- Background and Rationale A carotid web (CaW) is a shelf-like, thin, triangular endoluminal projection-typically arising from the posterior wall of the internal carotid artery (ICA) bulb-considered by many to be an intimal variant of fibromuscular dysplasia and associated with embolic ischemic stroke in otherwise low-risk, younger patients. Although CT angiography (CTA) is most frequently used to diagnose CaW, characteristic appearances are detectable on longitudinal B-mode carotid duplex ultrasound (DUS) with supportive Doppler findings; microflow/superb microvascular imaging can improve conspicuity. Population prevalence in the general young adult population is unknown; most estimates come from stroke cohorts (≈2% among symptomatic populations; higher within cryptogenic stroke subsets), so a dedicated, population-based sonographic study is needed.
- Objectives and Hypotheses Primary objective: Estimate the point prevalence of carotid web in a general young adult population aged 15-25 years using duplex sonography.
Secondary objectives:
- Describe CaW laterality and morphology (web thickness, length, and projection angle) on ultrasound.
- Estimate prevalence of concomitant ICA/common carotid artery (CCA) atherosclerotic changes or stenosis.
- Assess inter-observer agreement for CaW detection on DUS.
- In an adjudicated subset, compare DUS-suspected CaW with CTA (optional validation).
Hypothesis: Carotid web is present in 2 % of the general 15-25-year population (two-sided). (This is a planning assumption; true prevalence may be lower/higher. Literature in symptomatic cohorts ranges roughly 2%, higher in cryptogenic stroke; general-population data are lacking.)
- Study Design Cross-sectional, multicenter, population-based sonographic survey with blinded central image adjudication, reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for cross-sectional studies.
- Study Population Setting & sampling frame
- Community-based recruitment (secondary schools/universities).
- Stratified cluster sampling by sex, age bands (15-17, 18-21, 22-25), and recruitment site to approximate the underlying population.
- Sample Size Assumptions
- Expected prevalence p=0.02 (2%)
- Desired absolute precision d=0.01 (±1%)
- Confidence level 95% → Z=1.96 Formula n = Z2 p(1-p)d2 = 1.962×0.02×0.980.012 = 752.95n ;=; \\frac{Z^2, p(1-p)}{d^2} ;=; \\frac{1.96^2 \\times 0.02 \\times 0.98}{0.01^2} ;=; 752.95n=d2Z2p(1-p)=0.0121.962×0.02×0.98=752.95 Required minimum sample size: 753 participants (round up) plus 10% for non-diagnostic/poor-quality scans and no-shows, i.e. totally 829 participants is needed to screen.
- Ultrasound Acquisition Protocol Equipment & presets
- High-end ultrasound suplex machine Canon Aplio a-series with B-mode, color/power Doppler, spectral Doppler, and microflow/superb microvascular imaging. High-frequency linear transducer PLT-1005BT (5-14 MHz).
- Patient supine, slight neck extension/contralateral head rotation; optimize for the carotid bulb/ICA origin.
Scanning sequence (bilateral)
- B-mode: transverse sweep from distal CCA through bulb into proximal ICA and extracranial carotid artery (ECA); then longitudinal (anterolateral, lateral, posterolateral windows).
- Color Doppler: at low pulse repetition frequency (PRF) to visualize flow separation/recirculation; adjust wall filter and gain to avoid overwriting thin intraluminal structures.
- Spectral Doppler: with angle correction ≤60°, use a sample volume of 1.5-2.0 mm; measure peak systolic velocity (PSV) and end-diastolic velocity (EDV) in standard segments (distal CCA, bulb, proximal ICA).
- Microflow imaging: focused on the posterolateral bulb to delineate the thin shelf/membrane and adjacent flow.
Image storage
- Mandatory cine loops (≥3 cardiac cycles) in longitudinal and transverse views of the bulb/ICA origin, plus still frames with and without color, and spectral Doppler waveforms with angle annotation (same as in protocol of ANTIQUE study - ClinicalTrials.gov ID NCT02360137).
- Label side and projection; record machine make/model, probe, presets. 7) Sonographic Definition of Carotid Web
Definite carotid web:
Inclusion criteria
- Focal echogenic lesion in the carotid bifurcation (15 mm proximally to the flow divider and 15 mm distally)
- The lesion is present (interferes) in the posterior wall
- Echogenicity of the lesion is higher than that of intraluminal blood
- Maximal length of lesions 3.0 mm
- Minimal intraluminal prominence (width) 2.0 mm
- In longitudinal view: The shape of the lesion is shelf-like or valve-like, triangular with the sharpest angle proximally, with the blood flow direction
- In transversal view: Transversal linear defect with echogenic surface projecting in the arterial lumen (the shape should be nest-like)
- Hemodynamic signature: focal flow separation/recirculation or color aliasing immediately distal to the shelf without proportionate atherosclerotic plaque; spectral Doppler may be normal or show subtle focal acceleration without classic stenosis criteria.
Exclusion criteria
- The length is greater than the width
- Visible only in transversal and not longitudinal view
- Presence of carotid plaque (Mannheim consensus) in the posterior wall
Suspected carotid web:
Inclusion criteria
- Focal echogenic lesion in the carotid bifurcation (15 mm proximally to the flow divider and 15 mm distally) 2. Minimal intraluminal prominence (width) 1.5 mm 3. One out of these criteria:
- In longitudinal view: Shape of lesion is shelf-like or valve-like, triangular with the sharpest angle proximally, with the blood flow direction
- In transversal view: Transversal linear defect with echogenic surface projecting in the arterial lumen (the shape should be nest-like)
Exclusion criteria
- Presence of carotid plaque (Mannheim consensus) in the posterior wall
Differential sonographic features to record: typical plaque (echogenic/heterogeneous with surface calcification), carotid diaphragm, dissection flap (mobile, intramural hematoma), carotid web with superimposed thrombus.
