Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity

Author: Koji Kamagata1, Yuya Saito1, Christina Andica1,2, Wataru Uchida1, Kaito Takabayashi1, Seina Yoshida1,3, Akifumi Hagiwara1, Shohei Fujita1,4, Moto Nakaya1,4, Toshiaki Akashi1, Akihiko Wada1, Kouhei Kamiya5, Masaaki Hori5, Shigeki Aoki1,2
1 Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
2 Faculty of Health Data Science, Juntendo University, Chiba, Japan.
3 Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
4 Department of Radiology, The University of Tokyo, Tokyo, Japan.
5 Department of Radiology, Toho University Omori Medical Center, Tokyo, Japan.
Conference/Journal: J Magn Reson Imaging
Date published: 2023 Sep 1
Other: Special Notes: doi: 10.1002/jmri.28977. , Word Count: 312

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: 3 TECHNICAL EFFICACY: Stage 5.

Keywords: blood-brain barrier; glymphatic system; interstitial fluid; noninvasive MRI techniques; perivascular space.

PMID: 37655849 DOI: 10.1002/jmri.28977