Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited
Open accessAbstract
Significance: Diffusion-weighted MRI (DWI) tractography is widely used to map structural connections of the human brain in vivo and has been adopted by large-scale initiatives such as the human connectome project. Our results indicate that, even with high-quality data, DWI tractography alone is unlikely to provide an anatomically accurate map of the brain connectome. It is crucial to complement tractography results with a combination of histological or neurophysiological methods to map structural connectivity accurately. Our findings, however, do not diminish the importance of diffusion MRI as a noninvasive tool that offers important quantitative measures related to brain tissue microstructure and white matter architecture.
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Previous reports found termination of tracts in the gray matter to be inaccurate.
“This finding is in line with previous reports, which found termination of tracts in the gray matter (GM) to be inaccurate5”
From Tractography-based connectomes are dominated by false-positive connections (2016) · cites this paper as [5]
The Discussion reports that DWI tractography had suboptimal anatomical accuracy, including false-positive connections, and Fig. 1 describes comparisons in gray- and white-matter regions. The paper does not specifically establish that tract endpoints terminate inaccurately in gray matter; it assesses agreement between tractography and tracer-labeled regions more broadly. The indexed passages provide section labels but no page numbers. (LLM, conf=0.83)
Experimental — accuracy not yet measuredTractography techniques suffer from a large number of false positive streamlines that do not correspond to real anatomical bundles.
“In particular, it has been shown that tractography techniques suffer from a large number of false positives, i.e., streamlines that are reconstructed but do not correspond to real anatomical bundles”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Thomas et al., 2014
The Discussion (page unavailable) reports that high-sensitivity tractography tends to have a high false-positive rate, supporting the concern about reconstructed pathways without anatomical support. But the paper evaluates false positives by anatomical region, not by counting individual streamlines, and says some methods and settings can achieve much lower false-positive rates. The claim overgeneralizes those findings to tractography techniques as a whole. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe considerable amount of false positive and false negative connections generated by diffusion-based tractography in rat brain is in line with related studies in macaque brain, mouse brain, and human connectome.
“The considerable amount of false positive and false negative connections generated by diffusion-based tractography in rat brain is in line with related studies in macaque brain (Thomas et al. 2014; Azadbakht et al. 2015; Donahue et al. 2016), and mouse brain (Calabrese et al. 2015; Chen et al. 2015), and similar findings have been reported for the human connectome (Maier-Hein et al. 2016).”
From Diffusion MRI-based cortical connectome reconstruction: dependency on tractography procedures and neuroanatomical characteristics (2018) · cites this paper as Thomas et al. 2014
The overall results confirm previously reported trade-offs between sensitivity and specificity of tract reconstructions across tractography methods.
“As such, our overall results confirm previously reported trade-offs between sensitivity and specificity of tract reconstructions across tractography methods (Bastiani et al. 2012; Thomas et al. 2014; Chen et al. 2015; Donahue et al. 2016).”
From Diffusion MRI-based cortical connectome reconstruction: dependency on tractography procedures and neuroanatomical characteristics (2018) · cites this paper as Thomas et al. 2014
The angle threshold might still have affected specific pathway reconstructions in the brain.
“However, the angle threshold might still have affected specific pathway reconstructions in the brain (Thomas et al. 2014).”
From Diffusion MRI-based cortical connectome reconstruction: dependency on tractography procedures and neuroanatomical characteristics (2018) · cites this paper as Thomas et al. 2014
The anatomical accuracy of tractography remains an ongoing issue in quantitative tractography analysis, with both false-positive and false-negative tractography results posing challenges.
“The anatomical accuracy of tractography is an ongoing issue in quantitative tractography analysis, where both false positive and false negative tractography results pose challenges (Maier-Hein et al., 2017; Thomas et al., 2014).”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Thomas et al., 2014
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- Authors
- Thomas, C., Ye, F. Q., Irfanoglu, M. O., Modi, P., Saleem, K. S., Leopold, D. A., & Pierpaoli, C.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- National Institute of Neurological Disorders and Stroke (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- National Institutes of Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-11-03
- Volume
- 111
- Issue
- 46
- Pages
- 16574-16579
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4246325
- OpenAlex
- W2091910928
- Cited by
- 725
- References
- 64
- Citations by year
- 2026: 34 · 2025: 59 · 2024: 45 · 2023: 34 · 2022: 50 · 2021: 76 · 2020: 69 · 2019: 73 · 2018: 84 · 2017: 80 · 2016: 65 · 2015: 55
- FWCI
- 52.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- Center for Neuroscience and Regenerative Medicine
- National Institute of Mental Health
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- diffusion MRI tractography, anatomical accuracy, macaque brain, axonal projections, ex vivo brain, tracer studies, sensitivity and specificity, fiber orientation estimation
- MeSH terms
- Algorithms, Animals, Axons, Axonal Transport, Body Water, Contrast Media, Diffusion, Leucine, Macaca mulatta, Male, Models, Neurological, Motor Cortex, Occipital Lobe, Proline, Research Design, ROC Curve, Sensitivity and Specificity, Tritium, Gadolinium DTPA, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Connectome, White Matter
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