Yining He1, Jianing Tang1,2, Tianrui Zhao1,2, and Lirong Yan1,3
1Radiology, Northwestern University, Chicago, IL, United States, 2Biomedical Engineering, Northwestern University, Evanston, IL, United States, 3Neurology, University of Southern California, Los Angeles, CA, United States
Synopsis
Keywords: Blood vessels, Aging
Arterial
stiffness is an important risk marker for poor brain aging, vascular disease,
and dementia. Greater arterial stiffness leads to the transmission of excessive
pulsations from the greater vessels into the downstream capillary and tissue
causing microvascular dysfunction. However, previous studies have mainly focused
on central or peripheral pulse wave velocity assessment. The present study has demonstrated
a significant association of the PWV of the feeding arteries to the brain and
its downstream territorial perfusion assessed by using two new MRI techniques,
which could provide valuable insight into the neurovascular pathology of aging
and brain dysfunction.
Introduction
A growing body
of research indicates that arterial stiffness is an important risk marker for poor
brain aging, vascular disease, and dementia1. Greater arterial
stiffness leads to the transmission of excessive pulsations from greater vessels
into the downstream capillary and tissue causing microvascular dysfunction.
Arterial stiffness is commonly assessed by measuring pulse wave velocity (PWV).
However, existing approaches mainly measure the central and/or peripheral PWV2.
The association between the arterial stiffness of feeding arteries in the
brain, such as the internal carotid artery, and downstream cerebral territorial perfusion has not been fully elucidated. A previous study has introduced an oblique-sagittal
phase-contrast MRI (OS PC-MRI) method for directly assessing carotid PWV (cPWV)
between the common carotid artery and internal carotid artery (CCA-ICA)3. The goal of this study is to investigate
the association between carotid arterial stiffness measured using OS PC-MRI and
downstream territorial perfusion generated by random vessel-encoded ASL4 individually in a cohort of elderly adults. Methods
MR Imaging
protocol:
All experiments
were carried out on a Siemens 3T Prisma MRI scanner (Magneton Prisma, Siemens
Healthcare, Erlangen, Germany) using a 20-channel head coil. 25 elderly
participants ( 14 female, 72+-7.38years ) were enrolled in this study after providing informed consent. A quick time-of-flight (TOF) MR angiography
scan was performed to localize carotid arteries including CCA and ICA. ECG
retrospectively gated OS-PC MRI was performed on each subject to cover the most
CCA-ICA segment with the following imaging parameters: resolution=1x1x1mm3,
Venc=80cm/s, TE/TR=4.32/14.22ms, flip angle=10°, real temporal
resolution=14.22ms, number of phases=70-90, scan time is 1 to 2min depending on
the heart rate of each participant. Random VE-ASL data was collected to
generate perfusion territorial maps with the imaging parameters: FOV= 220×220
mm2, matrix size=64×64, TE/TR=22/3500ms, 16 slices with slice thickness of 6mm,
labeling duration=1500ms, post-labeling delay (PLD)=1500ms, 60 pairs of
encoding steps with random orientation, phase and wavelength were acquired with
two additional pairs of global label/control. Multi-delay ASL was also
performed with imaging parameters: FOV=220x220mm2; resolution=96x96;
TE/TR=37/4100ms; 54 slices with slice thickness of 2.5mm; lableing
duration=1500ms, PLDs=500ms/1300ms/1500ms/1800ms/2300ms. Magnetization Prepared
Rapid Gradient Echo (MPRAGE) was acquired for generating the gray matter mask.
Data
analysis:
The velocity
waveform across a cardiac cycle was measured at each axial position along
CCA-ICA. The time-to-feet method was used to calculate the transit time along the
vessel. cPWV was calculated as the inverse slope of the line fitted to the
transit-time versus distance along the vessel. Perfusion territorial mapping
and corresponding feeding arteries (left ICA, right ICA, and vertebral artery)
were generated simultaneously from rVE-ASL data4. Left and right ICA territorial
masks were generated from each subject. CBF and ATT maps were calculated from the
multi-delay ASL data. Mean gray matter CBF and ATT values were extracted from
each subject. Mean ICA territorial CBF (tCBF) and ATT (tATT) values were calculated
from the multi-delay ASL-generated CBF and ATT maps within the ICA territory mask
generated from rVE-ASL from the same side as that of cPWV. Two rVE-ASL data
showed bad quality due to the head motion and artifacts. The perfusion
territories from the two subjects were acquired from the standard VE-ASL
instead.
The correlations between cPWV vs. CBF and ATT were calculated
across subjects using Pearson correlation coefficients. Results
Figures 1 a and
b show the scatter plots of mean gray matter CBF vs. cPWV and mean gray matter
ATT vs. cPWV, respectively. Mean gray matter CBF significantly reduced with elevated
cPWV (r=-0.42; p=0.035),
whereas there were no changes in ATT as cPWV increased (r=-0.04; p=0.83).
Figures 2 a and b show the scatter plots of ipsilateral ICA territorial CBF vs. cPWV and ICA territorial ATT vs. cPWV, respectively. Similar
to the findings from gray matter, there was a significant association between
cPWV and ICA territorial CBF (r=-0.43; p=0.042) whereas no association was
observed between cPWV and territorial ATT (r=0.04; p=0.85). No significance was observed between cPWV vs. the contralateral ICA territorial CBF and ATT. These findings indicate that elevated cPWV was accompanied by the reduction in its downstream directly associated territorial CBF.Discussion & Conclusion
This study is
the first to directly study the relationship between arterial stiffness of the
feeding arteries in the brain and perfusion of its downstream vascular
territory from individuals. This study shows several advantages, compared
to previous research. First, OS PC-MRI was applied to directly access the
arterial stiffness of feeding arteries in the brain, instead of accessing the central
or peripheral arterial stiffness. Second, variations in cerebral vascular
territories have been commonly observed, especially in elderly subjects. In
this work, we extracted the accurate ICA territory from individuals using
rVE-ASL instead of using a vascular atlas. This study provides a direct evidence between carotid arterial stiffness and its downstream carotid
territorial CBF, which could enhance our understanding of the link between
macrovascular and microvascular dysfunction as well as the underlying
neurovascular pathology of aging and cognitive decline. Acknowledgements
This work is supported by grants of NIH R01NS118019, RF1AG072490, and BrightFocus Foundation A20201411S.References
1. Parittotokkaporn S, de Castro D, Lowe A, Pylypchuk R.
Carotid Pulse Wave Analysis: Future Direction of Hemodynamic and Cardiovascular
Risk Assessment. JMA J. 2021;4(2):119-128. doi:10.31662/jmaj.2020-0108
2. Meyer ML, Palta P, Tanaka H, Deal JA, Wright J, Knopman DS, Griswold ME, Mosley TH, Heiss G. Association of central arterial stiffness and pressure pulsatility with mild cognitive impairment and dementia: the Atherosclerosis Risk in Communities Study-Neurocognitive Study (ARIC-NCS). Journal of Alzheimer's Disease. 2017 Jan 1;57(1):195-204.
3. Heidari Pahlavian S, Cen SY, Bi X, Wang DJJ, Chui HC,
Yan L. Assessment of carotid stiffness by measuring carotid pulse wave velocity
using a single-slice oblique-sagittal phase-contrast MRI. Magn Reson Med.
2021;86(1):442-455. doi:10.1002/mrm.28677
4. Wong EC, Guo J. Blind detection of vascular sources
and territories using random vessel encoded arterial spin labeling. Magnetic
Resonance Materials in Physics, Biology and Medicine. 2012 Apr;25(2):95-101.