Non-invasive flow mapping of parasagittal meningeal lymphatics using 2D interslice flow saturation MRI

Abstract

The clearance pathways of brain waste products in humans are still under debate in part due to the lack of noninvasive imaging techniques for meningeal lymphatic vessels (mLVs). In this study, we propose a new noninvasive mLVs imaging technique based on an inter-slice blood perfusion MRI called alternate ascending/descending directional navigation (ALADDIN). ALADDIN with inversion recovery (IR) at single inversion time of 2300 ms (single-TI IR-ALADDIN) clearly demonstrated parasagittal mLVs around the human superior sagittal sinus (SSS) with better detectability and specificity than the previously suggested noninvasive imaging techniques. While in many studies it has been difficult to detect mLVs and confirm their signal source noninvasively, the detection of mLVs in this study was confirmed by their posterior to anterior flow direction and their velocities and morphological features, which were consistent with those from the literature. In addition, IR-ALADDIN was compared with contrast-enhanced black blood imaging to confirm the detection of mLVs and its similarity. For the quantification of flow velocity of mLVs, IR-ALADDIN was performed at three inversion times of 2000, 2300, and 2600 ms (three-TI IR-ALADDIN) for both a flow phantom and humans. For this preliminary result, the flow velocity of the dorsal mLVs in humans ranged between 2.2 and 2.7 mm/s. Overall, (i) the single-TI IR-ALADDIN can be used as a novel non-invasive method to visualize mLVs in the whole brain with scan time of ~ 17 min and (ii) the multi-TI IR-ALADDIN can be used as a way to quantify the flow velocity of mLVs with a scan time of ~ 10 min (or shorter) in a limited coverage. Accordingly, the suggested approach can be applied to noninvasively studying meningeal lymphatic flows in general and also understanding the clearance pathways of waste production through mLVs in humans, which warrants further investigation.

Keywords: ALADDIN; Flow velocity; Magnetic resonance imaging; Meningeal lymphatic vessel; Non-invasive; Parasagittal; Perfusion imaging.

Fig. 1

a Anatomical structure of parasagittal meningeal lymphatics, b IR-ALADDIN imaging scheme and c IR-ALADDIN sequence diagram. IR-ALADDIN Inversion-recovery alternate ascending/descending directional navigation, mLVs Meningeal lymphatic vessels, CSF Cerebrospinal fluid, GM Gray matter, WM White matter, SSS Superior sagittal sinus, PSD Parasagittal dura mater

Fig. 2

Flow phantom setting scheme, a Diagram of flow phantom, infusion pump and coronal IR-ALADDIN slices. Water flows into the tube from the infusion pump and flows out to the water tank outside of MRI room. b Minimum intensity projection of phantom 3D T1 images

Fig. 3

IR-ALADDIN signal intensity simulation. Simulation results with varying inversion time for different tissues, a plot of baseline signal intensity, b plot of relative signal changes from PSC and subtraction. Simulation results of relative percent signal changes of lymphatic flow with c varying slice gap (dotted line: relaxation time varies − 10–10%) and d varying inversion time. Relative signal change: relative ratio of percent signal changes. mLVs : meningeal lymphatic vessels with flow velocity of 1 mm/s for (a) and (b), CSF Cerebrospinal fluid with net flow velocity of 0 mm/s, SSS Superior sagittal sinus with flow velocity of 13 cm/s, Arteriole Arteriole with flow velocity of 10 mm/s

Fig. 4

IR-ALADDIN images of flow phantom. a, d Baseline images of flow phantom, b, c subtracted images at flow velocity 1.3 mm/s, e, f PSC images at flow velocity 1.3 mm/s

Fig. 5

IR-ALADDIN PSC results of the flow phantom experiment. PSC as a function of flow velocity measured with inversion time of a 2000 ms, b 2300 ms, and c 2600 ms, of the in-plane tube. Black cross points represent raw PSC signal from multiple slices. Orange dots represent average PSC from multiple slices. d PSCs as a function of flow velocity measured at all inversion times. e IR-ALADDIN signal intensity simulation at different inversion times. PSC: percent signal change

Fig. 6

Representative image of IR-ALADDIN. a, d Subtraction images, b–e PSC images, c Anatomical baseline image, f Merged bidirectional image (anterior to posterior and posterior to anterior), g 3D reconstructed IR-ALADDIN with brain tissue (orange), venous vessels (blue) and meningeal lymphatic vessels (green). PSC Percent signal change

Fig. 7

The box plot of percent signal change (PSC) of SSS, mLVs, GM and CSF from the PSC image. Positive PSC represents the A→P direction and negative PSC represents the P→A direction of IR-ALADDIN images. Cross points represent the mean PSC of each tissue, and outliers were pointed in circle outside of the boxes. SSS Superior sagittal sinus, mLVs Meningeal lymphatic vessels, GM Gray matter, CSF Cerebrospinal fluid

Fig. 8

Preliminary results of in-vivo multi TI IR-ALADDIN experiment. a P→A directional PSC images from different inversion times. Red boxes represent the region of parasagittal mLVs. b Averaged PSCs from different inversion times and 4 healthy subjects. PSC Percent signal change (%)

Fig. 9

Representative images for visual comparison between IR-ALADDIN mLVs image and contrast-enhanced black blood mLVs images with pre/post injection. a IR-ALADDIN baseline image, b mLVs image from IR-ALADDIN with flow direction of P→A, c, d Black blood images with pre and post injection, e subtracted image between post and pre-injection black blood images. Red arrows represent brightened mLVs structures. mLVs : meningeal lymphatic vessels

Fig. 10

Comparison of mLVs images between FLAIR, IR-ALADDIN, and TOF in the same imaging position. Yellow boxes indicate the location of mLVs around the SSS