Preclinical 4D-flow magnetic resonance phase contrast imaging of the murine aortic arch

<div><p>Purpose</p><p>Cardiovascular diseases remain the number one death cause worldwide. Preclinical 4D flow phase contrast magnetic resonance imaging can provide substantial insights in the analysis of aortic pathophysiologies in various animal models. These insights may allow a better understanding of pathophysiologies, therapy monitoring, and can possibly be translated to humans. This study provides a framework to acquire the velocity field within the aortic arch. It analyses important flow values at different locations within the aortic arch. Imaging parameters with high temporal and spatial resolution are provided, that still allow combining this time-consuming method with other necessary imaging-protocols.</p><p>Methods</p><p>A new setup was established where a prospectively gated 4D phase contrast sequence is combined with a highly sensitive cryogenic coil on a preclinical magnetic resonance scanner. The sequence was redesigned to maintain a close to steady state condition of the longitudinal magnetization and hence to overcome steady state artifacts. Imaging parameters were optimized to provide high spatial and temporal resolution. Pathline visualizations were generated from the acquired velocity data in order to display complex flow patterns.</p><p>Results</p><p>Our setup allows data acquisition with at least two times the rate than that of previous publications based on Cartesian encoding, at an improved image quality. The “steady state” sequence reduces observed artifacts and provides uniform image intensity over the heart cycle. This made possible quantification of blood speed and wall shear stress (WSS) within the aorta and its branches. The highest velocities were observed in the ascending aorta with 137.5 ± 8 cm/s. Peak velocity values in the Brachiocephalic trunk were 57 ± 12 cm/s. Quantification showed that the peak flow occurs around 20 ms post R-wave in the ascending aorta. The highest mean axial wall shear stress was observed in the analysis plane between the left common carotid artery (LCCA) and the left subclavian artery. A stable image quality allows visualizing complex flow patterns by means of streamlines and for the first time, to the best of our knowledge, pathline visualizations from 4D flow MRI in mice.</p><p>Conclusion</p><p>The described setup allows analyzing pathophysiologies in mouse models of cardiovascular diseases in the aorta and its branches with better image quality and higher spatial and temporal resolution than previous Cartesian publications. Pathlines provide an advanced analysis of complex flow patterns in the murine aorta. An imaging protocol is provided that offers the possibility to acquire the aortic arch at sufficiently high resolution in less than one hour. This allows the combination of the flow assessment with other multifunctional imaging protocols.</p></div

Mean axial wall shear stress over the cardiac cycle.

<p>Mean axial wall shear stress over the cardiac cycle for four evaluation planes placed at specified locations is shown on the right. The highest wall shear stress can be observed in the third plane. The curves show the mean value of all subjects and their standard error of the mean as error bars. The lowest mean axial wall shear stress occurs in the ascending aorta.</p

Pathline visualization of the blood flow in the aorta during systole.

<p>a) Pathline visualization during systole generated in early systole from two emitter planes perpendicular to the vessel. The emitted pathlines continue into the brachiocephalic trunk, left common carotid artery and the left subclavian artery. The pathlines are masked by a speed-sum-of-squares isosurface. A pathline animation over the cardiac cycle is shown in the supplementary animation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187596#pone.0187596.s004" target="_blank">S3 Fig</a>. b) Visualization of the used emitter planes for the pathlines in the aortic arch. c) Unmasked pathlines are shown that leave the isosurface. The isosurface is shown opaque to easily identify aberrant pathlines.</p

Streamline representation of the blood velocities during systole.

<p>a) Streamline representation of the velocities of one mouse during peak systole. Streamlines are generated from four emitter planes placed perpendicular to the aorta as shown in (c). Streamlines are color coded with the magnitude of the velocity as displayed in the color bar. The isosurface in this image was calculated as speed-sum-of-squares isosurface from the velocity data. One can identify regions of high velocities and low velocities. The vessel lumen is equally filled. Streamlines continue even in the small branches of the aorta. Velocities are lower in the aortic branches than in the aortic root. Supplementary animation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187596#pone.0187596.s003" target="_blank">S2 Fig</a> provides extended streamline visualization from multiple viewing angles. b) Streamline representation of the velocities of one mouse during peak systole from Bovenkamp et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187596#pone.0187596.ref005" target="_blank">5</a>] figure 6 (clipped). <i>“Blood flow visualization with vector magnitude-encoded streamlines in the cardiovascular system of a mouse at 13</i>.<i>76 ms after R wave of the ECG”</i>. c)Visualization of the used emitter planes for the streamlines in the aortic arch. d)Unmasked streamlines are shown that leave the isosurface. The isosurface is shown opaque in order to easily identify aberrant streamlines. e)Placement of the ROIs for SNR analysis.</p

Protocol parameters used for the acquisitions.

<p>Protocol parameters used for the acquisitions.</p

Mean flow over the cardiac cycle.

<p>Flow over the cardiac cycle for four evaluation planes placed at specified locations is shown on the right. Flow is highest in the ascending aorta (AAo). The curves show the mean value of all subjects and their standard error of the mean as error bars. One can observe a trend towards lower flow velocities (plane 1 towards plane 4) as expected and longer time to peak flow durations.</p