Emma M.L. Chung

Embolus Trajectory Through a Physical Replica of the Major Cerebral Arteries

Background and Purpose— The observed distribution of cerebral infarcts varies markedly from expectations based on blood-flow volume or Doppler embolus detection. In this study, we used an in vitro model of the cerebral arteries to test whether embolus microspheres encountering the circle of Willis are carried proportionally to volume flow or express a preferred trajectory related to arterial morphology or embolus size. Methods— Our model consisted of a patient-specific silicone replica of the cerebral macrocirculation featuring physiologically realistic pulsatile flow of a blood-mimicking fluid at approximately 1000 mL/min and an input pressure of approximately 150/70 mm Hg. Particles of 200, 500, and 1000 &mgr;m diameter with equivalent density to thrombus were introduced to the carotid arteries and counted on exiting the model outlets. Results— The middle cerebral arteries (MCAs) of the replica attracted a disproportionate number of emboli compared with the anterior cerebral arteries; 98%±3% of 1000 &mgr;m and 93%±2% of 500 &mgr;m emboli entered the MCA compared with 82%±5% of the flow. The observed distribution of large emboli was consistent with the ratio of MCA:anterior cerebral artery infarcts, approximately 95% of which occur in territories supplied by the MCA. With decreasing embolus size, the distribution of emboli approaches that of the flow (approximately 89% of 200 &mgr;m emboli took the MCA). Conclusions— Embolus trajectory through the cerebral arteries is dependent on embolus size and strongly favors the MCA for large emboli. The 70:30 ratio of MCA:anterior cerebral artery emboli observed by Doppler ultrasound is consistent with the trajectories of small emboli that tend to be asymptomatic.

Risk Factors Associated with Cognitive Decline after Cardiac Surgery: A Systematic Review

Modern day cardiac surgery evolved upon the advent of cardiopulmonary bypass machines (CPB) in the 1950s. Following this development, cardiac surgery in recent years has improved significantly. Despite such advances and the introduction of new technologies, neurological sequelae after cardiac surgery still exist. Ischaemic stroke, delirium, and cognitive impairment cause significant morbidity and mortality and unfortunately remain common complications. Postoperative cognitive decline (POCD) is believed to be associated with the presence of new ischaemic lesions originating from emboli entering the cerebral circulation during surgery. Cardiopulmonary bypass was thought to be the reason of POCD, but randomised controlled trials comparing with off-pump surgery show contradictory results. Attention has now turned to the growing evidence that perioperative risk factors, as well as patient-related risk factors, play an important role in early and late POCD. Clearly, identifying the mechanism of POCD is challenging. The purpose of this systematic review is to discuss the literature that has investigated patient and perioperative risk factors to better understand the magnitude of the risk factors associated with POCD after cardiac surgery.

Enhanced Detection of Thromboemboli With the Use of Targeted Microbubbles

Background and Purpose— Targeted ultrasound contrast agents have recently been developed to adhere selectively to specific pathogenic materials such as plaque or thrombus. Administration of such microbubbles has potential to aid transcranial Doppler ultrasound (TCD) detection of emboli and to act as markers for distinguishing one embolic material from another. The purpose of this study was to investigate whether TCD detection of circulating thrombus emboli would be enhanced by the addition of targeted microbubbles. Methods— Binding of microbubbles to the surface of the thrombus was confirmed by scanning electron microscopy. Targeted and control bubbles were then introduced to thrombus and tissue-mimicking material circulated under pulsatile-flow conditions in an in vitro flow rig. Embolic signal intensities before and after introduction of the bubbles were measured by TCD. Results— Targeted microbubbles enhanced TCD signal intensities from thrombus emboli by up to 13 dB. The bubbles were capable of binding to moving thrombus when injected into the flow circuit in low concentrations (≈36 bubbles per 100 mL) and were retained on the thrombus under pulsatile-flow conditions. Signal intensities from similarly sized pieces of tissue-mimicking material were not enhanced by injection of targeted bubbles. Conclusions— Injection of appropriately targeted microbubbles significantly enhances TCD detection of circulating thrombus emboli in vitro.

