Leonardo A Rivera-Rivera1, Tilman Schubert2, Kevin M Johnson1, Sterling C Johnson3, Patrick Turski2, and Oliver Wieben1,2
1Medical Physics, University of Wisconsin Madison, Madison, WI, United States, 2Radiology, University of Wisconsin Madison, Madison, WI, United States, 3Medicine, University of Wisconsin Madison, Madison, WI, United States
Synopsis
Cerebral arteries are
often morphologically altered and dysfunctional in Alzheimer’s disease. In this
study, 4D flow MRI was used to assess cerebral venous flow, particularly mean blood
flow and pulsatility index in patients with AD, and in healthy age matched controls.
We found a statistically significant increase in pulsatility index and decrease
in mean flow for the AD in most venous segments. With the large volume coverage
and high temporal and spatial resolution, 4D flow MRI can provide additional
biomarkers of vascular health that can contribute to the identifying patients
who could benefit from interventions to improve circulatory system functions.Purpose
Alzheimer’s
disease (AD) is the most common type of dementia in the elderly population.
Although the leading pathological finding in AD is amyloid deposition in the
brain, there is evidence that alterations of the cerebrovascular system might
play a role in the development of the disease [1]. It has been shown that
arterial pulsatility is increased in AD [1]; however, less information is
available about changes in venous flow and venous pulsatility in individuals
with AD [2]. Recent advances in MR hardware, data acquisition, and
reconstruction have facilitated the use of 4D flow MRI in clinically feasible
scan times. This approach enables both volumetric angiographic and quantitative
assessment of blood flow velocities in a single acquisition. With adequate
spatial and temporal resolution, 4D flow MRI seems ideally suited for
comprehensive cranial hemodynamic assessment. The purpose of this study was to compare
venous flow volume and pulsatility in an AD cohort and age matched controls. Using
ECG-gated 4D flow MRI we test the hypothesis that AD related increased
intracranial arterial pulsatility is transmitted through the arterioles and
capillaries and that the venous system has also increased pulsatility. PI
of the venous outflow may be a surrogate marker to the microvasculature that
cannot be assessed with the current limits of spatial resolution.
Methods
Subjects: The study population consisted of 25 AD
patients (age range 57-89y, mean=71y, 11 F), and 25 older control adults (age
range 66-85y, mean= 73y, 12 F). MRI: Volumetric, time-resolved phase contrast (PC) MRI data with
3-directional velocity encoding were acquired on a 3T clinical MRI system
(MR750, GE Healthcare) with an 8 channel head
coil (Excite HD Brain Coil, GE Healthcare), with a 3D radially
undersampled sequence, PC VIPR [3] with the following imaging parameters Venc =
80 cm/s, imaging volume = 22x22x10 cm3, (0.7 mm)3
acquired isotropic spatial resolution, TR/TE=7.4/2.7ms, scan time ~ 7 min, retrospective cardiac
gated into 20 cardiac phases with temporal interpolation of high spatial
frequency k-space data [4]. Flow analysis: Automatic vessel
segmentation and flow quantification was performed in a customized Matlab tool
[5] (Mathworks, Natick, MA) from time maximum intensity projection (tMIP)
dynamic PC MRAs reconstructed from the 4D flow data. The complete vascular tree
was extracted using a centerline process, recording coordinates and labels for every
branch. A centerline guided flow tracking algorithm was used to visualize and
select the venous segments for further analysis. Flow rates were calculated for
every selected branch by averaging flow data obtained in local cross-sectional
cut-planes automatically placed in every centerline point perpendicular to the
axial direction of the vessel. For this purpose 4 venous segments were selected
(Fig. 1) (a, b, c): posteroinferior portion of the Superior Sagittal Sinus
(SSS), middle segment of the Straight Sinus (STS), and the Transverse Sinus
(TS)(left and right) segment just before the Sigmoid Sinus. Pulsatility index ($$$PI=\frac{Q_{max}-Q_{min}}{Q_{mean}}$$$) and mean
blood flow were calculated and groups were compared with Student’s t-test
(significance for p<0.05).
Results
Results
for the vessel analysis are summarized in Figures 2-5. An increased PI in the
AD group was found for all segments when compared with controls, with
significant differences in all segments. The AD group also showed a decrease in
blood flow for all the segments when compared with controls, with significant
differences in all segments except in the STS segment.
Discussion
These
results on the venous system resemble recent findings on the arterial system:
AD patients have reduced blood flow and increased PI compared to age matched
normal subjects. The significantly increased pulsatility in all segments in the
AD cohort may reflect the primary cortical pathology of AD, and the associated
arterial, arteriolar and capillary pulsatility alterations. These results are contrary
to patients with vascular dementia, where a normal SSS pulsatility was reported
[2]. A simple propagation from increased arterial pulsatility to the cortical
veins and subsequently to the SSS in AD is less probable, as this should also
be present in patients with vascular dementia.
Conclusions
This
study demonstrates the feasibility
of hemodynamic analysis over a large vascular territory in the context of
Alzheimer’s disease with 4D flow MRI within a 7-minute acquisition. Hemodynamic
characteristics of the venous vascularity on AD group were investigated and
compared to controls and significantly
increased pulsatility was found in all
segments of the AD cohort. With the large volume coverage and high temporal and
spatial resolution demonstrated here, 4D flow MRI can provide additional
biomarkers of vascular health that can contribute to identifying patients who
could benefit from interventions to improve circulatory system functions.
Acknowledgements
We
gratefully acknowledge funding by the NIH (NIA P50-AG033514 and NIGMS R25GM083252) as well as GE Healthcare
for their assistance and support. The content is
solely the responsibility of the authors and does not necessarily represent the
official views of the NIH.References
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