Preliminary investigations into human neurofluid transport using multiple novel non-contrast MRI methods

Abstract

We discuss two potential non-invasive MRI methods to study phenomena related to subarachnoid cerebrospinal fluid (CSF) motion and perivascular fluid transport, and their association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or CSF movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and trans-endothelial exchange (T_ex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N = 9, 6 F, 23 ± 3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults (6 F, 67 ± 3 years old) were imaged after a night of normal sleep and compared with the young adults. D* in SAS was significantly (p < 0.05) reduced with sleep deprivation (0.016 ± 0.001 mm²/s) compared to normal sleep (0.018 ± 0.001 mm²/s) and marginally reduced with aging (0.017 ± 0.001 mm²/s, p = 0.029). Cortical CBF and T_ex were unchanged with sleep deprivation but significantly lower in older adults (37 ± 3 ml/100 g/min, 578 ± 61 ms) than in young adults (42 ± 2 ml/100 g/min, 696 ± 62 ms). IVIM was sensitive to sleep physiology and aging, and multi-echo, multi-delay ASL was sensitive to aging.

Keywords: ASL; IVIM; Neurofluid water transport; aging; glymphatic transport; sleep.

Figure 1.

(a) IVIM acquisition involves multi-b value acquisition in at least 3 directions. Our acquisition used 6 directions. 12 b-values (10, 20, 40, 80, 100, 150, 200, 300, 500, 700, 900, 1000 s/mm²) were used. The two exponentials corresponding to the 2 diffusion regimes are shown in blue and green. Blue corresponds to D*, with faster diffusion reflecting water movement over long distances, and green corresponds to D, with slow diffusion reflecting water movement over short distances. Parametric maps for D*, D, and f, tin the whole brain of one participant, are shown in b, c, and d, respectively.

Figure 2.

The top row shows the M0 reference image in grayscale. The bottom 3 rows show ASL difference images for each of the post-labeling delay times 650, 1218, and 2089 ms. Each echo time is shown along the columns.

Figure 3.

(a) IVIM parameters, D*, D, and f in older adults (first column), in young adults with normal sleep (middle column), and the same young adults with sleep deprivation (third column) in the SAS. (b) D* values in all three groups: young adults after a night of normal sleep (blue), young adults after 24 hours of sleep deprivation (yellow), and older adults after normal sleep (red). (c) Only D* was significantly different (p = 0.006) after 24 hours of sleep deprivation compared to a night of normal sleep and (d, e) D, and f values in all three groups: young adults after a night of normal sleep (blue), young adults after 24 hours of sleep deprivation (yellow), and older adults after normal sleep (red). No difference was observed with aging. Supplementary Figure 1 shows the ROIs generated for this study.

Figure 4.

(a) ASL parameters, Whole-brain cortical CBF, and T_ex in older adults (first column), in young adults with normal sleep (middle column), and the same young adults with sleep deprivation (third column). CBF was not significantly different in young adults after sleep deprivation (yellow) compared to those after a night of normal sleep (blue). Detailed paired comparison is shown in (b) CBF was significantly different in older adults (red) compared to young adults (p = 0.005) and (c) T_ex was also not significantly different in young adults after sleep deprivation (yellow) compared to those after a night of normal sleep (blue). Like CBF, T_ex was significantly shorter in older adults (red) than in young adults (p = 0.0001).