cTCD allows estimation of the shunt size by quantification and categorization of the contrast shunted. The results are comparable with shunt quantification using cTEE , , , , ,  and . Large RLS assessed by cTCD have been reported to be associated with a higher risk of first and recurrent stroke, particularly with cryptogenic stroke  and . In contrast, results of a study showed that massive RLS sized ALK inhibitor with TCD
were not an independent risk factor for recurrent stroke . Therefore, the clinical significance of cTCD shunt sizing remains unclear. The impact of cTCD in RLS detection has been studied in a number of conditions other than cerebrovascular disease; however, the grade of evidence from these studies is low to moderate: a significant association was reported between the degree of cTCD sized shunting and the number of signal abnormalities on MRI in asymptomatic sport divers . Divers with RLS show a higher risk of decompression sickness . There is
evidence of an increased prevalence of PFO in patients with migraine with aura , supported by cTCD studies  and . Furthermore, cTCD has selleck products been described to be useful to detect residual shunting following transcatheter closure of a PFO . Depending on methodological factors, cTCD results vary considerably. Therefore, criteria of the examination technique were established by an International Consensus Meeting. Phospholipase D1 The goal was a standardized approach and minimal variability for RLS detection by cTCD . The examination technique recommended by this Consensus Meeting is summarized in Table 1. Fig. 1 shows a video demonstration of a positive contrast study in a patient with large PFO. Additional data are available also from publications summarizing the impact and technique of cTCD for diagnosis of PFO  and . cTCD uses air-containing echo contrast agents (CAs) which normally are
unable to pass the pulmonary capillary bed. The diagnosis of a RLS by cTCD is established if TCD observes microembolic signals after contrast injection. However, the minimal amount of microembolic signals suggestive of a clinically relevant RLS is not established . Different authors require different numbers of microembolic signals for the diagnosis of a PFO. They range from a minimum of one microembolus to more than five microemboli. In addition, the time from contrast injection to signal detection ranges from 6 to 10 cardiac cycles or from 4 s to 24 s ,  and . Most authors used agitated saline solution as contrast agent , , , , , , ,  and  or d-galactose Mb solution (Echovist®) , , , , , , , ,  and . Only few authors used other agents such as Oxypolygelatine (Gelifundol®, Gelofusin®) ,  and .