Tractography Pipeline Research Articles

Asymmetry of the Frontal Aslant Tract Depends on Handedness.

The human brain displays structural and functional disparities between its hemispheres, with such asymmetry extending to the frontal aslant tract. This plays a role in a variety of cognitive functions, including speech production, language processing, and executive functions. However, the factors influencing the laterality of the frontal aslant tract remain incompletely understood. Handedness is hypothesized to impact frontal aslant tract laterality, given its involvement in both language and motor control. In this study, we aimed to investigate the relationship between handedness and frontal aslant tract lateralization, providing insight into this aspect of brain organization. The Automated Tractography Pipeline was used to generate the frontal aslant tract for both right and left hemispheres in a cohort of 720 subjects sourced from the publicly available Human Connectome Project in Aging database. Subsequently, macrostructural and microstructural parameters of the right and left frontal aslant tract were extracted for each individual in the study population. The Edinburgh Handedness Inventory scores were used for the classification of handedness, and a comparative analysis across various handedness groups was performed. An age-related decline in both macrostructural parameters and microstructural integrity was noted within the studied population. The frontal aslant tract demonstrated a greater volume and larger diameter in male subjects compared with female participants. Additionally, a left-side laterality of the frontal aslant tract was observed within the general population. In the right-handed group, the volume (P < .001), length (P < .001), and diameter (P = .004) of the left frontal aslant tract were found to be higher than those of the right frontal aslant tract. Conversely, in the left-handed group, the volume (P = .040) and diameter (P = .032) of the left frontal aslant tract were lower than those of the right frontal aslant tract. Furthermore, in the right-handed group, the volume and diameter of the frontal aslant tract showed left-sided lateralization, while in the left-handed group, a right-sided lateralization was evident. The laterality of the frontal aslant tract appears to differ with handedness. This finding highlights the complex interaction between brain lateralization and handedness, emphasizing the importance of considering handedness as a factor in evaluating brain structure and function.

A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule

BackgroundThe anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. MethodsFollowing algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. ResultsWe successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. ConclusionsOur diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.

Predictability of intelligence and age from structural connectomes.

In this study, structural images of 1048 healthy subjects from the Human Connectome Project Young Adult study and 94 from ADNI-3 study were processed by an in-house tractography pipeline and analyzed together with pre-processed data of the same subjects from braingraph.org. Whole brain structural connectome features were used to build a simple correlation-based regression machine learning model to predict intelligence and age of healthy subjects. Our results showed that different forms of intelligence as well as age are predictable to a certain degree from diffusion tensor imaging detecting anatomical fiber tracts in the living human brain. Though we did not identify significant differences in the prediction capability for the investigated features depending on the imaging feature extraction method, we did find that crystallized intelligence was consistently better predictable than fluid intelligence from structural connectivity data through all datasets. Our findings suggest a practical and scalable processing and analysis framework to explore broader research topics employing brain MR imaging.

MaPPeRTrac: A Massively Parallel, Portable, and Reproducible Tractography Pipeline.

Large-scale diffusion MRI tractography remains a significant challenge. Users must orchestrate a complex sequence of instructions that requires many software packages with complex dependencies and high computational costs. We developed MaPPeRTrac, an edge-centric tractography pipeline that simplifies and accelerates this process in a wide range of high-performance computing (HPC) environments. It fully automates either probabilistic or deterministic tractography, starting from a subject's magnetic resonance imaging (MRI) data, including structural and diffusion MRI images, to the edge density image (EDI) of their structural connectomes. Dependencies are containerized with Singularity (now called Apptainer) and decoupled from code to enable rapid prototyping and modification. Data derivatives are organized with the Brain Imaging Data Structure (BIDS) to ensure that they are findable, accessible, interoperable, and reusable following FAIR principles. The pipeline takes full advantage of HPC resources using the Parsl parallel programming framework, resulting in the creation of connectome datasets of unprecedented size. MaPPeRTrac is publicly available and tested on commercial and scientific hardware, so it can accelerate brain connectome research for a broader user community. MaPPeRTrac is available at: https://github.com/LLNL/mappertrac .

