, we found that the correlations between axon diameter index and other microstructural imaging parameters were weak but consistent across WM tracts in samples estimated with sufficient signal to noise ratio. In well-myelinated regions, tissue voxels with larger axon diameter indices were associated with lower packing density, lower MWF and a tendency of higher g-ratio. We also found that intra-axonal signal fractions and MWF were not consistently correlated when assessed in different samples. Overall, the findings suggest that MRI-based axon geometry and myelination measures can provide complementary information about fiber morphology, and the relationships between these measures agree with prior electron microscopy studies in smaller field of views.

physics.med-ph↗

Microstructure.jl: a Julia Package for Probabilistic Microstructure Model Fitting with Diffusion MRI

Microstructure.jl is a Julia package designed for probabilistic estimation of tissue microstructural parameters from diffusion or combined diffusion-relaxometry MRI data. It provides a flexible and extensible framework for defining compartment models and includes robust and unified estimators for parameter fitting and uncertainty quantification. The package incorporates several established models from the literature, such as the spherical mean technique and soma and neurite density imaging (SANDI), along with their extensions for analyzing combined diffusion and T2 mapping data acquired at multiple echo times. For parameter estimation, it features methods like Markov Chain Monte Carlo (MCMC) sampling and Monte Carlo dropout with neural networks, which provide probabilistic estimates by approximating the posterior distributions of model parameters. In this study, we introduce the major modules, functionality, and design of this package. We demonstrate its usage in optimizing acquisition protocols and evaluating model fitting performance with synthesized datasets. We also showcase practical applications with publicly available datasets. Microstructure.jl is applicable to in vivo and ex vivo imaging data acquired with typical research, high-performance, or pre-clinical scanners.

physics.med-ph↗

Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.

eess.IV↗

Constrained self-supervised method with temporal ensembling for fiber bundle detection on anatomic tracing data

Anatomic tracing data provides detailed information on brain circuitry essential for addressing some of the common errors in diffusion MRI tractography. However, automated detection of fiber bundles on tracing data is challenging due to sectioning distortions, presence of noise and artifacts and intensity/contrast variations. In this work, we propose a deep learning method with a self-supervised loss function that takes anatomy-based constraints into account for accurate segmentation of fiber bundles on the tracer sections from macaque brains. Also, given the limited availability of manual labels, we use a semi-supervised training technique for efficiently using unlabeled data to improve the performance, and location constraints for further reduction of false positives. Evaluation of our method on unseen sections from a different macaque yields promising results with a true positive rate of ~0.90. The code for our method is available at https://github.com/v-sundaresan/fiberbundle_seg_tracing.

eess.IV↗

Learning Anatomical Segmentations for Tractography from Diffusion MRI

Deep learning approaches for diffusion MRI have so far focused primarily on voxel-based segmentation of lesions or white-matter fiber tracts. A drawback of representing tracts as volumetric labels, rather than sets of streamlines, is that it precludes point-wise analyses of microstructural or geometric features along a tract. Traditional tractography pipelines, which do allow such analyses, can benefit from detailed whole-brain segmentations to guide tract reconstruction. Here, we introduce fast, deep learning-based segmentation of 170 anatomical regions directly on diffusion-weighted MR images, removing the dependency of conventional segmentation methods on T 1-weighted images and slow pre-processing pipelines. Working natively in diffusion space avoids non-linear distortions and registration errors across modalities, as well as interpolation artifacts. We demonstrate consistent segmentation results between 0 .70 and 0 .87 Dice depending on the tissue type. We investigate various combinations of diffusion-derived inputs and show generalization across different numbers of gradient directions. Finally, integrating our approach to provide anatomical priors for tractography pipelines, such as TRACULA, removes hours of pre-processing time and permits processing even in the absence of high-quality T 1-weighted scans, without degrading the quality of the resulting tract estimates.

eess.IV↗

Joint inference on structural and diffusion MRI for sequence-adaptive Bayesian segmentation of thalamic nuclei with probabilistic atlases

Segmentation of structural and diffusion MRI (sMRI/dMRI) is usually performed independently in neuroimaging pipelines. However, some brain structures (e.g., globus pallidus, thalamus and its nuclei) can be extracted more accurately by fusing the two modalities. Following the framework of Bayesian segmentation with probabilistic atlases and unsupervised appearance modeling, we present here a novel algorithm to jointly segment multi-modal sMRI/dMRI data. We propose a hierarchical likelihood term for the dMRI defined on the unit ball, which combines the Beta and Dimroth-Scheidegger-Watson distributions to model the data at each voxel. This term is integrated with a mixture of Gaussians for the sMRI data, such that the resulting joint unsupervised likelihood enables the analysis of multi-modal scans acquired with any type of MRI contrast, b-values, or number of directions, which enables wide applicability. We also propose an inference algorithm to estimate the maximum-a-posteriori model parameters from input images, and to compute the most likely segmentation. Using a recently published atlas derived from histology, we apply our method to thalamic nuclei segmentation on two datasets: HCP (state of the art) and ADNI (legacy) - producing lower sample sizes than Bayesian segmentation with sMRI alone.

cs.CV↗