• magnetic resonance imaging;
  • paradoxical embolism;
  • patent foramen ovale;
  • silent brain infarction;
  • transcranial Doppler


In healthy elderly people, silent brain infarctions (SBIs) have been recognized as common lesions. In this study, we evaluated the association between SBI located outside the perforating artery territory (PAT) and paradoxical embolism detected by agitated saline transcranial Doppler (TCD) monitoring in healthy subjects.


This was a prospective observational study undertaken by a university health promotion center for healthy subjects and by a university stroke center for acute stroke patients. We defined SBI as evidence on fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or more infarcts, without history of corresponding stroke or transient ischaemic attack. We also evaluated in all subjects the neuroimaging indicator of microangiopathy leukoaraiosis (LA). This study is registered with, number NCT01429948.


Amongst 1103 consecutive healthy adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT, suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS was similar to cryptogenic embolic stroke (62.0%, = 0.056), but higher than in patients with other stroke subtypes (36.2%, = 0.021). Amongst subjects with SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01–3.14; = 0.046).


Our results suggest that paradoxical embolism may play an important role in the development of SBI outside the PAT in apparently healthy adults.