Diagnostic Accuracy of Contrast-enhanced Transcranial Doppler for Patent Foramen Ovale Detection in Adults: Systematic Review and Meta-analysis

Abstract Contrast-enhanced transcranial Doppler (c-TCD) is a promising noninvasive method for detecting patent foramen ovale (PFO) in adults, but its diagnostic accuracy compared to the gold standard transesophageal echocardiography (TEE) requires up-to-date evaluation. We conducted a systematic review and meta-analysis of studies from 2015 to 2025 assessing c-TCD for PFO detection in adults, following the PRISMA guidelines. A comprehensive search identified 37 relevant articles; of these, five primary studies met the inclusion criteria for quantitative analysis. Data on sensitivity, specificity, and othervdiagnostic performance metrics were extracted, and study quality was appraised using QUADAS-2. The included studies (mostly cryptogenic stroke patients) indicated that c-TCD had high sensitivity (~95%) and good specificity (~90%) for detecting PFO compared to TEE. In our meta-analysis, the summary sensitivity of c-TCD was 94.8% (95% confidence interval CI: 91%–98%) and the specificity was 89.7% (95% CI: 85%–94%). The pooled positive likelihood ratio was ~9, and the negative likelihood ratio was ~0.06. The diagnostic odds ratio was approximately 150, and the area under the curve of the summary receiver operating characteristic curve was approximately 0.97, reflecting excellent overall accuracy. Contrast TCD demonstrates robust diagnostic performance for PFO detection, approaching that of TEE. A negative result on c-TCD reduces the likelihood of clinically significant PFO in patients with stroke, whereas a positive c-TCD strongly suggests PFO and should prompt confirmatory TEE for anatomical details. These findings support the use of c-TCD as a first-line screening tool in the evaluation of cryptogenic stroke.