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Background: White matter (WM) fiber tracts in the brainstem communicate with various regions in the cerebrum, cerebellum, and spinal cord. Clinically, small lesions, malformations, or histopathological changes in the brainstem can cause severe neurological disorders. A direct and non-invasive assessment approach could bring valuable information about the intricate anatomical variations of the white matter fiber tracts and nuclei. Although tractography from diffusion tensor imaging has been commonly used to map the WM fiber tracts connectivity, it is difficult to differentiate the complex WM tracts anatomically. Both high field MRI methods and ultrahigh-field MRI methods at 7T and 11.7 T have been used to enhance the contrast of WM fiber tracts. Despite their promising results, it is still challenging to achieve wide clinical adoption at 3T. In this study, we explored a clinically feasible method using a proton density weighted (PDW) 3D gradient echo (GRE) sequence to directly image the WM fiber tracts in the brainstem at 3T in vivo. Methods: We optimized a 3D high resolution, double echo, short TR, PDW GRE sequence on 5 healthy volunteers using a clinical 3T scanner to visualize the complicated anatomy of WM fiber tracts in the brain stem. Tissue properties including T1, proton density and T2* from in vivo quantitative MRI data were used for simulations to determine the optimal flip angle for the sequence. The visualization of multiple WM fiber tracts in the brainstem was assessed qualitatively and quantitatively using relative contrast and contrast-to-noise ratio (CNR). To improve the CNR, the final images were created by averaging over all echoes from two consecutive scans at the optimal flip angle. The results were compared to anatomical atlases and histology sections to identify the major fiber tracts. All the identified major fiber tracts were labeled on axial, sagittal and coronal slices. Results: The WM fiber tracts were found to have distinct hypointense signal throughout the brainstem and most of the major WM fiber tracts, such as the corticospinal tract, medial lemniscus, medial longitudinal fasciculus, and central tegmental tract, in the brainstem up to and including the thalamus were identified in all subjects. Both qualitative and quantitative evaluations showed that the 3° scan offered the best contrast for WM fiber tracts for a TR of 20 ms. The average over the first two echo times and two consecutive 3° scans gave a CNR of 47.8 ± 6.2 for the pyramidal tracts in particular and CNRs values greater than 6.5 ± 2.4 for the rest of the fiber tracts. Conclusions: All the major fiber tracts in the brainstem could be visualized. Given the reasonably short scan time of 10 min at 3T, double echo PDW GRE sequence is a very practical approach for clinical adoption.

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the ''on medication'' state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.