Age-related Decline of Intrinsic Cerebrospinal Fluid Outflow in Healthy Humans Detected with Non-contrast Spin-labeling MR Imaging

Abstract

Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implications for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on venous or invasive intrathecal injections of contrast agents. The objective of this study was to introduce a novel spin-labeling MRI technique to detect and quantify the movement of endogenously tagged CSF, and then apply it to evaluate CSF outflow in normal humans of varying ages.Methods: This study was performed on a clinical 3-Tesla MRI scanner in 16 healthy subjects with an age range of 19-71 years with informed consent. Our spin-labeling MRI technique applies a tag pulse on the brain hemisphere, and images the outflow of the tagged CSF into the superior sagittal sinus (SSS). We obtained 3D images in real time, which was analyzed to determine tagged-signal changes in different regions of the meninges involved in CSF outflow. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics. These were correlated against subject age to determine aging effects. Results:We observed the signal of the tagged CSF moving from the dura mater and parasagittal dura, and finally draining into the SSS. In addition, we observed a possibility of another pathway which is seen in some young subjects. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age. Conclusion:We demonstrate a novel non-invasive MRI technique identifying two intrinsic CSF clearance pathways, and observe an age-related decline of CSF flow metrics in healthy subjects. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways during the aging process, which may ultimately provide insight into the age-related prevalence of neurodegenerative diseases.

Physical Exercise Alters Egress Pathways for Intrinsic CSF Outflow: An Investigation Performed with Spin-labeling MR Imaging

“…17 However, to improve the accuracy of signal increase ratio (SIR) curve fitting, the temporal resolution near inversion time (TI) = 1250 ms was increased since the preliminary scans showed it to be the TI where the peak flow occurs. 17 In a total, we collected 9 temporal points (9 TIs). Detailed methodology of time-resolved non-contrast MRI has been previously described by Malis et al 17 We used the simple subtraction of tag-off from the tag-on images to visualize intrinsic CSF moves out from the tagged region.…”

“…17 In a total, we collected 9 temporal points (9 TIs). Detailed methodology of time-resolved non-contrast MRI has been previously described by Malis et al 17 We used the simple subtraction of tag-off from the tag-on images to visualize intrinsic CSF moves out from the tagged region. To elucidate quantitative metrics of intrinsic CSF outflow, SIR was calculated using SIR = |Tag-on -Tag-off|/|Tag-off| to observe a perfusion-like function.…”

“…A tag-on and tag-off alternate acquisition and subtraction technique was used with 3D cSSFSE. The detailed tag-on and tag-off 3D acquisitions were also described in the work by Malis et al, 17 as well as the applications in the non-contrast MR angiography and perfusion techniques. [27][28][29][30] Of note, we confirmed 17 that the technique measures CSF signal while suppressing blood signal by using a long effective TE of 300 ms, since the T2 of blood is shorter around 60 ms.…”

“…16 We previously introduced a novel MRI method for quantifying CSF outflow in humans that does not require injection of tracers, but instead uses spin-labeling MRI which can detect the perfusion-like movement of endogenously tagged CSF. 17 With this method, we showed net CSF outflow from the dura mater into the superior sagittal sinus (SSS) over a time period of less than 3 seconds. Our prior work detailed multiple potential but distinct anatomic pathways of glymphatic clearance in the brain.…”

Low <i>b</i>-value Diffusion Tensor Imaging to Analyze the Dynamics of Cerebrospinal Fluid: Resolving Intravoxel Pseudorandom Motion into Ordered and Disordered Motions

“…These techniques measure fluid motion by modifying the MR signal corresponding to the amount of water movement. Typical techniques include spin labeling (SL), [12][13][14][15] phase contrast (PC), [16][17][18][19][20][21][22] and diffusion-weighting (DW). [23][24][25][26][27][28] SL detects signals from spins excited in specific regions and outflows from the regions after a certain delay.…”