The baseline TCD pattern may show blunting of the peak systolic wave in patients with severe extracranial disease [29]. More importantly, the TCD may give some insight into the collateral support via the Circle of Willis [30–32]. This information will help the operator better understand the patient’s ability to tolerate cerebral protection systems that may arrest or even reverse the ipsilateral internal carotid artery flow. Niesen et al. reported the utilization of the baseline ratio between the peak systolic velocity in the ipsilateral middle cerebral vessel compared to the contralateral middle cerebral system as a reference for collateral support [33]. However, determination of cerebrovascular reserve (CVR) prior to use of flow arrest and flow reversal cerebral protection systems is not universally felt to be helpful in predicting severe hemodynamic changes during carotid stenting. Spacek et al. utilized TCD to calculate a breath-holding index (BHI) and assessed for reversal of flow in the ophthalmic artery prior to patients undergoing carotid stenting. Their findings demonstrated that pre-procedural TCD testing is not a reliable predictor of hemodynamic changes occurring during proximal protection with carotid stenting in patients with unilateral carotid stenosis [34].

The baseline intracranial flow characteristics could also be important in predicting patients who are at risk for post-procedural reperfusion syndrome and even intracranial hemorrhage. Kablak-Ziembbicka et al. demonstrated that the peak systolic velocity ratio (PSVR) in the ipsilateral middle cerebral artery (iMCA) and contralateral middle cerebral artery (cMCA) predicted cerebral reperfusion injury (CRI) with a combination of an ipsilateral PSVR >2.4 and contralateral PSVR >2.4 being an independent risk factor for CRI [35]. Also, a group out of Greece demonstrated that pre-procedure exhausted cerebrovascular reactivity on ipsilateral TCD was an excellent predictor of reperfusion syndrome [36]. Mori et al. suggested the possibility of utilizing further hemodynamic testing in patients who are at increased risk for intracranial hemorrhage prior to placing them on the table [37]. This may include utilization of carbon dioxide reactivity or VMR testing with Diamox prior to interaction with the lesion.

Transcranial Doppler allows us to continuously monitor two important parameters during carotid artery stenting. The first is related to ensuring preserved middle cerebral flow velocity and pulse volume. The utilization of a proximal or distal occlusive device for cerebral protection does result in interruption or reversal of flow in the ipsilateral internal carotid artery [38]. During internal carotid artery flow arrest or reversal, a dramatic drop in middle cerebral flow velocity on TCD may precede the clinical hemispheric symptoms that can be seen in patients with severe contralateral disease or inadequate collateral support due to an incomplete Circle of Willis. This provides the operator with additional insight as to how balloon occlusion will be tolerated and whether the procedure will need to be staged.

Currently, there are three flow interruption embolic protection devices that have been systematically studied. One device is a distal occlusion balloon protection system called the GuardWire Temporary Occlusion and Aspiration System (Medtronic Corporation, Minneapolis, MN). This device is a low-pressure balloon on a 0.014″ wire that can be navigated across the lesion and then inflated to occlude the internal carotid artery during transcatheter intervention [20]. Utilization of this type of distal balloon occlusion system has proven to be effective on reducing the risk of embolization. However, Nadim Al-Mubarak et al. have shown with TCD release of particles during balloon deflation that is likely related to inadequate particle retrieval from the cul-de-sac around the balloon [39]. There are two proximal protection devices, and these include the Mo MA Ultra (Medronic Corporation, Minneapolis, MN) and Gore Flow Reversal System (W.L. Gore & Associates, Flagstaff, AZ).

Parodi demonstrated with TCD the ability to completely reverse flow in the middle cerebral artery by transcatheter occlusion of the ipsilateral common and external carotid artery while at the same time creating negative pressure at the tip of the guiding sheath as noted in Fig. 16.4 [40]. This may have significant implications for optimizing cerebral protection during carotid stenting and ultimately could facilitate clot retrieval during transcatheter treatment of acute stroke.

It should be noted that TCD suggests that middle cerebral artery flow is reduced by 10–30% when a distal filter is opened due to filter-induced flow resistance [41]. In patients with an intact Circle of Willis undergoing carotid stenting with a protection system that preserves flow (i.e., filter), the sudden interruption of flow to the ipsilateral middle cerebral artery could be an ominous finding suggesting a large embolic event or spasm in the internal carotid artery proper. Also, filter systems do have a threshold of particulate debris based on the filtered design and size [42]. If the volume of embolic debris exceeds the filter threshold, then occlusion can occur, and this may be heralded by changes on TCD. Similar changes can occur if there is spasm in the ipsilateral internal carotid artery system related to the distal protection filter [27].

The second variable that is monitored by TCD during carotid artery stenting is the occurrence of microemboli signals (MES). The reflective properties of microembolic material as it passes through the middle cerebral artery are translated into sudden signal shifts that are depicted as high-velocity transient spikes on the continuous Doppler recording [43–45]. These high-intensity signals may represent the egress of small particles or microembolic debris into the ipsilateral hemisphere [46]. It is difficult to differentiate artifact from small air bubbles versus true embolic debris, and that is one of the limitations of this technology [47–49]. Ex vitro studies by Coggia et al. and Ohki et al. have provided significant insight into when particles are released during different stages of the procedure [50, 51]. The peak embolic risk during angioplasty in the ex vitro model appears to be during balloon deflation [50]. Similar findings are seen in vivo with continuous TCD during carotid stenting at the time of balloon deflation [52, 53]. In our experience, MES are seen during all stages of carotid stenting with or without protection even with navigation of a 0.014″ wire across the lesion (Fig. 16.5). Paradoxically, in a study of over 500 patients who underwent CAS with TCD, there were actually a higher number of MES in the patients with filters in comparison to those without protection, and the clinical significance of these findings has not been clearly defined [54].

