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Diffusion MRI and anatomic tracing in the same brain reveal common failure modes of tractography.

ABSTRACT: Anatomic tracing is recognized as a critical source of knowledge on brain circuitry that can be used to assess the accuracy of diffusion MRI (dMRI) tractography. However, most prior studies that have performed such assessments have used dMRI and tracer data from different brains and/or have been limited in the scope of dMRI analysis methods allowed by the data. In this work, we perform a quantitative, voxel-wise comparison of dMRI tractography and anatomic tracing data in the same macaque brain. An ex vivo dMRI acquisition with high angular resolution and high maximum b-value allows us to compare a range of q-space sampling, orientation reconstruction, and tractography strategies. The availability of tracing in the same brain allows us to localize the sources of tractography errors and to identify axonal configurations that lead to such errors consistently, across dMRI acquisition and analysis strategies. We find that these common failure modes involve geometries such as branching or turning, which cannot be modeled well by crossing fibers. We also find that the default thresholds that are commonly used in tractography correspond to rather conservative, low-sensitivity operating points. While deterministic tractography tends to have higher sensitivity than probabilistic tractography in that very conservative threshold regime, the latter outperforms the former as the threshold is relaxed to avoid missing true anatomical connections. On the other hand, the q-space sampling scheme and maximum b-value have less of an impact on accuracy. Finally, using scans from a set of additional macaque brains, we show that there is enough inter-individual variability to warrant caution when dMRI and tracer data come from different animals, as is often the case in the tractography validation literature. Taken together, our results provide insights on the limitations of current tractography methods and on the critical role that anatomic tracing can play in identifying potential avenues for improvement.

SUBMITTER: Grisot G

PROVIDER: S-EPMC8475636 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDiffusion tensor imaging (DTI) has been applied in the lumbar and sacral nerves in vivo, but information about the reproducibility of this method is needed before DTI can be used reliably in clinical practice across centers.PurposeIn this multicenter study the reproducibility of DTI of the lumbosacral nerves in healthy volunteers was investigated.Study typeProspective control series.SubjectsTwenty healthy subjects.Field strength/sequence3T MRI. 3D turbo spin echo, and 3.0 mm isotropic DTI scan.AssessmentThe DTI scan was performed three times (twice in the same session, intrascan reproducibility, and once after an hour, interscan reproducibility). At site 2, 1 week later, the protocol was repeated (interweek reproducibility). Fiber tractography (FT) of the lumbar and sacral nerves (L3-S2) was performed to obtain values for fractional anisotropy, mean, axial, and radial diffusivity.Statistical testsReproducibility was determined using the intraclass correlation coefficient (ICC), and power calculations were performed.ResultsFT was successful and reproducible in all datasets. ICCs for all diffusion parameters were high for intrascan (ranging from 0.70-0.85), intermediate for interscan (ranging from 0.61-0.73), and interweek reliability (ranging from 0.58-0.62). There were small but significant differences between the interweek diffusivity values (P < 0.0005). Depending on the effect size, nerve location, and parameter of interest, power calculations showed that sample sizes between 10 and 232 subjects are needed for cross-sectional studies.Data conclusionWe found that DTI and FT of the lumbosacral nerves have intermediate to high reproducibility within and between scans. Based on these results, 10-58 subjects are needed to find a 10% change in parameters in cross-sectional studies of the lumbar and sacral nerves. The small significant differences of the interweek comparison suggest that results from longitudinal studies need to be interpreted carefully, since small differences may also be caused by factors other than disease progression or therapeutic effects.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:951-963.

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Diffusion MRI and anatomic tracing in the same brain reveal common failure modes of tractography.

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