Jacob Jan Sloots1, Ayodeji L. Adams1, Peter R. Luijten1, Geert Jan Biessels2, and Jaco J. M. Zwanenburg1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 2Neurology, University Medical Center Utrecht, Utrecht, Netherlands
Synopsis
The cardiac cycle and respiration both influence CSF
dynamics and therefore the displacement of brain tissue. In this work we
unravel their contribution to brain tissue displacement using a single shot 2D cine
displacement-encoded imaging method employing stimulated echoes (DENSE) for
brain motion measurements. Displacement-encoded data sets in the Feet-to-Head
direction of seven volunteers were fitted to a linear model. Consistent trends in
displacements were observed. The developed DENSE sequence results showed
similar sized contributions to brain tissue displacement. Relating these displacements to contributions to the
clearance system remains future work.
Introduction
Brain
tissue motion induced by the cardiac and respiration cycles is considered to be
involved in the drainage of cerebral waste1. Although
cardiac and respiratory pulsations were claimed to play different roles2, this
was based on T2* weighted measurement which reflect both blood flow and tissue
motion together. We aim to unravel the influence of cardiac and respiratory
contributions by specifically measuring the displacement of brain tissue with a
single shot 2D DENSE acquisition and fitting a linear model to the observed
data. Method
A cardiac
triggered, single shot TFEPI 2D cine-DENSE sequence3 was designed to measure heart beat and respiration related brain tissue motion
(Figure 1). The displacement sensitivity was set to $$$D_{enc}$$$=0.35 mm/$$$\pi$$$ in the
Feet-to-Head direction (resolution 2.98x3.11x3mm3 and FOV 250x250mm2,
TFE factor 3, EPI factor 15, SENSE 1.8 (AP direction), TE/2 9ms, and three
frames at respectively 0, 23 and 46% of the average cardiac cycle). A variable excitation flip angle $$$\alpha_{n}$$$ over the cardiac cycle was recursively calculated4 using a T1 value of 1100ms and a maximum flip angle
of 30˚.
Written
informed consent was obtained from all volunteers in accordance with the
Ethical Review Board of our institution. Seven healthy subjects (3 females, age
25 ± 3 years) were included and scanned at 7T (Philips Healthcare, Best, The
Netherlands) using a 32 channel head coil. The 2D cine-DENSE measurements were
repeated over 200 dynamics with alternating encoding direction, resulting in
600 snapshots over time, and a scan duration of 5-10 min (80-40bpm). Slice planning is shown in Figure 2. Physiological
data was recorded during scanning using a vector cardiogram (VCG) for
triggering and a respiration belt to trace abdominal breathing (Figure 3).Analysis
The
measured apparent displacement $$$d$$$ of
brain tissue at cardiac phase $$$c$$$ and
respiration position $$$r$$$, was assumed
to be a linear independent combination of cardiac and respiratory displacement
contributions represented by $$$d_{c,i}$$$ and $$$d_{r,delta}$$$ respectively.
The static phase errors and respiratory induced $$$B_{0}$$$ offsets were described by $$$d_{0}$$$ and $$$d_{r,off}$$$, respectively, yielding the model
$$d(c,r) = \sum_{i=1}^{3} x_{c,i} d_{c,i}+x_{r,delta} d_{r,delta}+x_{r.meas}+d_{r,off}+d_{0}$$
Weighting factors $$$x$$$ were deduced from the physiological data, after smoothing the respiration signal by Fourier filtering between 0.1 and 1 Hz. Depending on the alternating encoding polarity, $$$x_{c,i}$$$ had alternating signs for odd or even dynamic $$$n$$$. For $$$i$$$ is 1, 2 or 3, $$$x_{c,i}=(-1)^{n}$$$ if a frame was acquired at respectively 0, 23 or 46% of the associated actual cardiac interval. Cardiac weighting factors were linearly redistributed for frames that fell between these intervals, such that
$$ 0 \leq \parallel x_{c,i} \parallel \leq 1$$
$$ \sum_{i=1}^{3} \parallel x_{c,i} \parallel = 1 $$
The respiration trace was described in the model by coefficients $$$x_{r,delta}=(-1)^{n} \Delta r$$$ and $$$x_{r,meas} = \Delta r$$$, where $$$\Delta r$$$ is the difference in abdominal respiration position between encoding and decoding. The complete linear model was solved voxelwise by linear regression, using an additional weighting factor proportional to $$$SNR_{\phi} \propto (DENSE_{MAG})^2$$$, where $$$DENSE_{MAG}$$$ is the magnitude of the DENSE image. Wrong triggers were detected and related images were retrospectively discarded for the analysis.
Results and Discussion
Imaging was
successful in all subjects, and triggering was consistent; on average 151
dynamics (range 106 to 199) could be used for analysis. Consistent displacement
maps per subject were obtained (Figure 4). Regional analysis was performed in
three regions of interest (see Figure 4a for regions) for both cardiac and respiratory motion. Cardiac related displacement was largest
in the deep brain (basal ganglia) and was on average -99±30µm and -139±17µm at
23% and 46% of the cardiac cycle, respectively. The results (Figure 5) show
that contributions from heart and respiration are in the same order of
magnitude. A rotation was observed for the respiratory displacement, where the
back of the head moves in the Head
direction whereas the front of the head moves in the Feet direction during inspiration and vice versa during expiration. $$$B_{0}$$$ offset fluctuations related to respiration decreased from the
base of the brain to the top of the brain, and ranged typically between 0 and 10
Hz, which compares well to the literature5. We did not
assess the feasibility of measuring low frequency fluctuations2 (below 0.1 Hz).Conclusion
The developed
single shot 2D DENSE sequence is capable of consistently unraveling cardiac and respiratory related
brain motion, taking into account offsets due to static phase errors and $$$B_{0}$$$ fluctuations. This method may be useful for MR elastography
with intrinsic activation6 and provide
insight in the sources of pulsatile brain motion. Relating this motion to
contributions to the clearance system remains future work.Acknowledgements
The research leading to
these results has received funding from the European Research Council under the
European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant
agreement n°337333.References
1. Mestre H, Kostrikov R, Nedergaard M, et al. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clinical Science. 2017;131(17):2257‐2274.
2. Kiviniemi V, Wang X, Nedergaard M, et al. Ultra-fast magnetic resonance encephalography of physiological brain activity – Glymphatic pulsation mechanisms? Journal of Cerebral Blood Flow & Metabolism. 2016;36(6):1033‐1045.
3. Soellinger M, Rutz M, Boesiger P, et al. 3D cine displacement-encoded MRI of pulsatile brain motion. Magnetic Resonance in Medicine. 2009;61(1):153‐162.
4. Fischer S, McKinnon G, Boesiger P, et al. Improved myocardial tagging contrast. Magnetic Resonance in Medicine. 1993;30(2):191‐200.
5. Van Gelderen P, De Zwart J, Duyn J, et al. Real-time shimming to compensate for respiration-induced B0 fluctuations. Magnetic Resonance in Medicine. 2007;57(2):362‐368.
6. Weaver J, Pattison A, Paulsen K, et al. Brain mechanical property measurement using MRE with intrinsic activation. Physics in Medicine and Biology. 2012;57(22):7275‐7287.