- Sonographic Case Definition of Carotid Web
Required equipment/settings (if specified in your criteria):
- Probe/frequency: 5-14 MHz
- Settings: mechanical index of 1.6, 37 fps, Q scan, dynamic range 70
- Patient position: supine position, slight neck extension/contralateral head rotation
Diagnostic categories (tick all that apply):
- Definite CaW - must meet morphology, location, hemodynamics criteria, and exclusions ruled out (plaque, dissection, diaphragm, artifact).
- Probable CaW - meets some morphology criteria and exclusions ruled out (plaque, dissection, diaphragm, artifact).
- Not CaW - meets no criteria for CaW.
Morphologic measurements (standardized):
- Web thickness (mm): ____ (measured at ______)
- Web length/projection into lumen (mm): ____
- Projection angle (°) relative to vessel wall: ____
- Distance from flow divider (mm): ____
- Side: left / right / bilateral
Hemodynamic signatures (as per your thresholds):
- Color Doppler recirculation/aliasing: present / absent (criteria: ______)
- Spectral Doppler acceleration: PSV ___ m/s (cutoff: ___); ICA/CCA ratio cutoff: ___
- Microflow imaging pattern: ______
Differential exclusion checklist (define image features to rule out):
- Atherosclerotic plaque: ______
- Dissection flap/intramural hematoma: ______
- Carotid diaphragm/other membranes: ______
- Artifact (reverberation, blooming): ______
Image acquisition minimums (per side):
- Transverse cine (≥3 cycles) focused on bulb/ICA origin
- Longitudinal cine in ≥2 insonation planes (lat & post-lat)
- Still frames (B-mode ± color) with calipers for all measurements
- Spectral Doppler waveforms (CCA, bulb, proximal ICA) with angle correction ≤60°
Quality grading (apply your rules):
- Grade 1 (excellent) / 2 (diagnostic) / 3 (limited) - use only Grades 1-2 in primary analysis; Grade 3 in sensitivity analysis.
Reader guidance & adjudication using your criteria:
- Two blinded readers score Definite/Probable/Possible/Not CaW; discrepancies resolved by third reader under the same rubric.
- 10% repeat reads for κ/ICC. CRF add-ons (pre-wired to your criteria)
- Checkboxes for each criterion element (present/absent/not evaluable).
- Auto-calculated category (Definite/Probable/Possible/Not CaW) based on boxes ticked.
- Mandatory image IDs linked to each measurement. 8) Training, Blinding, and Adjudication
- Sonographers undergo a standardized training module with exemplar images and checklists.
- Blinding: Operators are blinded to participant clinical data except age/sex; central readers (two expert neurosonologists) are blinded to site and each other.
- Adjudication: Disagreements (probable/possible/absent) resolved by a third senior reader.
- Reliability: 10% random sample re-read for inter-observer agreement (Cohen's κ for categorical calls; ICC for continuous measures).
- Data Collection
- Demographics: age, sex, ethnicity (optional), height/weight.
- Vascular risk factors: smoking status, BP at visit, lipid profile if available, personal history of stroke/TIA/migraine, OCP use (females), recreational drugs, connective tissue disease/FMD history.
- Ultrasound fields: laterality; CaW category (absent/possible/probable), web dimensions (length, thickness, projection angle-estimate), distance from flow divider, presence of superimposed thrombus, plaque descriptors, standard velocities (CCA, bulb, ICA), ICA/CCA PSV ratio, EDV.
- Imaging quality scores and reasons for non-diagnostic studies.
- Validation Substudy
- Participants with definite or possible CaW on DUS plus 1:2 matched DUS-negative controls (matched by age/sex/site) will be invited for CTA within 4 weeks to evaluate concordance (index test: DUS; reference standard: CTA with thin-slice oblique sagittal reconstructions). Outcome: sensitivity/specificity and positive predictive value of DUS criteria. (CTA descriptions of CaW as thin, shelf-like posterior bulb defects guide the reference call.)
- Statistical Analysis Plan
- Weighting: Apply sampling weights for cluster/strata to estimate population prevalence; robust SEs (Taylor linearization) or survey-design GLMs.
- Descriptives: Means/SDs or medians/IQRs; counts/% with 95% CIs.
- Primary analysis: Weighted prevalence and exact (Clopper-Pearson) or Wilson CIs for rare events; compare strata with Rao-Scott χ².
- Regression (exploratory): Survey-weighted Poisson (log link, robust variance) for prevalence ratios of CaW vs candidate covariates.
- Reliability: Cohen's κ with 95% CI (categorical), ICC(2,1) for continuous measures.
- Missing data: Report flow; use complete-case for primary prevalence; multiple imputation for covariate analyses if >5% missing.
- Sensitivity analyses: (i) include possible CaW as positive; (ii) restrict to scans with top quality scores; (iii) per-reader estimates.
- Bias Minimization & Quality Control
- Pre-specified imaging protocol; machine presets harmonized across sites.
- Central training and periodic recalibration; quarterly site audits of randomly selected studies.
- Consecutive sampling within clusters to reduce selection bias; track response rates.
- Maintain blinding; lock image sets before adjudication.
- Ethics and Safety
- Minimal-risk imaging study; no ionizing radiation in the primary protocol.
- Informed consent; separate consent for optional CTA.
- Participants with incidental significant carotid stenosis or suspected thrombus receive counseling and referral per local care pathways.
- Data privacy per GDPR; coded IDs; secure storage.
