Eric Schrauben1, Sarah Kohn2, Samuel Frost2, Oliver Wieben2,3, and Aaron Field2
1Centre for Advanced MRI, University of Auckland, Auckland, New Zealand, 2Radiology, University of Wisconsin - Madison, Madison, WI, United States, 3Medical Physics, University of Wisconsin - Madison, Madison, WI, United States
Synopsis
Contrast-enhanced
MR venography scoring in internal jugular veins is performed and compared with 4D flow MRI and ultrasound
assessment in patients with multiple sclerosis, patients with other
neurological disorders and healthy controls. Narrowing assessment is shown to be
more variable in flow MRI and ultrasound.Purpose
The Chronic Cerebrospinal Venous
Insufficiency (CCSVI)
1 hypothesis posits that impeded venous
drainage may cause or exacerbate multiple sclerosis (MS). One of the main
criteria proposed for CCSVI lies in determining internal jugular vein (IJV)
stenosis using B-mode ultrasound (US)
2. Venous caliber assessment can
be challenging, especially in IJVs which may take different shapes when viewed axially
(e.g. pinpoint, crescentic, flattened, oblong). Additionally, unlike arterial
stenotic blood flow jets, a collapsing venous stenosis may produce slow flow or
even reflux. 2D projections produced from US of IJVs may lead to over- or
underestimation of cross-sectional area, depending on vessel shape and
transducer direction. Compared with US, contrast enhanced-MR venography (CE-MRV)
has distinct benefits: it is less operator-dependent
with repeatable protocols, entire vessels can be assessed non-invasively, and
bias from interaction between subjects and unblinded operators is avoided.
Studies have compared US
and CE-MRV
3, though these works focused on extremity vasculature. The
subjects here have previously been presented as an US and 4D flow MRI
4
(PC-VIPR
5)
comparison.
The purpose of this study was to add CE-MRV IJV
caliber scoring to compare with PC-VIPR and US assessment in the context of the CCSVI
hypothesis. These data were gathered and assessed in blinded fashion in
patients with MS (all subtypes), with other neurological disorders (OND) and
healthy controls (HC).
Methods
Demographics: The study
population consisted of 74 MS patients (Age: 46 ± 11 yrs, 47F), 47 HCs (Age: 46
± 11 yrs, 26F), and 42 ONDs (Age: 49 ± 13 yrs, 28F).
MR Acquisition: CE-MRV of the neck was performed at 3T (Discovery MR750, GE Healthcare): FOV (covering aortic
root to confluens sinuum) = 28x28x26 cm, resolution = 0.55x0.55x0.80 mm,
TE/TR/α = 3.4ms/1.3ms/28 with a single injection of gadofosveset trisodium
(Ablavar, Lantheus Medical Imaging)
at a dose of 0.03–0.05 mmol/kg and rate of 3 mL/s. PC-VIPR in the neck (same
location as CE-MRV) was also performed: (TE/TR/α = 3.0ms/7.9ms/15°, resolution
= 0.86 mm isotropic, Venc = 40-70 cm/s). Cardiac triggers were
recorded for retrospective cardiac gating.
MR Analysis: For semiquantitative assessment of venous caliber, CE-MRVs were scored by two
radiologists blinded to subject identity, date/sequence of scan, images
depicting the brain or spinal cord, and each other’s scores. The scoring followed
the scale from Zivadinov et al.
6 – IJV cross-sectional morphology at
narrowest point (1-absent; 2-pinpoint; 3-flattened; 4-crescentic; 5-ellipsoidal/round),
and IJV image quality (1-poor; 2-acceptable;
3-good; 4-excellent). Flow processing was completed by one person uninvolved with image
acquisition and blinded to subject status and brain/cord images. IJV percent
retrograde flow (%RF) was measured from a single PC-VIPR scan at three locations
(upper, mid, lower).
Ultrasound: A
certified ultrasonographer trained in the Zamboni CCSVI analysis and blinded to
the subject’s diagnosis assessed stenosis of the IJVs using B-mode US. This was
performed consistent with the Zamboni protocol
2.
Statistics: Group CE-MRV
scoring differences were assessed on a per-vessel basis using a Wilcoxon
sum-rank test. Cohen’s κ with linear weights was used to assess inter-rater
reliability (all 5 scores and dichotomized scoring, vessel score < 3 or ≥ 3).
A binary IJV narrowing determination was made for each method of assessment: CE-MRV
(vessel score < 3), PC-VIPR (any measurement plane with %RF > 5%), and ‘B-mode
US evidence of proximal IJV stenosis’
2. Resulting percentage of total
subjects exhibiting narrowing was compared between readers, groups, and
modalities.
Results
Figure
1 demonstrates CE-MRV coronal maximum intensity projections (MIPs) and a
corresponding PC-VIPR visualization. Locations of diminished caliber can be
distinguished (arrows) and are denoted by low IJV morphology scores. Acceptable
to good IJV image quality scores (all subjects averaged: reader 1 = 2.8±0.5, reader 2 = 3.3±0.7) and
moderate inter-rater reliability were observed (κ = 0.56). For dichotomized
scoring, inter-rater reliability increased (κ = 0.60). No statistically
significant differences between any group combinations were observed for CE-MRV
morphology measurements, for either reader. Figures 2 and 3 demonstrate percent
of total subjects exhibiting IJV narrowing across groups and readers (as well
as flow and US results). Higher occurrence of narrowing is evident in the left
IJV, and greater variability is seen for both PC-VIPR and US compared with
CE-MRV.
Conclusion
CE-MRV
appears to be a more robust determinant of IJV narrowing, as other narrowing
assessments suffer from potential user-dependence (B-mode US) and flow voids from
excessively slow blood flow (flow MRI). This study presents IJV narrowing
assessment from three independent and complimentary imaging techniques, each with
their own strengths and weaknesses. These negative results do not support a
relationship between detection of IJV stenosis and MS and fail to support the
CCSVI hypothesis.
Acknowledgements
We
gratefully acknowledge funding from National MS Society grant #RC1003-A-1, and
GE Healthcare for their research support.References
1. Zamboni et al. Phlebology 2010. 2. Zamboni et al. J Neurol
Sci 2009. 3. Hussey et al. Eur J Vasc Endovasc 2012. 4. Schrauben et al. MRA Club 2015. 5. Johnson
et al. JMRI 2008 6. Zivadinov
et al. Neurol 2011.