Microembolic signals (MESs), detected via transcranial Doppler ultrasonography, play a pivotal role in diagnosis and monitoring of cerebrovascular diseases. Unlike imaging modalities, such as magnetic resonance imaging or computed tomography, MESs offer real-time insights into embolic events, providing unique clinical and prognostic information. This capability has made MESs an invaluable tool for assessing the risk of stroke, understanding embolic complications, and evaluating the effectiveness of therapeutic interventions in both routine and specialized clinical settings.

The clinical and research landscape surrounding MESs has evolved significantly over the past decade, driven by advancements in diagnostic technologies and an increasing understanding of their role in cerebrovascular and systemic conditions. MESs have emerged as a critical biomarker for evaluating embolic risk, thereby guiding therapeutic decisions and predicting outcomes across a wide range of patient populations and clinical scenarios. This review aimed to summarize the findings from the past decade, providing a comprehensive overview of the current state of knowledge regarding MESs. By consolidating these insights, this review seeks to propose future directions to enhance the clinical utility of MESs as a diagnostic and prognostic tool in modern medicine.

The Basic Identification Criteria of Doppler Microembolic Signals established by the Consensus Committee of the Ninth International Cerebral Hemodynamic Symposium in 1995 remain largely unchanged and continue to serve as the foundation for identifying MESs.¹ These criteria define MESs as unidirectional short-duration signals (<300 ms), with significant increases in intensity (>3 dB) above the background blood flow, occurring randomly throughout the cardiac cycle and producing a characteristic audible sound (often described as a “whistle,” “chirp,” or “click”). However, for heightened specificity, some studies have incorporated a higher threshold, such as a 9.0 dB threshold.^2,3

A systematic literature search was conducted using PubMed to identify studies related to MESs. The search utilized the terms “(Microembolic [Title] OR (high-intensity transient [Title]))” and included results published between January 2014 and October 2024. To ensure relevance and quality, the following exclusion criteria were applied after reviewing titles and abstracts: non-clinical research articles (e.g., reviews, meta-analyses, clinical trial protocols, editorials, and case reports), studies conducted on non-human subjects, articles unrelated to transcranial Doppler sonography, and those not focused on MES.

A total of 327 articles met the criteria for the search terms and of these articles, 95 were published between January 2014 and October 2024 (Fig. 1). From these 95 articles, 60 were finally included after the exclusion of 35 articles (17 non-clinical articles, 8 studies involving non-human subjects, 2 articles unrelated to transcranial Doppler sonography, and 5 articles not focused on MESs). A schematic representation of the key topics of the included articles is provided in Fig. 2.

MESs are more frequently observed in cases with significant stenosis in the extracranial carotid artery and middle cerebral artery.^4,5 Stenosis involving these arteries creates areas of turbulent and disrupted blood flow, which increases shear stress and can damage the endothelial lining of blood vessel walls.^6,7 This endothelial injury promotes platelet activation and aggregation, as well as the formation of microthrombi. Furthermore, the narrowed arterial lumen increases the likelihood of embolization as fragments of atherosclerotic plaque or thrombi detach and travel distally. These microemboli, formed through a combination of plaque rupture, thrombus formation, and local hemodynamic changes, are detected as MESs.⁸ Vulnerable extracranial carotid plaques, represented by lipid-rich plaques or luminal thrombi upon histopathological examination after a carotid endarterectomy, are associated with MESs.⁹ MES frequency during carotid endarterectomy is associated with vulnerable characteristics in plaque magnetic resonance imaging.¹⁰ However, plaque characteristics on magnetic resonance imaging are not associated with MESs in patients with mild-to-moderate symptomatic plaques.¹¹ MESs are more commonly detected in cases with a short delay between stroke onset and monitoring, as well as in cases of symptomatic stenosis compared to asymptomatic lesions, affecting both intracranial and extracranial arteries.^5,7,12 The use of dual antiplatelet therapy or statins prior to a stroke, particularly in patients with large artery atherosclerosis, is associated with a decreased MES frequency, suggesting a role in plaque stabilization.^13-15

Underlying conditions, such as atrial fibrillation, are also known to be associated with MESs.¹⁶ Patients who experienced an embolic stroke with undetermined etiology show a higher frequency of MESs than those with other etiologies.¹⁷ MESs are also detected in patients with essential thrombosis or insulin resistance.^18,19 Additionally, they are more frequent in patients who experience migraines with higher cortical dysfunction during aura than in healthy controls and in those with only visual or somatosensory symptoms.²⁰ However, these associations were based on limited evidence from single-center studies, and a direct causal relationship has not been established. Patients who had higher cortical dysfunction, such as language and memory impairment, during aura had more frequent MESs than the other control groups (29.4% vs. 3.2% and 5.9%).

