No abstract

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human wholebrain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Functional MRI signals can be heavily influenced by systemic physiological processes in addition to local neural activity. For example, widespread hemodynamic fluctuations across the brain have been found to correlate with natural, low-frequency variations in the depth and rate of breathing over time. Acquiring peripheral measures of respiration during fMRI scanning not only allows for modeling such effects in fMRI analysis, but also provides valuable information for interrogating brain-body physiology. However, physiological recordings are frequently unavailable or have insufficient quality. Here, we propose a computational technique for reconstructing continuous low-frequency respiration volume (RV) fluctuations from fMRI data alone. We evaluate the performance of this approach across different fMRI preprocessing strategies. Further, we demonstrate that the predicted RV signals can account for similar patterns of temporal variation in resting-state fMRI data compared to measured RV fluctuations. These findings indicate that fluctuations in respiration volume can be extracted from fMRI alone, in the common scenario of missing or corrupted respiration recordings. The results have implications for enriching a large volume of existing fMRI datasets through retrospective addition of respiratory variations information.

Diffusion weighted MRI (DWMRI) and the myriad of analysis approaches (from tensors to spherical harmonics and brain tractography to body multi-compartment models) depend on accurate quantification of the apparent diffusion coefficient (ADC). Signal drift during imaging (e.g., due to b0 drift associated with heating) can cause systematic non-linearities that manifest as ADC changes if not corrected. Herein, we present a case study on two phantoms on one scanner. Different scan protocols exhibit different degrees of drift during similar scans and may be sensitive to the order of scans within an exam. Vos et al. recently reviewed the effects of signal drift in DWMRI acquisitions and proposed a temporal model for correction. We propose a novel spatialtemporal model to correct for higher order aspects of the signal drift and derive a statistically robust variant. We evaluate the Vos model and propose a method using two phantoms that mimic the ADC of the relevant brain tissue (0.36-2.2 x 10-3 mm 2 /s) on a single 3T scanner. The phantoms are (1) a spherical isotropic sphere consisting of a single concentration of polyvinylpyrrolidone (PVP) and (2) an ice-water phantom with 13 vials of varying PVP concentrations. To characterize the impact of interspersed minimally weighted volumes ("b0's"), image volumes with b-value equal to 0.1 s/mm 2 are interspersed every 8, 16, 32, 48, and 96 diffusion weighted volumes in different trials. Signal drift is found to have spatially varying effects that are not accounted for with temporal-only models. The novel model captures drift more accurately (i.e., reduces the overall change per-voxel over the course of a scan) and results in more consistent ADC metrics.

Reproducible identification of white matter tracts across subjects is essential for the study of structural connectivity of the human brain. One of the key challenges is anatomical differences between subjects. Labeling white matter regions of interest presents many challenges due to the need to integrate both local and global information. Clearly communicating the human/manual processes to capture this information is cumbersome, and the state-of-the-art for white matter atlas is the population-averaged Johns Hopkins Eve atlas. A critical bottleneck with the Eve atlas framework is that manual labeling time is extensive and peripheral white matter regions are conservatively labeled. In this work, we developed and tested a protocol for a simpler and flexible approach based on modern tractography definitions. The TractEM protocols for whole brain tractography take less than 6 hours for one subject. We tested the protocols on 61 unique tracts for 20 subjects manually labeled at least twice per subject. We analyzed reproducibility of the fiber bundles using volumetric overlap metrics, Dice correlation coefficient, continuous Dice correlation coefficient; distance metric, root mean squared error; and probabilistic intraclass correlation (ICC). Raters with minimal neuroanatomical expertise attained good and high reproducibility for typical 3T research resolution and high-resolution Human Connectome Project datasets, respectively. While the existing tractography methods tend to cover larger tracts and target only a limited number of tracts, the TractEM manual labeling protocols allow for reconstruction of reproducible region-specific fiber bundles across the brain. The protocols and sample results have been made available in open source.