Research progress on the application of DTI in amyotrophic lateral sclerosis

  Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease involving upper and lower motor neurons. Diffusion tensor imaging (DTI) is a new imaging method developed on the basis of diffusion-weighted imaging, which can reflect the changes in the fine structure of tissues and can evaluate the damage of upper motor neurons more objectively.  The diagnosis of amyotrophic lateral sclerosis (ALS) is mainly based on EI Escorial clinical criteria [1 2], combined with electrophysiological changes and excluding other diseases, among which lower motor neuron (LMN) involvement can be diagnosed by electromyography, while upper motor neuron (UMN) damage mainly relies on clinical examination and lacks objective evaluation criteria. There is a lack of objective evaluation criteria. Conventional MRI can show early motor system atrophy, especially in the pyramidal tract, but it is difficult to quantify and does not provide a sensitive indicator of disease progression, and thus has significant limitations.  Diffusion tensor imaging (DTI) is a functional MRI technique developed in recent years based on diffusion weighted imaging (DWI), which can non-invasively study the anatomy and degeneration of the corticospinal tract (CST) and may be used as an objective morphological indicator for clinical treatment trials. The progress in recent years is reviewed as follows.  I. DTI images of the normal corticospinal tract DTI is a new method to study the CST in ALS patients. The corticospinal tract is a white matter bundle with obvious morphological changes, consisting of axonal fibers from large cone cells in the cerebral cortex, which descends through the posterior limb of the internal capsule to the base of the cerebral peduncle in the midbrain, occupying the lateral part of its middle 3/5; then to the base of the cerebral bridge, dispersing into fiber bundles of different sizes downward; to the conus medullaris, the fibers are gathered together again to form a bundle. At the inferior end of the conus, most of the fibers (about 70%-90%) cross each other, forming a conus intersection. The crossed fibers descend to the posterior lateral part of the lateral cord of the contralateral spinal cord, forming the lateral corticospinal tract, which terminates one after another at the anterior horn cells of the spinal cord in the process of descending; a small number of fibers do not cross and enter the anterior cord of the spinal cord, forming the anterior corticospinal tract, the fibers of which terminate at the anterior horn motor cells of the contralateral spinal cord via the anterior white matter conjoined cross section by section. The degree of variability in the tightness of these bundles will reflect the greater variability in fractional anisotropy (FA) values on the CST alignment.  DTI measures the diffuse movement of water molecules, which is influenced by the characteristics of the cells themselves and the cellular structures that impede the movement of water molecules. The anisotropy of cerebral white matter, cerebral gray matter, and cerebrospinal fluid differs depending on the characteristics of the cells themselves and the cellular structures that impede the movement of water molecules, and thus appear as different grayscale images on the DTI image. Most of the major fiber tracts in the white matter can be identified in the FA map. On the FA map of normal DTI, normal white matter appears as high signal, and the alignment of major fiber bundles in the white matter of the brain, such as the corpus callosum, internal capsule, external capsule, and pyramidal bundles, can be identified.  Partial anisotropy and mean diffusivity (MD) values varied greatly at different anatomical levels, with a gradual decrease in FA from the cerebral peduncle to the conus, with the highest FA values at the cerebral peduncle and the lowest FA values below the level of the cerebral bridge. FA was also highly variable at adjacent levels from the cerebral bridge to the medulla, but the mean FA values were the same at all levels at the cerebral peduncle; MD tended to increase from the internal capsule to the conus, with the highest MD values at the medulla and the lowest at the cerebral bridge. At the pons CST fibers separated into multiple branches that crossed each other laterally across the pons were not as dense as those above the pons, resulting in lower FA and higher MD (because of higher water dispersion rates due to increased extracellular volume). From the cerebral peduncle to the conus, many fibers leave the CST, with indirect fibers leaving various brainstem nuclei at the site of the cerebral bridge, and 20 million fibers on the cerebral peduncle side, while the conus side is composed of only 1 million fibers; although motor tracts are more concentrated in the conus, the small size of the vertebral body and the restrictive nature of ROI (region of interest) analysis imply that from the adjacent multidirectional fiber tracts to other brainstem nuclei, the adjacent cerebrospinal fluid and the interruption of fiber coherence by cone crossings, which combine to result in lower FA and higher MD [10].Schimrigk SK and Sage CA et al. advocated setting the ROI caudal to the posterior limb of the internal capsule where fibers are highly concentrated.Sage CA et al. found reduced FA in the periventricular white matter because superior longitudinal tracts and corpus callosum fibers (perpendicular to the horizontal CST course) at this site emerged, and their different diffusion principal directions led to a decrease in FA, whereas MD was not affected by the mean diffusion direction and thus did not change significantly at the periventricular level.  The region of interest (ROI) method, which is currently used for DTI studies, has the advantage that specific parts of the brain can be accurately localized (e.g., the pyramidal tract), but also has the disadvantage that artificial localization on the CST image of interest is subjective to the investigator. Partial volume contamination) is the most common concern. The use of fiber-tracking imaging (fibertracking) to select ROI can avoid the influence of the investigator’s own factors, provide fiber-track reconstruction, and the quantitative analysis obtained from this method can better quantify and compare the diffusion characteristics between the two groups, providing more information about the white matter structure and more objective evaluation of white matter integrity than the FA map of ROI. Fiber imaging is an excellent tool for elucidating white matter fiber alignment, but is not applicable to volumetric analysis (volumetric analysis). Fiber imaging varies according to FA, image clarity in the ROI region, and signal-to-noise ratio, so the authors concluded that the quantitative evaluation of CST volume obtained using fiber imaging is inaccurate, but the technique can be used to image specific regions of the CST, but cannot completely overcome some of the volumetric effects of ROI analysis, requiring higher resolution DTI equipment and new techniques related to DTI: diffusion spectrum imaging (DSI). diffusion spectrum imaging (DSI).  In view of the shortcomings of ROI, Schimrigk SK introduced a new method: the probabilistic mixture model to improve the accuracy of DTI parameters, which directly quantifies the DTI data and can automatically classify the pixels in the ROI region into fiber, non-fiber (background) and mixed states, allowing the pure fibers in the mixture to be separation, even if the fiber bundles are very close to each other. This method minimizes the influence of personal factors of the researcher on the results. The results have been validated in the corpus callosum.  Foreign studies on the application of DTI in amyotrophic lateral sclerosis have focused on the region of interest (ROI) of the corticospinal tracts in the corona radiata, the posterior limb of the internal capsule, the peduncle, the pons, and the pyramidal cones of the medulla oblongata. In DTI images of ALS, most of the literature reports changes in the diffusion values of CST: decreased FA values and increased ADC/MD values, especially at the level of the posterior limb of the internal capsule.Schimrigk SK suggests that the identification of healthy subjects with ALS should be chosen from the internal capsule, which has the least variation and the greatest difference, and FA <0.57/0.55 can be considered abnormal if age is not taken into account.