MESs have been increasingly recognized as a valuable biomarker for predicting stroke risk, assessing disease progression, and guiding therapeutic interventions. MESs have been linked to an increased risk of stroke in the future and poorer outcomes in patients who have experienced an ischemic stroke or transient ischemic attack.² In a meta-analysis, there was a two-fold increase in the chance of a new cerebral infarction when MESs were detected. 21 Specifically, not only stroke recurrence (hazard ratio 4.90) but functional disability (discharge-modified Rankin Scale 3–6, odds ratio 3.3) and longer hospital stays (approximately 3 days more) were associated with MESs. A similar association was also observed in patients who experienced strokes due to large artery occlusion, who underwent endovascular thrombectomies.²² Notably, MESs were detected in 65% of patients who underwent EVT, more frequently in patients with ipsilateral carotid stenosis, carotid occlusion, or inadequate or no collaterals. The presence MESs after thrombectomy are associated with a significantly higher incidence of composite vascular events (odds ratio 4.85) and worse functional outcomes at a threshold of 5 MESs per hour (3 month modified Rankin Scale >2, 76.9% vs. 34.7%). The risk of cognitive decline was also associated with the presence of MESs in patients with neurological disorders.²³

MESs may also be used to assess the embolic risk of underlying diseases. MESs are found more frequently in patients with moyamoya disease who experienced recent ischemic events and are predictive of future ischemic events, suggesting a potential link between MESs and stroke risk in moyamoya disease.^24-26 A change to an antiplatelet therapy regimen was evaluated in patients with moyamoya disease who had MESs (21 patients).²⁶ Follow-up monitoring showed loss of MESs for all patients after the antiplatelet regimen change, underscoring MESs as a biomarker for guiding antiplatelet therapy. Similarly, patients with atrial fibrillation who exhibit MESs are associated with a higher risk of embolism.¹⁶ Patients with active cancer and acute stroke are at risk for increased mortality and infarction involving multiple arterial territories if MESs are detected during monitoring.²⁷ MESs are also related with ischemic complications after unruptured intracranial aneurysm coiling.²⁸ They can be detected in 65.7% of patients immediately after coiling and in 36.8% of patients 24 hours post-coiling. The presence of MESs at both time points show a strong correlation with the number of ischemic lesions identified on magnetic resonance imaging. This was a single-center study involving 45 patients, and further validation is required.

MESs can serve as a surrogate marker for embolism, particularly in scenarios where embolic complications, such as stroke, occur infrequently. For example, MES monitoring during high embolic risk procedures allows for the evaluation of different procedural techniques to determine which approach minimizes embolic events. This methodology enables statistically significant findings to be achieved with smaller sample sizes. Numerous studies have been published regarding assessment of embolic risk during catheter ablation for atrial fibrillation.^29-33 Embolic risk differences between procedural techniques were assessed using MESs during transcatheter aortic valve implantation.^34-36 MESs have been utilized as a marker for plaque stability in evaluating imaging modalities such as FDG-PET CT, contrast-enhanced ultrasound, and Superb Microvascular Imaging ultrasound.^37-39 They have also been employed to assess embolism risk using laboratory values as predictors, such as C-reactive protein, osteoprotegerin, and CXCL16 cytokine levels.^40-42 The influence of genetic polymorphisms in PTPN22, NLRP3, and OPG genes on embolism risk has been studied using MESs.^43-45 Additionally, MES have been used to understand the impact of platelet reactivity on embolic risk in carotid stenosis.^46-48

Despite the frequent detection of MESs during specific medical and surgical interventions, several studies have reported no significant association with clinical outcomes. For instance, MESs observed during carotid endarterectomy do not correlate with the development of new brain lesions post-procedure, possibly due to the small number of events (4 out of 160 patients).⁴⁹ Similarly, while MESs are commonly detected during pulmonary vein isolation and are known to be associated with brain lesions or neurologic outcomes,^29,50 they were not linked to silent brain lesions, cognitive changes, or stroke in one multicenter study.⁵¹ Additionally, although cognitive dysfunction is commonly noted following left heart catheterization, it is not associated with the number of microemboli detected during the procedure.⁵² These results may imply that, in cardiac procedures, neurologic outcomes may be influenced not only by the MES count, but also by procedural or individual factors.

Recent advancements have expanded the use of MES monitoring into specialized clinical contexts. In infants undergoing cardiac catheterization and surgery, MES monitoring has been successfully performed, providing insights into cerebral embolic risks during these procedures.^53,54 However, MESs detected during infant cardiac surgery is not directly linked to specific surgical maneuvers.⁵⁵ Furthermore, a novel algorithm capable of differentiating gaseous from solid embolic signals has been developed, potentially enhancing MES monitoring during cardiac surgeries.⁵⁶ MES detection at the vertebrobasilar junction in patients with vertebral artery dissection was previously performed, implying MES monitoring at the vertebrobasilar junction as a feasible option.⁵⁷

Recent studies surrounding MESs indicate the clinical potential of transcranial monitoring for MESs. MES detection provides critical insights into the risk of stroke, embolic complications, and plaque stability, making it an indispensable tool in various clinical scenarios. However, its utility is currently limited by practical constraints, including the expertise required for interpretation and the short duration of monitoring.^58,59 As a result, MES monitoring is not performed as frequently as its clinical potential might warrant. Advanced wearable and wireless technologies may present an exciting opportunity to overcome these limitations.⁶⁰ Portable devices for long-term MES monitoring may enhance early detection of embolic events and broaden their clinical utility. By improving accessibility and enabling outpatient use, these advancements may support more comprehensive monitoring and personalized management of embolic risks, although further research is needed.