arXiv subjects

Suzanne N. Haber

Publications and source records attributed to Suzanne N. Haber.

7 recordsLinked to original sources

arXiv2026

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↗

arXiv2026

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↗

arXiv2025

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↗

arXiv2025

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↗

arXiv2025

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↗

arXiv2022

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↗

arXiv2009

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.

q-bio.NC↗