Afis Ajala1, Isabelle Heukensfeldt Jansen1, Seung-Kyun Lee1, Nastaren Abad1, Thomas KF Foo1, J Kevin DeMarco2,3, Robert Y Shih2,3, Gail Kohls3, H Doug Morris2, Angeliki Pollatou2, Haymanot Yalewayker2, Maureen N Hood2,3, Sonja Skeete2,3, Elizabeth Metzger2,3, Vincent B Ho2,3, J Kent Werner2, and Luca Marinelli1
1GE HealthCare, Niskayuna, NY, United States, 2Uniformed Services University of the Health Sciences, Bethesda, MD, United States, 3Walter Reed National Military Medical Center, Bethesda, MD, United States
Synopsis
Keywords: Neurofluids, Neurofluids
Motivation: The impact of respiration on fluid flow in brain parenchyma is poorly understood and remains an on-going research topic in MRI velocimetry.
Goal(s): To analyze the sensitivity of the simultaneous coherent and incoherent motion imaging (SCIMI) method to respiratory-induced phase in the brain parenchyma and to regress this phase contribution from the underlying slow-flow-induced phase.
Approach: Prospectively cardiac-gated SCIMI acquisitions were obtained during three different breathing schemes.
Results: Existence of strong correlations (p<0.005) between the breathing profiles and measured phase in various brain regions indicated the presence of respiration-induced phase in the SCIMI acquisition, and regression of such phases showed promising results.
Impact: This study showed the sensitivity
of simultaneous coherent and incoherent motion imaging method to respiration-induced
phase in the brain, and an initial attempt to regress such phase accrual from the
desired brain slow flows$$$–$$$an important biomarker of glymphatic function.
Introduction
The removal of metabolic waste (produced
by awake or active brain) occurs mostly during sleep and a disruption of
this restorative slow-flow process can negatively affect neural functions1. Slow flow in the brain -
cerebrospinal fluid (CSF), cisterns and subarachnoid spaces - has been shown to
be partly driven by respiration2,3. Breathing-related susceptibility
changes can also indirectly influence the signal phase in echo planar imaging
(EPI)4,5. However, the dynamics of respiration-induced
flow in the brain remains poorly understood. Chen, et al. attempted to use simultaneous
multi-slice EPI phase contrast imaging to study the dynamics of
respiratory-induced flow in the brain as routine cine-phase contrast techniques
of flow imaging inherently cannot detect respiratory-related velocity changes as each image has randomized
respiratory phase contributions due to sorting within the cardiac cycle6. Recent
interest to simultaneously understand the waste removal processes and the
microstructures of the gray/white matter has led to the customization of the
well-known Stejskal-Tanner diffusion imaging method for simultaneous coherent
and incoherent motion imaging (SCIMI) of slow flow in the brain parenchyma
using the magnitude and phase information respectively7. Here, we analyze the sensitivity
of SCIMI to respiration-induced phase in the brain parenchyma and
show an initial attempt to regress such induced phase to obtain a more accurate
slow flow measurement$$$-$$$an important biomarker of glymphatic function. Materials and Methods
All images were acquired on an MRI
scanner equipped with a high-performance gradient system (MAGNUS$$$-$$$GE HealthCare,
Waukesha, WI, USA) that can simultaneously deliver a maximum gradient strength
(Gmax) and slew rate (SRmax) of 300 mT/m and 750 T/m/s
respectively8. RF signal transmission and
reception was achieved using an integrated 16-rung birdcage body coil and a
32-channel receiver coil (NOVA Medical Inc. Wilmington, MA, USA) respectively. A
SCIMI pulse sequence was designed with a b=2000 s/mm2 and velocity
encoding (VENC)=300 um/s (Figure 1). Prospectively cardiac-gated acquisitions
were obtained during three breathing schemes (free, hold and slow breath) that
were monitored with respiratory bellows. Cardiac pulsation was monitored with a
peripheral pulse oximeter plethysmograph. A single q-space encoding vector was
measured per R-R interval at peak systole. SCIMI acquisitions were separately carried
out in the x (qx) and z (qz) gradient directions, and
only 30 q-space vectors were acquired to limit the total scan duration to ~30 s
due to breath-hold constraint. For a constant eddy current in each q-space acquisition,
each q-vector had identical gradient waveform, and an additional zero-diffusion-weighted
reference was acquired. Three volunteers able to hold their breath for
30 s were imaged using SCIMI upon receiving a written informed
consent. For each volunteer, 3 axial slices were positioned on the corpus
callosum with FOV=24 cm, voxel=2x2x2 mm3 and TE=70.2 ms.
SCIMI Reconstruction and Analyses:
All acquisitions were reconstructed
in MATLAB (MathWorks, Natick, MA, USA) using Orchestra software development kit
(GE HealthCare, Waukesha, WI, USA). The phase image of each q-vector
acquisition was unwrapped and four parcels in the anterior, posterior, right
and left side of the brain were semi-automatically drawn on the first slice.
Cross-correlation of the mean phase in each parcel and the respiratory profiles
was estimated. Further, a pixel-wise correlation at zero time-lag between the
respiratory profile and the phase images was calculated. Lastly, respiration-induced
phase was isolated using a generalized linear regression model (GLM) defined
as:
$$y=\beta_0+\beta_1x_1+\beta_2x_2 \tag{1}$$
where $$$y=$$$measured
phase, $$$x_1=$$$respiratory signal and $$$x_2=$$$third order polynomial.Results and Discussion
Representative respiratory profiles from a single volunteer show the
three breathing profiles and the corresponding acquisition time points (Figure
2). Sample magnitude and phase images for a single q-vector at a single time
point are shown in Figure 3. The temporal evolution of the mean phase
extracted from the parcels alongside the z-scored respiratory bellow signal are
shown for the x and z acquisitions and for all three breathing profiles (Figures 3C-3H). The measured phase has a marked fundamental frequency periodicity equal
to that of the respiratory signal as displayed in the cross-correlation analyses
plots (Figures 4A-4F). The maximum correlation occurred at zero time-lag
for most parcels and breathing schemes. The pixel-wise correlation between the
measured phase and the respiratory signal unveiled the spatial distribution of
the respiration-induced phase (Figures 4G-4L). Comparatively, a flatter distribution is
observed for the breath-hold acquisitions that may
indicate a lesser dependence of the measured phase on respiration. The
GLM-extracted respiration-induced phase retained the periodicity of the
respiratory profile but the residual phase did not (Figure 5).Conclusion
The SCIMI pulse sequence is
sensitive to respiration-induced phase, and regression of such phase accruals using
GLM promises a more accurate slow-flow measurement in the brain$$$-$$$a result that
needs further verification.Acknowledgements
Research reported in this work was supported by the CDMRP under award number: W81XWH-22-2-0038. The opinions and assertions expressed herein are those of the authors and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, or the Department of Defense.
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