Revealing the mechanisms underlying embolic stroke using computational modelling

Computational forecasting of arterial blockages in a virtual patient has the potential to provide the next generation of advanced clinical monitoring aids for stroke prevention. As a first step towards a physiologically realistic virtual patient, we have created a computer model investigating the effects of emboli (particles or gas bubbles) as they become lodged in the brain. Our model provides a framework for predicting the severity of microvascular obstruction by simulating fundamental interactions between emboli and the fractal geometry of the arterial tree through which they travel. The model vasculature consisted of a bifurcating fractal tree comprising over a million branches ranging between 1 mm and 12 microm in diameter. Motion of emboli through the tree was investigated using a Monte Carlo simulation to evaluate the effects of the embolus size, clearance time and embolization rate on the number and persistence of blocked arterioles. Our simulations reveal with striking clarity that the relationship between embolus properties and vascular obstruction is nonlinear. We observe a rapid change between free-flowing and severely blocked arteries at specific combinations of the embolus size and embolization rate. The model predicts distinct patterns of cerebral injury for solid and gaseous emboli which are consistent with clinical observations. Solid emboli are predicted to be responsible for focal persistent injuries, while fast-clearing gas emboli produce diffuse transient blockages similar to global hypoperfusion. The impact of solid emboli was found to be dramatically reduced by embolus fragmentation. Computer simulations of embolization provide a novel means of investigating the role of emboli in producing neurological injury and assessing effective strategies for stroke prevention.

Thrombus size and Doppler embolic signal intensity.

Background: Migration of thrombus through the cerebral arteries is a common cause of stroke. Thrombus emboli can be detected non-invasively using Doppler ultrasound, but even where the embolus composition is known, there is currently no method for estimating the size of an embolus based on the returned ultrasound signal. Here we report the results of in vitro experiments investigating the relationship between size and embolic signal intensity for fresh thrombus emboli with a view to estimating the sizes of thrombi detected following carotid surgery. Method: Thrombi were formed from whole blood using the ‘Chandler loop’ method under flow conditions similar to those associated with arterial thrombus formation in vivo. A total of 390 Doppler embolic signals were then measured from 37 pieces of thrombus circulated in a pulsatile closed-flow circuit. The dimensions of each of the thrombi were measured before and after circulation using an optical microscope. Relationships between thrombus size and embolic signal properties were then investigated using standard statistical methods with a view to size estimation of thrombi during clinical monitoring. Results: Although embolic signals generally became more intense with increasing thrombus size, strong oscillations due to resonance effects were observed. Pearson tests revealed strong positive correlations between embolus diameter, signal intensity and duration (r > 0.8, p ≤ 0.01). Conclusions: This study provides experimental evidence supporting theoretical predictions relating Doppler embolic signal intensity to thrombus size. In our discussion, we tentatively suggest how this information might be used to size emboli in clinical practice.

Impact of Perioperative Infarcts After Cardiac Surgery

Background and Purpose— Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and preexisting cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition. Methods— Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery patients. The burden of preexisting versus new ischemic lesions was quantified and compared with the results of baseline and postoperative neuropsychological testing. Results— After surgery, new lesions were identified in 31% of patients, averaging 0.5 lesions per patient (67 mm3 [0.004%] of brain tissue). Patients with preexisting lesions were 10× more likely to receive new lesions after surgery than patients without preexisting lesions. Preexisting ischemic lesions were observed in 64% of patients, averaging 19.4 lesions (1542 mm3 [0.1%] of brain tissue). New lesions in the left hemisphere were significantly smaller and more numerous (29 lesions; median volume, 44 mm3; volume range, 5–404 mm3) than those on the right (10 lesions; median volume, 128 mm3; volume range, 13–1383 mm3), which is consistent with a cardioembolic source of particulate emboli. Overall, the incidence of postoperative cognitive decline was 46% and was independent of whether new lesions were present. Conclusions— New lesions after cardiac surgery added a small (≈4%) contribution to the burden of preexisting cerebrovascular disease and did not seem to affect cognitive function. Clinical Trial Registration— URL: http://public.ukcrn.org.uk. Unique identifier: UKCRN ID: 11702.

