Yongxian Qian1, Karthik Lakshmanan1, Yulin Ge1, Yvonne W. Lui1, Thomas Wisniewski2, and Fernando E. Boada1
1Radiology, New York University, New York, NY, United States, 2Neurology, New York University, New York, NY, United States
Synopsis
This study presents preliminary data to demonstrate the potential
of dynamic sodium MRI for mapping cerebrospinal fluid (CSF) bulk flow in extracellular
space of tissues in whole brain.
INTRODUCTION
Recent studies have shown that disruption of cerebrospinal fluid (CSF)
clearance of brain waste may contribute to development of Alzheimer’s disease
(AD) which is characterized by excessive toxic deposits in the brain. Studies
on mice demonstrated that impairment of CSF clearance led to 70% reduction in amyloid beta (Aβ) clearance1,2 while sleep-induced
enhancement of CSF flow increased Aβ clearance
by 100% 3. It is unclear whether these impairment and enhancement
exist in humans. Technical limitations on noninvasive in vivo approaches hinder
adequate study on this important issue. Specifically, phase-contrast (PC) MRI usually
measures CSF flow at aqueduct and ventricles, instead of brain tissues 4-7.
Contrast-enhanced (CE) MRI (including dynamic CE-MRI) only tracks CSF flow
along vasculature8,9. Low-b value diffusion tensor imaging (DTI)
assesses local flow of CSF in drainage 10-12. There’s no known proton
(1H)-based MRI approaches capable of distinguishing CSF from water
in the brain parenchyma when external tracer is not appropriate9,13.
Here we leverage the high concentration of sodium in CSF and interstitial fluid
in extracellular space against intracellular space in the parenchyma, and show
a dynamic sodium (23Na) MRI for mapping CSF bulk flow in tissues in whole
brain.METHODS
Sodium MR signal is from
sodium nuclei (23Na), not protons (1H), in tissues. CSF
has a high sodium concentration of 145mM, which is nearly 10 times that in
intracellular space (15mM) of human brain14 and can be more
reliably measured. CSF exclusively occupies extracellular space in brain parenchyma
and self-serves as an endogenous tracer on sodium imaging for bulk flow driven
by pulsation. Sodium signal at an imaging voxel is defined (Eq. 1) by the
voxel volume ∆V and intra-/extracellular volume fraction a and sodium concentration C.
Any change in extracellular space ae
is amplified by a factor of 130 (=145-15) and leads to a scaled-up variation in
signal (Eq. 2 and Fig. 1).
Eq. 1: s = ΔV (aeCe + aiCi) = ΔV (145 ae + 15 ai),
Eq. 2: Δs = ΔV [ Δae (Ce - Ci) + Ci] = ΔV (130 ae + 15).
Dynamic sodium MRI employed an interleaved-viewing
scheme in data acquisition to achieve a high temporal resolution (9.0 sec). To compensate for its intrinsically
low signal-to-noise ratio (SNR), the sodium MRI used an SNR-efficient 3D trajectory,
the twisted projection imaging (TPI)15, for data acquisition (Figs. 2a,b). Each frame has an independent full sampling of the k-space.
Velocity map (vector field) of CSF bulk flow was created based on the frame
images using an open-source software OpenPIV (Particle Image Velocimetry, v2.5)16.
It calculates pixel velocity between time frames using a correlation between image
patches in an interrogation window centered at the pixel.
Numerical simulations
were also performed to calculate sodium MR signal at a pixel with a given intensity varying
with time at a range of frequencies of interest. EXPERIMENTS
Two male subjects of age 27 and 72 years were studied on a 3T MRI scanner (Prisma, Siemens) with a custom-built 8-channel dual-tuned (1H-23Na)
head array coil17. Approved IRB and written consent forms were obtained. A custom-developed TPI sequence15
was used with FOV=220mm, matrix size=64, 3D isotropic, TE/TR=5/100ms, flip
angle=90°, averages=1,
frames=4, p=0.4, and TA=10min28sec. The image reconstruction was implemented
offline with custom-developed programs in C++ (MS Visual Studio 2012). A image slice in each subject was selected for OpenPIV to
perform with interrogation window 32x32 pixels and spacing step 8x8 pixels for
the best output. The velocity map was then displayed in MATLAB (R2018a). Mean and standard deviation (SD) of the velocity magnitude were
computed at each frame. RESULTS
The simulated sodium image intensity in Fig. 2c correlated with the true
CSF intensity although the amplitude was not matched well. The frequency of true
CSF variation was also captured by the simulated image intensity but with an
unmatched value: regular heart beats (50-80/min) and normal respiration
(7-11/min)18 were wraparound into 0.02-0.55 Hz (Fig. 2b). Nevertheless,
the simulation clearly suggested that the dynamic sodium MRI can detect whether
CSF is in motion (0.02-1.5 Hz) or at rest (0.0-0.02 Hz). Fig. 3 shows the 3D frame images of the young subject. CSF
bulk flow velocity map at a slice was demonstrated in Fig. 4. For a
dynamic display, two video clips for the subjects (Fig. 5) will be demonstrated at on-site
presentation. The mean magnitude of CSF velocity was found decreasing by 41.4%
(0.1328 vs. 0.0778 mm/s) from the young to older subject. DISCUSSION
The mismatch between simulated
and true frequencies of CSF variation in Fig. 2d was due to the relatively low temporal
resolution (9 sec), which needs to be improved in the future. The
decrease in velocity with aging in Fig. 4c is consistent with expectation. But it
needs to be confirmed with more subjects. Sodium MRI however is not distinguishing
CSF from blood or interstitial fluid in the parenchyma as they have the same
sodium concentration and co-exist in extracellular space19,20.CONCLUSION
Dynamic
sodium MRI has been demonstrated for the first time the feasibility to map
velocity of CSF bulk flow in tissues in whole brain. This will encourage more
efforts to invest in the improvement of temporal resolution and velocity measurement
accuracy in the future.Acknowledgements
This work was financially
supported in part by NIH grants R56 AG060822, R01 NS113517, and R01 CA111996.
This work was also performed under the rubric of the Center for Advanced
Imaging Innovation and Research (CAI2R, www.cai2r.net), an NIBIB Biomedical
Technology Resource Center (NIH P41 EB017183).References
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