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-MRV³, though these works focused on extremity vasculature. The subjects here have previously been presented as an US and 4D flow MRI⁴ (PC-VIPR⁵) 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). 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 protocol². 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.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.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.