An individualized tractography pipeline for the nucleus basalis of Meynert lateral tract

Abstract Background: At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in Parkinson’s disease (PD). Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM. Methods: Using structural and diffusion-weighted imaging, we developed a tractography pipeline using manually segmented regions of interest for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual segmentation pipeline is more reliable than an existing automatic segmentation pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients. Results: The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p &amp;lt; 0.001) and the reconstruction of the target lateral tract (p = 0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p = 0.25), which showed high inter- (mean Dice coefficient &amp;gt;0.6) and intra-rater (mean Dice coefficient &amp;gt;0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts. Conclusion: We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical-grade imaging of healthy young adult and PD patient scans.

Model Averaging and Bootstrap Consensus‐based Uncertainty Reduction in Diffusion MRI Tractography

AbstractDiffusion magnetic resonance imaging (dMRI) tractography has the unique ability to reconstruct major white matter tracts non‐invasively and is, therefore, widely used in neurosurgical planning and neuroscience. In this work, we reduce two sources of uncertainty within the tractography pipeline. The first one is the model uncertainty that arises in crossing fibre tractography, from having to estimate the number of relevant fibre compartments in each voxel. We propose a mathematical framework to estimate model uncertainty, and we reduce this type of uncertainty with a model averaging approach that combines the fibre direction estimates from all candidate models, weighted by the posterior probability of the respective model. The second source of uncertainty is measurement noise. We use bootstrapping to estimate this data uncertainty, and consolidate the fibre direction estimates from all bootstraps into a consensus model. We observe that, in most voxels, a traditional model selection strategy selects different models across bootstraps. In this sense, the bootstrap consensus also reduces model uncertainty. Either approach significantly increases the accuracy of crossing fibre tractography in multiple subjects, and combining them provides an additional benefit. However, model averaging is much more efficient computationally.

Automated detection of axonal damage along white matter tracts in acute severe traumatic brain injury

New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI.

New insights into anatomical connectivity along the anterior-posterior axis of the human hippocampus using in vivo quantitative fibre tracking.

The hippocampus supports multiple cognitive functions including episodic memory. Recent work has highlighted functional differences along the anterior-posterior axis of the human hippocampus, but the neuroanatomical underpinnings of these differences remain unclear. We leveraged track-density imaging to systematically examine anatomical connectivity between the cortical mantle and the anterior-posterior axis of the in vivo human hippocampus. We first identified the most highly connected cortical areas and detailed the degree to which they preferentially connect along the anterior-posterior axis of the hippocampus. Then, using a tractography pipeline specifically tailored to measure the location and density of streamline endpoints within the hippocampus, we characterised where these cortical areas preferentially connect within the hippocampus. Our results provide new and detailed insights into how specific regions along the anterior-posterior axis of the hippocampus are associated with different cortical inputs/outputs and provide evidence that both gradients and circumscribed areas of dense extrinsic anatomical connectivity exist within the human hippocampus. These findings inform conceptual debates in the field and emphasise the importance of considering the hippocampus as a heterogeneous structure. Overall, our results represent a major advance in our ability to map the anatomical connectivity of the human hippocampus in vivo and inform our understanding of the neural architecture of hippocampal-dependent memory systems in the human brain.

Full cervical cord tractography: A new method for clinical use.

Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manual filtering or multiple regions of interest seeding that could help neurosurgeons manage various spinal cord disorders. Four healthy volunteers and two patients with either cervical intramedullary tumors or spinal cord injuries were included. Diffusion-weighted images of the cervical spinal cord were acquired using a Philips 3 Tesla machine, 32 diffusion directions, 1,000 s/mm2 b-value, 2 × 2 × 2 mm voxel size, reduced field-of-view (ZOOM), with two opposing phase-encoding directions. Distortion corrections were then achieved using the FSL software package, and tracking of the full cervical spinal cord was performed using the DSI Studio software (quantitative anisotropy-based deterministic algorithm). A unique region of avoidance was used to exclude everything that is not of the nervous system. Fiber tracking parameters used adaptative fractional anisotropy from 0.015 to 0.045, fiber length from 10 to 1,000 mm, and angular threshold of 90°. In all participants, a full cervical cord tractography was performed from the medulla to the C7 spine level. On a ventral view, the junction between the medulla and spinal cord was identified with its pyramidal bulging, and by an invagination corresponding to the median ventral sulcus. On a dorsal view, the fourth ventricle—superior, middle, and inferior cerebellar peduncles—was seen, as well as its floor and the obex; and gracile and cuneate tracts were recognized on each side of the dorsal median sulcus. In the case of the intramedullary tumor or spinal cord injury, the spinal tracts were seen to be displaced, and this helped to adjust the neurosurgical strategy. This new full tractography approach simplifies the tractography pipeline and provides a reliable 3D-rendering of the spinal cord that could help to adjust the neurosurgical strategy.

CTtrack: A CNN+Transformer-based framework for fiber orientation estimation & tractography

In recent years, multiple data-driven fiber orientation distribution function (fODF) estimation algorithms and automatic tractography pipelines have been proposed to address the limitations of traditional methods. However, these approaches lack precision and generalizability. To tackle these shortcomings, we introduce CTtrack, a CNN+Transformer-based pipeline to estimate fODFs and perform tractography. In this approach, a convolutional neural network (CNN) module is employed to project the resampled diffusion-weighted magnetic resonance imaging (DW-MRI) data to a lower dimension. Then, a transformer model estimates the fiber orientation distribution functions using the projected data within a local block around each voxel. The proposed model represents the extracted fODFs by spherical harmonics coefficients. The predicted fiber ODFs can be used for both deterministic and probabilistic tractography. Our pipeline was tested in terms of the precision and robustness in estimating fODFs and performing tractography using both simulated and real diffusion data. The Tractometer tool was employed to compare our method with the classical and data-driven tractography approaches. The qualitative and quantitative assessments illustrate the competitive performance of our framework compared to other available algorithms.

Probabilistic Tractography to Predict the Position of Cranial Nerves Displaced by Skull Base Tumors: Value for Surgical Strategy Through a Case Series of 62 Patients

Predicting the displacement of cranial nerves by tumors could make surgery safer and the outcome better. Recent advances in imaging and processing have overcome some of the limits associated with cranial nerve tractography, such as spatial resolution and fiber crossing. Among others, probabilistic algorithms yield to a more accurate depiction of cranial nerve trajectories. To report how cranial nerve probabilistic tractography can help the surgical strategy in a series of various skull base tumors. After distortion correction and region of interest seeding, a probabilistic tractography algorithm used the constrained spherical deconvolution model and attempted the reconstruction of cranial nerve trajectories in both healthy and displaced conditions. Sixty-two patients were included and presented: vestibular schwannomas (n=33); cerebellopontine angle meningiomas (n=15); arachnoid or epidermoid cysts (n=6); cavernous sinus and lower nerves schwannomas (n=4); and other tumors (n=4). For each patient, at least one 'displaced' cranial nerve was not clearly identified on classical anatomical MRI images. All 372 cranial nerves were successfully tracked on each healthy side; among the 175 cranial nerves considered 'displaced' by tumors, 152 (87%) were successfully tracked. Among the 127 displaced nerves of operated patients (n=51), their position was confirmed intraoperatively for 118 (93%) of them. Conditions that led to tractography failure were detailed. On the basis of tractography, the surgical strategy was adjusted for 44 patients (71%). This study reports a cranial nerve probabilistic tractography pipeline that can: predict the position of most cranial nerves displaced by skull base tumors, help the surgical strategy, and thus be a pertinent tool for future routine clinical application.

Full tractography for detecting the position of cranial nerves in preoperative planning for skull base surgery: technical note.