TCD has been used to compare proximal protection (Mo.Ma system and Gore Flow Reversal System) to distal protection with a filter system [55, 56]. Proximal protection was demonstrated in two studies to result in fewer MES and then was demonstrated when distal protection with a filter system was used [55, 56].

In the context of academic applications, a new approach to TCD has been advocated by Garami et al. whereby dual measurements are recorded simultaneously during CAS to evaluate proximal versus distal protection devices [57]. One transducer is positioned in the traditional transcranial window, while another is used to sample flow in the internal carotid via a submandibular window. Also, Stoner-Duncan et al. advocated use of a multichannel video system to precisely determine when emboli dislodged in real time. They developed a method to simultaneously record fluoroscopic images, TCD data, vital signs, and a digital video of the patient/physician to permit accurate analysis of the data [58].

Some authors have followed TCD with serial interval studies during the first 12 h following carotid stenting [59, 60]. Our center feels that this may be particularly important in patients who are at increased risk for intracranial hemorrhage. The pre-procedural risk factors for reperfusion syndrome and/or intracranial hemorrhage include contralateral severe carotid disease or occlusion, baseline high-grade stenosis or “string sign” with slow flow, hypertension during the carotid stenting procedure, and baseline decrease of vaso-reactivity [61]. Figure 16.6 details the TCD hemodynamic sequence of a patient who developed the typical reperfusion syndrome complicated by intracranial hemorrhage during our early experience with unprotected carotid stenting 15 years ago.

Few studies have actually performed continuous TCD in the early postoperative after carotid stenting. However, it seems that MES are common during the recovery period after carotid stenting as well. Piorkowski et al. found that 38% (51 or 134) of patients who underwent carotid artery stenting had relevant MES in the first hour after stenting [62]. Three factors were found to be associated with increased post-interventional MES: symptomatic lesion, elevated total cholesterol, and aspirin monotherapy [62]. Both dual antiplatelet therapy (OR 5.6, p < 0.0005) and asymptomatic lesions (OR 2.6, p < 0.05) were independent predictors for the absence of post-interventional MES [62]. It has been proposed that the use of closed-cell stents rather than open-cell stents may decrease the risk of post-interventional embolization. However, in a randomized study comparing both types of stents by Timaran et al. using TCD to assess for MES after carotid stenting, the use of open-cell versus closed-cell stents for carotid stenting did not affect the frequency of cerebral embolization [63].

Microembolic signals detected during carotid endarterectomy have been associated with decrease in cognitive function [64]. Similarly, MES with so-called embolic storms during different stages of carotid stent procedures are associated with ipsilateral defects on early follow-up diffusion-weighted MRI scan [65–69]. Currently, there is very little data with regard to cognitive function in patients following protected carotid artery stenting, but this is a concern. Interestingly, in a small subgroup analysis of patients during the carotid and vertebral artery transluminal angioplasty study (CAVATAS), there were similar outcomes on neurologic testing in both the carotid endarterectomy and carotid stenting groups in spite of a higher number of MES in the latter [70]. Also, cognitive impairment has been demonstrated to improve after stenting of severe symptomatic carotid stenosis, and one of the authors’ theories was that TCD demonstrated significant improvement in the hemodynamics of the treated carotid artery [71].

The threshold or “safe” size for microemboli has not been clearly defined. Early work suggests that any particles more than 50 microns in size will not circulate to the venous cerebral system and thus by definition will cause some arteriolar occlusions [72]. Significant work on this front has been done to better understand the decrease in cognitive function that one sees after coronary artery bypass surgery. It appears that based on a postmortem study by Moody et al., the particles causing decreased cognitive function after a coronary artery bypass surgery are less than 70 microns in size [73]. This is particularly important to understand since most distal protection filters have a pore size of 100–120 microns.

The differentiation of air bubbles from true atheroemboli has been very difficult. Several techniques have been described including a defined threshold of greater than ten hits in a sequence [28]. Different mathematical sequences have also been defined through the years; however, there currently is no ideal way to differentiate these in vivo [48–51].

There are certain stages of the procedure where contamination from air artifact would be less likely. For example, crossing the lesion with the wire as noted in Fig. 16.5 should not be associated with air embolization and is likely true microemboli. Also, many centers have reported the highest numbers of emboli occur with pre-dilatation or post-dilatation as the balloon is deflated, and it is also unlikely there is significant trapped air or artifact during this time as depicted in Fig. 16.7. In difference one typically sees scattered MES during contrast injections that is related to microbubbles in the contrast (Fig. 16.8).

Most of the carotid stents used today are self-expanding stents made of nickel titanium with an outer constraining sheath that has to be retracted for deployment. There is always a high volume of MES with retracting the sheath housing of the self-expanding stent, and some authors have suggested that this is related to the shear force of a stent against the plaque [28]. However, we feel this is related to trapped air within the matrix of the stent and, thus, less likely of pathologic concern (Fig. 16.9).