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. 2017 Apr;37(4):1483-1493.
doi: 10.1177/0271678X16657345. Epub 2016 Jan 1.

Four-dimensional Flow Magnetic Resonance Imaging and Ultrasound Assessment of Cerebrospinal Venous Flow in Multiple Sclerosis Patients and Controls

Free PMC article

Four-dimensional Flow Magnetic Resonance Imaging and Ultrasound Assessment of Cerebrospinal Venous Flow in Multiple Sclerosis Patients and Controls

Eric M Schrauben et al. J Cereb Blood Flow Metab. .
Free PMC article


A possibly causal relationship between multiple sclerosis and chronic cerebrospinal venous insufficiency has recently been hypothesized. Studies investigating chronic cerebrospinal venous insufficiency have reported conflicting results and few have employed multiple diagnostic imaging modalities across a large patient and control population. In this study, three complementary imaging modalities were used to investigate the chronic cerebrospinal venous insufficiency hypothesis in patients with multiple sclerosis and two age- and sex-matched control groups: healthy volunteers and patients with other neurological diseases. Strictly blinded Doppler ultrasound according to the original chronic cerebrospinal venous insufficiency hypothesis; four-dimensional flow magnetic resonance imaging of venous flow in the head, neck, and chest; and contrast-enhanced magnetic resonance venography for neck and chest venous luminography were acquired. An internal jugular vein stenosis evaluation was also performed across modalities. Percentage of subjects meeting ultrasound-based chronic cerebrospinal venous insufficiency criteria was small and similar between groups. In group-wise and pairwise testing, no four-dimensional flow magnetic resonance imaging variables were statistically significantly different, for any measurement location. In contrast-enhanced magnetic resonance venography of the internal jugular and azygos veins, no statistically significant differences were observed in stenosis scores between groups. These results represent compelling evidence against the chronic cerebrospinal venous insufficiency hypothesis in multiple sclerosis.

Keywords: Doppler ultrasound; four-dimensional flow magnetic resonance imaging; multiple sclerosis; venous blood flow; venous luminography.


Figure 1.
Figure 1.
All images shown in 36 y/o female with migraine. Planes mark PC-VIPR measurement locations. (a) Velocity streamlines in the head from PC-VIPR angiogram. (b) Limited maximum intensity projection (MIP) of CE-MRV of neck veins (left) and PC-VIPR streamlines (right). Areas of stenosis viewed on the CE-MRV MIP (IJV morphology scores < 3) are complemented by PC-VIPR information: slow flow (open arrow) and velocity jet (closed arrow). (c) Limited CE-MRV MIP (left) and corresponding PC-VIPR angiogram and streamlines (right) in the azygos vein. CE-MRV: contrast-enhanced MR venography; IJV: internal jugular vein; PC-VIPR: phase contrast vastly undersampled isotropic projection reconstruction.
Figure 2.
Figure 2.
Group-wise comparisons of average ( ± standard deviation) total flow (in ml/cycle, top) and percent retrograde flow (%RF) over the cardiac cycle (bottom) for all measured locations. No statistically significant differences were found at any location between any of the three groups. %RF: percent retrograde flow.
Figure 3.
Figure 3.
(a) Group-wise comparisons of detected narrowing, shown as percentage of total subjects for measured cases in the right and left IJV. (b) Reader (and US) comparisons of detected IJV narrowing, shown as a percentage of total subjects. From the same CE-MRV data, reader 2 appears to detect narrowing more frequently. Prevalence is higher in the left IJV than right IJV. CE-MRV: contrast-enhanced MR venography; IJV: internal jugular vein.

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