Diffusion imaging tractography has allowed the in vivo description of brain white matter. One of its applications is preoperative planning for brain tumor resection. Due to a limited spatial and angular resolution, it is difficult for fiber tracking to delineate fiber crossing areas and small-scale structures, in particular brainstem tracts and cranial nerves. New methods are being developed but these involve extensive multistep tractography pipelines including the patient-specific design of multiple regions of interest (ROIs). The authors propose a new practical full tractography method that could be implemented in routine presurgical planning for skull base surgery. A Philips MRI machine provided diffusion-weighted and anatomical sequences for 2 healthy volunteers and 2 skull base tumor patients. Tractography of the full brainstem, the cerebellum, and cranial nerves was performed using the software DSI Studio, generalized-q-sampling reconstruction, orientation distribution function (ODF) of fibers, and a quantitative anisotropy-based generalized deterministic algorithm. No ROI or extensive manual filtering of spurious fibers was used. Tractography rendering was displayed in a tridimensional space with directional color code. This approach was also tested on diffusion data from the Human Connectome Project (HCP) database. The brainstem, the cerebellum, and the cisternal segments of most cranial nerves were depicted in all participants. In cases of skull base tumors, the tridimensional rendering permitted the visualization of the whole anatomical environment and cranial nerve displacement, thus helping the surgical strategy. As opposed to classical ROI-based methods, this novel full tractography approach could enable routine enhanced surgical planning or brain imaging for skull base tumors.

Test-Retest Reliability of Diffusion Measures Extracted Along White Matter Language Fiber Bundles Using HARDI-Based Tractography.

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language.

Fiber tractography using machine learning

We present a fiber tractography approach based on a random forest classification and voting process, guiding each step of the streamline progression by directly processing raw diffusion-weighted signal intensities. For comparison to the state-of-the-art, i.e. tractography pipelines that rely on mathematical modeling, we performed a quantitative and qualitative evaluation with multiple phantom and in vivo experiments, including a comparison to the 96 submissions of the ISMRM tractography challenge 2015. The results demonstrate the vast potential of machine learning for fiber tractography.

Beyond crossing fibers: bootstrap probabilistic tractography using complex subvoxel fiber geometries.

Diffusion magnetic resonance imaging fiber tractography is a powerful tool for investigating human white matter connectivity in vivo. However, it is prone to false positive and false negative results, making interpretation of the tractography result difficult. Optimal tractography must begin with an accurate description of the subvoxel white matter fiber structure, includes quantification of the uncertainty in the fiber directions obtained, and quantifies the confidence in each reconstructed fiber tract. This paper presents a novel and comprehensive pipeline for fiber tractography that meets the above requirements. The subvoxel fiber geometry is described in detail using a technique that allows not only for straight crossing fibers but for fibers that curve and splay. This technique is repeatedly performed within a residual bootstrap statistical process in order to efficiently quantify the uncertainty in the subvoxel geometries obtained. A robust connectivity index is defined to quantify the confidence in the reconstructed connections. The tractography pipeline is demonstrated in the human brain.

Tractometer: Towards validation of tractography pipelines

We have developed the Tractometer: an online evaluation and validation system for tractography processing pipelines. One can now evaluate the results of more than 57,000 fiber tracking outputs using different acquisition settings (b-value, averaging), different local estimation techniques (tensor, q-ball, spherical deconvolution) and different tracking parameters (masking, seeding, maximum curvature, step size). At this stage, the system is solely based on a revised FiberCup analysis, but we hope that the community will get involved and provide us with new phantoms, new algorithms, third party libraries and new geometrical metrics, to name a few. We believe that the new connectivity analysis and tractography characteristics proposed can highlight limits of the algorithms and contribute in solving open questions in fiber tracking: from raw data to connectivity analysis. Overall, we show that (i) averaging improves quality of tractography, (ii) sharp angular ODF profiles helps tractography, (iii) seeding and multi-seeding has a large impact on tractography outputs and must be used with care, and (iv) deterministic tractography produces less invalid tracts which leads to better connectivity results than probabilistic tractography.