There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood–brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field.Evidence Level: 3Technical Efficacy: Stage 5

Diffusion magnetic resonance imaging tractography is a noninvasive technique that enables the visualization and quantification of white matter tracts within the brain. It is extensively used in preoperative planning for brain tumors, epilepsy, and functional neurosurgical procedures such as deep brain stimulation. Over the past 25 years, significant advancements have been made in imaging acquisition, fiber direction estimation, and tracking methods, resulting in considerable improvements in tractography accuracy. The technique enables the mapping of functionally critical pathways around surgical sites to avoid permanent functional disability. When the limitations are adequately acknowledged and considered, tractography can serve as a valuable tool to safeguard critical white matter tracts and provides insight regarding changes in normal white matter and structural connectivity of the whole brain beyond local lesions. In functional neurosurgical procedures such as deep brain stimulation, it plays a significant role in optimizing stimulation sites and parameters to maximize therapeutic efficacy and can be used as a direct target for therapy. These insights can aid in patient risk stratification and prognosis. This article aims to discuss state-of-the-art tractography methodologies and their applications in preoperative planning and highlight the challenges and new prospects for the use of tractography in daily clinical practice.

Background and purpose: Exposure to contact sports in youth causes brain health problems later in life. For instance, the repetitive head impacts in contact sports might contribute to glymphatic clearance impairment and cognitive decline. This study aimed to assess the effect of contact sports participation in youth on glymphatic function in old age and the relationship between glymphatic function and cognitive status using the analysis along the perivascular space (ALPS) index.Materials and methods: A total of 52 Japanese older male subjects were included in the study, including 12 who played heavy-contact sports (mean age, 71.2 years), 15 who played semicontact sports (mean age, 73.1 years), and 25 who played noncontact sports (mean age, 71.3 years) in their youth. All brain diffusion-weighted images (DWIs) of the subjects were acquired using a 3T MRI scanner. The ALPS indices were calculated using a validated semiautomated pipeline. The ALPS indices from the left and right hemispheres were compared between groups using a general linear model, including age and years of education. Furthermore, partial Spearman's rank correlation tests were performed to assess the correlation between the ALPS indices and cognitive scores (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment [MoCA-J]) after adjusting for age years of education and HbA1c.Results: The left ALPS index was significantly lower in the heavy-contact and semicontact groups than that in the noncontact group. Although no significant differences were observed in the left ALPS index between the heavy-contact and semicontact groups and in the right ALPS index among groups, a trend toward lower was found in the right ALPS index in individuals with semicontact and heavy-contact compared to the noncontact group. Both sides' ALPS indices were significantly positively correlated with the MoCA-J scores.Conclusion: The findings indicated the potential adverse effect of contact sports experience in youth on the glymphatic system function in old age associated with cognitive decline.