4D Flow MRI for assessing cerebral venous flow, a potential surrogate marker for capillary pulsatility in Alzheimer’s disease
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

[1] Roher AE. Editorial Comment: Cardiovascular system participation in Alzheimer's disease pathogenesis. Journal of Internal Medicine. 2015; 277(4): 426-28.

[2] Bateman GA, Levi CR, Schofield P, Wang Y and Lovett EC. The venous manifestations of pulse wave encephalopathy: windkessel dysfunction in normal aging and senile dementia. Neuroradiology 2008; 50:491-497.

[3] Gu T, Korosec FR, Block WF, Fain SB, Turk Q, Lum D, et al. PC VIPR: a high-speed 3D phase-contrast method for flow quantification and high resolution angiography. AJNR Am J Neuroradiology 2005;26(4):743–749.

[4] Liu J, Redmond MJ, Brodsky EK, Alexander AL, Lu A, Thornton FJ, et al. Generation and visualization of four dimensional MR angiography data using an undersampled 3-D projection trajectory. IEEE Trans Med Imaging. 2006; 25(2):148–157.

[5] Schrauben E, Wåhlin A, Ambarki K, Spaak E, Malm J, Wieben O, et al. “Fast 4D flow MRI intracranial segmentation and quantification in tortuous arteries.” J Magn Reson Imaging. 2015 Nov;42(5):1458-64.

Figures

Figure 1. The segmented 3D vessels with centerline points for the a.) Superior sagittal sinus (SSS), b.) Straight sinus (STS) and c.) Transverse sinus (TS) extracted from the PCVIPR data. d.) PI and e.) MBF(mL/s) throughout the venous segments shown as color maps for one control and one AD subject.

Figure 2. Pulsatility index values for 50 subjects including AD (n = 25) and controls (n=25) in the Superior sagittal sinus (SSS), Straight sinus (STS) and Transverse sinus (TS).

Figure 3. Pulsatility index for 50 subjects including AD (n = 25) and controls (n =25). For each vessel segment the pulsatility index statistically increased in the AD group.

Figure 4. Mean blood flow (mL/s) values for 50 subjects including AD (n =25) and controls (n = 25) in the Superior sagittal sinus (SSS), Straight sinus (STS) and Transverse sinus (TS).

Figure 5. Mean blood flow (mL/s) for 50 subjects including AD (n = 25) and controls (n =25). For each vessel segment the mean flow statistically decreased in the AD group except in the STS segment.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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