Systems and Methods for Measuring Global Glymphatic Flow Using Magnetic Resonance Imaging

Abstract

Systems and methods for providing quantitative measurements of global glymphatic flow of cerebrospinal fluid (“CSF”) using magnetic resonance imaging (“MRI”) are described. In general, images are obtained from a subject using flow-sensitive MRI techniques that are designed to be particularly sensitive to the glymphatic flow of CSF. Measures of glymphatic flow can be obtained while the subject is in an awake state and again while the subject is in a sleep state. Based on these two measurements, a biomarker that indicates a neurological state or disease can be generated.

1 . A method for measuring glymphatic flow in a subject using a magnetic resonance imaging (MRI) system, the steps of the method comprising:
 (a) directing the MRI system to acquire data from a subject using a pulse sequence that induces an image contrast in the acquired data that is associated with glymphatic flow;   (b) reconstructing at least one image from the data acquired in step (a); and   (c) estimating a measure of global glymphatic flow from the at least one image reconstructed in step (b).   
     
     
         2 . The method as recited in  claim 1 , further comprising administering a contrast agent to a subject's cerebrospinal fluid, and wherein step (a) includes performing a contrast-enhanced pulse sequence. 
     
     
         3 . The method as recited in  claim 2 , wherein step (a) is performed while the contrast agent is perfusing through tissues in the subject. 
     
     
         4 . The method as recited in  claim 3 , wherein step (b) includes reconstructing a series of images and step (c) includes computing at least one signal intensity curve from the series of images and estimating the measure of global glymphatic flow from the at least one signal intensity curve. 
     
     
         5 . The method as recited in  claim 4 , wherein the measure of global glymphatic flow is estimated from the at least one signal intensity curve using a perfusion contrast kinetics model. 
     
     
         6 . The method as recited in  claim 2 , wherein step (a) is performed while the contrast agent is flowing through a central nervous system of the subject. 
     
     
         7 . The method as recited in  claim 1 , wherein step (a) includes:
 acquiring spin-labeled data from an imaging region in the subject by applying a radio frequency (RF) pulse to a labeling region in the subject that is proximal to the imaging region, such that spins associated with cerebrospinal fluid are labeled and flow into the imaging region while the spin-labeled data is acquired;   acquiring control data from the imaging region in the subject, wherein an RF pulse is not applied to the labeling region prior to acquiring the control data from the imaging region.   
     
     
         8 . The method as recited in  claim 7 , wherein step (b) includes reconstructing a control image from the control data and a labeled image from the spin-labeled data, and wherein step (c) includes estimating the measure of global glymphatic flow from a difference image produced by subtracting the control image and the labeled image. 
     
     
         9 . The method as recited in  claim 1 , wherein step (a) includes performing a phase contrast pulse sequence that is configured to impart a phase contrast to cerebrospinal fluid flowing though the subject's central nervous system. 
     
     
         10 . The method as recited in  claim 9 , wherein step (a) includes acquiring multiple different sets of data, each set of data being acquired using different flow-encoding gradients in the phase contrast pulse sequence such that different states of glymphatic flow are sensitized.