Reconstructing the somatotopic organization of the corticospinal tract remains a challenge for modern tractography methods.

The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. The CST exhibits a somatotopic organization, which means that the motor neurons that control specific body parts are arranged in order within the CST. Diffusion magnetic resonance imaging (MRI) tractography is increasingly used to study the anatomy of the CST. However, despite many advances in tractography algorithms over the past decade, modern, state-of-the-art methods still face challenges. In this study, we compare the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. These methods include constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, unscented Kalman filter (UKF) tractography methods including multi-fiber (UKF2T) and single-fiber (UKF1T) models, the generalized q-sampling imaging (GQI) based deterministic tractography method, and the TractSeg method. We investigate CST somatotopy by dividing the CST into four subdivisions per hemisphere that originate in the leg, trunk, hand, and face areas of the primary motor cortex. A quantitative and visual comparison is performed using diffusion MRI data (N = 100 subjects) from the Human Connectome Project. Quantitative evaluations include the reconstruction rate of the eight anatomical subdivisions, the percentage of streamlines in each subdivision, and the coverage of the white matter-gray matter (WM-GM) interface. CST somatotopy is further evaluated by comparing the percentage of streamlines in each subdivision to the cortical volumes for the leg, trunk, hand, and face areas. Overall, UKF2T has the highest reconstruction rate and cortical coverage. It is the only method with a significant positive correlation between the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex. However, our experimental results show that all compared tractography methods are biased toward generating many trunk streamlines (ranging from 35.10% to 71.66% of total streamlines across methods). Furthermore, the coverage of the WM-GM interface in the largest motor area (face) is generally low (under 40%) for all compared tractography methods. Different tractography methods give conflicting results regarding the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex, indicating that there is generally no clear relationship, and that reconstruction of CST somatotopy is still a large challenge. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face areas) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.

Fiber-specific white matter alterations in Parkinson's disease patients with freezing of gait.

Freezing of gait (FOG) is a gait disorder that usually occurs in advanced stages of Parkinson's disease (PD). Understanding the underlying mechanism of FOG is important for treatment and prevention. Previous studies have investigated white matter (WM) structure to explore the pathology of FOG. However, the pathology is still unclear, possibly due to the methodological limitation in identifying specific fiber tracts. This study aimed to investigate tract-specific WM structural changes in FOG patients and their relationships with clinical characteristics. We enrolled 19 PD patients with FOG (PD-FOG), 19 without FOG (PD-woFOG) and 21 controls. Fixel-based analysis is a novel framework to avoid the effect of crossing fibers, which provides the metrics to assess WM morphology. By combining a method for segmenting fibers, we identified abnormalities in the specific fiber tracts. Compared to PD-woFOG, PD-FOG showed significant increased fiber-bundle cross-section (FC) in the corpus callosum (CC), fornix (FX), inferior longitudinal fasciculus (ILF), striato-premotor (ST_PREM), superior thalamic radiation (STR), thalamo-premotor (T_PREM), increased fiber density and cross-section (FDC) in the STR, and decreased fiber density (FD) in the CC and ILF. Additionally, the ILF was correlated with motor, cognition and memory, the CC was correlated with anxiety, and the T_PREM was also correlated with cognition. In conclusion, in addition to impairments of WM found in PD-FOG, we found enhancements in WM, which may imply compensatory mechanisms. Furthermore, multiple fiber tracts were correlated with clinical characteristics, especially the ILF, validating the involvement of transmission circuits of multiple distinct information in mechanisms of FOG.

A unified global tractography framework for automatic visual pathway reconstruction.

The human visual pathway starts from the retina, passes through the retinogeniculate visual pathway, the optic radiation, and finally connects to the primary visual cortex. Diffusion MRI tractography is the only technology that can noninvasively reconstruct the visual pathway. However, complete and accurate visual pathway reconstruction is challenging because of the skull base environment and complex fiber geometries. Specifically, the optic nerve within the complex skull base environment can cause abnormal diffusion signals. The crossing and fanning fibers at the optic chiasm, and a sharp turn of Meyer's loop at the optic radiation, contribute to complex fiber geometries of the visual pathway. A fiber trajectory distribution (FTD) function-based tractography method of our previous work and several high sensitivity tractography methods can reveal these complex fiber geometries, but are accompanied by false-positive fibers. Thus, the related studies of the visual pathway mostly applied the expert region of interest selection strategy. However, interobserver variability is an issue in reconstructing an accurate visual pathway. In this paper, we propose a unified global tractography framework to automatically reconstruct the visual pathway. We first extend the FTD function to a high-order streamline differential equation for global trajectory estimation. At the global level, the tractography process is simplified as the estimation of global trajectory distribution coefficients by minimizing the cost between trajectory distribution and the selected directions under the prior guidance by introducing the tractography template as anatomic priors. Furthermore, we use a deep learning-based method and tractography template prior information to automatically generate the mask for tractography. The experimental results demonstrate that our proposed method can successfully reconstruct the visual pathway with high accuracy.