Transcervical carotid stenting with dynamic flow reversal demonstrates embolization rates comparable to carotid endarterectomy

Purpose: To evaluate a series of patients treated electively with carotid endarterectomy (CEA), transfemoral carotid artery stenting with distal filter protection (CASdp), and transcervical carotid stenting with dynamic flow reversal (CASfr) monitored continuously with transcranial Doppler (TCD) during the procedure to detect intraoperative embolization rates. Methods: Thirty-four patients (mean age 67.6 years; 24 men) with significant carotid stenosis underwent successful TCD monitoring during the revascularization procedure (10 CEA, 8 CASdp, and 16 CASfr). Ipsilateral microembolic signals were segregated into 3 phases: preprotection (until internal carotid artery cross-shunted or clamped if no shunt was used, filter deployed, or flow reversal established), protection (until clamp/shunt was removed, filter retrieved, or antegrade flow reestablished), and postprotection (after clamp/shunt or filter removal or restoration of normal flow). Results: CASdp showed higher embolization rates than CEA or CASfr in the preprotection phase (p<0.001). In the protection phase, CASdp was again associated with more embolization compared with CEA and CASfr (p<0.001). In the postprotection phase, no differences between the revascularization therapies were observed. CASfr and CEA did not show significant differences in intraoperative embolization during any of the phases. Conclusion: TCD recordings demonstrated a significant reduction in embolization to the brain during transcervical carotid artery stent placement with the use of dynamic flow reversal compared to transfemoral CAS using distal filters. No significant differences in microembolization could be detected between CEA and CASfr. The observed lower embolization rates and lack of adverse events suggest that transcervical CAS with dynamic flow reversal is a promising technique and may be the preferred method when performing CAS.

Transcranial Doppler Embolus Detection: A Primer:

Blood clots and pieces of plaque can detach from the insides of arteries and move to the brain with devastating consequences. In this primer, I describe how this process of embolization can be detected by harnessing the Physics of transcranial Doppler ultrasound.

Intraoperative Embolization and Cognitive Decline After Cardiac Surgery: A Systematic Review.

Since the advent of cardiac surgery, complications have existed in many forms. Recent work has focused on the safety of current cardiac surgery with particular emphasis on cognitive outcomes. Cardiopulmonary bypass has improved the safety of operative practice; however, increasing concern surrounds the measurable and immeasurable impact embolization has on the brain. New ischemic lesions have been associated with distant emboli, which intraoperatively enter the cardiovascular system. This has prompted better characterization of the nature of emboli manifesting as cognitive impairment postoperatively. The difficulty in attributing causation relates to the subclinical damage that does not necessarily manifest as clinical stroke. Transcranial Doppler has become an important tool in documenting cerebral emboli during surgery. The purpose of this systematic review is to focus on the current literature to improve our understanding of the impact embolization has on the brain. We also aim to investigate which cardiac interventions hold the greatest burden of embolic load and how previous literature has investigated the impact of emboli on cognition by monitoring emboli during specific cardiac interventions. Significant intraoperative factors such as the cardiopulmonary bypass machine and surgical interventions have been highlighted to summarize the current literature associating cerebral embolization with these factors and postoperative cognitive outcomes. The findings of this review report that the current literature is divided as to whether the impact of embolization during cardiac surgery has any adverse impact on cognition. This review highlights that the ultimate goal of improving cognitive safety will involve further careful consideration of multifactorial events.

Sizing Gaseous Emboli Using Doppler Embolic Signal Intensity

Extension of transcranial Doppler embolus detection to estimation of bubble size has historically been hindered by difficulties in applying scattering theory to the interpretation of clinical data. This article presents a simplified approach to the sizing of air emboli based on analysis of Doppler embolic signal intensity, by using an approximation to the full scattering theory that can be solved to estimate embolus size. Tests using simulated emboli show that our algorithm is theoretically capable of sizing 90% of “emboli” to within 10% of their true radius. In vitro tests show that 69% of emboli can be sized to within 20% of their true value under ideal conditions, which reduces to 30% of emboli if the beam and vessel are severely misaligned. Our results demonstrate that estimation of bubble size during clinical monitoring could be used to distinguish benign microbubbles from potentially harmful macrobubbles during intraoperative clinical monitoring.