Imaging Interstitial Fluid With MRI: A Narrative Review on the Associations of Altered Interstitial Fluid With Vascular and Neurodegenerative Abnormalities

Abstract

Interstitial fluid (ISF) refers to the fluid between the parenchymal cells and along the perivascular spaces (PVS). ISF plays a crucial role in delivering nutrients and clearing waste products from the brain. This narrative review focuses on the use of MRI techniques to measure various ISF characteristics in humans. The complementary value of contrast‐enhanced and noncontrast‐enhanced techniques is highlighted. While contrast‐enhanced MRI methods allow measurement of ISF transport and flow, they lack quantitative assessment of ISF properties. Noninvasive MRI techniques, including multi‐b‐value diffusion imaging, free‐water‐imaging, T2‐decay imaging, and DTI along the PVS, offer promising alternatives to derive ISF measures, such as ISF volume and diffusivity. The emerging role of these MRI techniques in investigating ISF alterations in neurodegenerative diseases (eg, Alzheimer's disease and Parkinson's disease) and cerebrovascular diseases (eg, cerebral small vessel disease and stroke) is discussed. This review also emphasizes current challenges of ISF imaging, such as the microscopic scale at which ISF has to be measured, and discusses potential focus points for future research to overcome these challenges, for example, the use of high‐resolution imaging techniques. Noninvasive MRI methods for measuring ISF characteristics hold significant potential and may have a high clinical impact in understanding the pathophysiology of neurodegenerative and cerebrovascular disorders, as well as in evaluating the efficacy of ISF‐targeted therapies in clinical trials.Level of Evidence3Technical EfficacyStage 2

Overview of the Current Knowledge and Conventional MRI Characteristics of Peri- and Para-Vascular Spaces

“…The DTI-ALPS technique has been widely employed in studies involving aging and small vessel disease cohorts. In all instances, a consistent finding emerged, indicating an inverse correlation between the load of WMH and the diffusion of venous interstitial fluid in the PVS [48]. Research using the DTI-ALPS approach additionally demonstrated diminished fluid dynamics in the venous PVS following occurrences of ischemic stroke [72] and intracerebral hemorrhage [73].…”

“…To address non-specificity in DTI interpretations, a multi-compartment modeling approach is employed. This involves acquiring diffusion-weighted images at various b-values or gradient strengths to probe different tissue compartments characterized by distinct diffusion profiles [48]. Examining the diffusion of interstitial fluid within the PVS provides valuable insights into the PVS microstructure, including pathological enlargement and function, such as disruptions in glymphatic flow due to debris presence.…”