Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome

Discussion

Using whole-brain SWI, we found multiple intracranial thrombi in 24 of 324 patients with acute stroke with the SVS (7.4%) before initiation of any thrombolytic therapy. Most distal thrombus fragments (95.8%) affected the same vascular territory distal to the proximal occluding thrombus and were therefore a priori invisible with normal angiographic techniques. We found significant associations between the presence of multiple intracranial thrombi and a higher NIHSS score on admission as well as larger ischemic areas on pretreatment DWI. The presence of fragmented thrombi was a predictor of unfavorable clinical outcome at 3 months.

A study that analyzed the histologic structure of clots extracted by endovascular means by using the Merci retriever (Concentric Medical, Mountain View, California) reported that in 64% of cases, thrombi were retrieved in multiple fragments.¹¹ It is likely that the prevalence of fragmented thrombi had been lower before mechanical disruption of the clot during deployment and retraction of the thrombectomy device. This supposition is supported by our in vivo studies demonstrating thrombus fragmentation and distal embolization during retrieval of the initially single thrombus with distal thrombectomy devices.¹²

Although our results are based purely on thrombus fragmentation before thrombolytic treatment, it could be speculated that iatrogenic thrombus fragmentation might have a similarly negative impact on outcome. This may, among other contributing factors, explain the disappointing clinical outcome in studies that used thrombus fragmentation techniques exclusively (Multi Mechanical Embolus Removal in Cerebral Ischemia, Penumbra Pivotal Stroke Trial, Mechanical Retrieval and REcanalization of Stroke Clots Using Embolectomy trials)^13⇓–15 or in part (Interventional Management of Stroke III, SYNTHESIS Expansion [A randomized controlled trial between loco-regional intra-arterial and systemic intravenous thrombolysis with Alteplase in acute ischemic stroke]).^16,17 The SYNTHESIS Expansion study reported that thrombus fragmentation with a microguidewire was performed in approximately two-thirds of patients.¹⁷ In contrast, the goal of current mechanical thrombectomy in acute stroke is removal of the thrombus en bloc with the lowest possible rate of thrombus fragmentation, as applied and improved in experienced stroke centers.^10,18,19

In our series, good collaterals as assessed on DSA were found in fewer patients with multiple intracranial thrombi, though the difference was not significant. No additional differences in other well-known predictors of outcome were found between patients with and without multiple thrombi. There is evidence from multiple studies that good leptomeningeal collaterals reduce and slow penumbral tissue loss, resulting in better clinical outcome.^20,21 When one considers the differences in collateral status between patients with and without multiple fragments, the probable role of autolysis should be discussed. Zanette et al²² reported that spontaneous lysis occurs in a high percentage of patients with distal MCA occlusions, similar to the sites where most of the distal thrombus fragments were found in our cohort. Because good collaterals were seen less often in patients with multiple thrombus fragments than in those with a single thrombus, one could hypothesize that fewer endogenous thrombolytic factors may have reached the distal thrombus fragments in patients with poor collateralization, resulting in the persistence of these fragments.

Thrombus burden must be taken into account when looking for factors that could explain the differences in outcome. Total clot length, defined as the combined length of the primary occluding thrombus and the distal thrombus fragments, was significantly higher in patients with fragmented thrombi compared with those with a solitary thrombus. It remains unclear whether longer thrombi are more likely to fragment or distal fragments lead to secondary clot formation due to stagnation of blood flow, thus increasing total clot length. A recent study assessed clot burden in patients with anterior circulation stroke on T2*-weighted imaging by using a scoring system based on the vessel segments that were affected by thrombotic material. Patients with fewer and more distal vessel segments involved had a higher revascularization rate and were more likely to have favorable clinical outcome.²³ Because absolute thrombus length was not part of the scoring system, the comparability with our results is limited. One has to consider that assessment of thrombus burden by measuring the total length of thrombus fragments could result in overestimation in patients with multiple thrombi. Migration of distal thrombus fragments to smaller-sized vessels may result in reorientation and elongation of distal thrombi, resulting in a total clot length disproportionate to total clot volume.

TOF-MRA, first-pass gadolinium-enhanced MRA, and DSA detected only a minority of distal thrombus fragments seen on SWI. The lower yield of these imaging techniques in the detection of distal thrombus fragments most likely results from their dependence on the presence of blood flow or contrast media, both of which are usually reduced or absent distal to the primary vessel occlusion. Besides DWI and imaging of the whole angioarchitecture from the aortic arch up to distal branches of the cerebral arteries, imaging of the thrombus and its fragments with SWI has become a standard sequence of our stroke protocol due to its high therapeutic relevance.⁵

Our study has some limitations. Image analysis was only performed in consensus. In our experience, the SVS and distal thrombus fragments are easily detectable and we did not deem it necessary to additionally assess interobserver variability. Furthermore, each MR imaging study was routinely evaluated by a neuroradiologist and radiologist in training, and the findings were documented in our PACS. In 16 of the 24 patients (66.7%) with multiple thrombi on SWI, a distal vessel occlusion or thrombus fragment or both separate from the primary occlusion had already been described in the radiology report. Most interesting, in the 8 patients in whom distal thrombus fragments were not described initially, the fragments were located in closer proximity to the primary thrombus than in those in whom the distal occlusion was mentioned (7.0 ± 4.0 versus 24.2 ± 15.9 mm). One could speculate that these fragments were either harder to detect or had not been considered important enough to be described in the radiology report. In this single-center study, data from imaging were partly analyzed retrospectively. The small size of the patient group with fragmented thrombi limits the generalizability of the results. Evaluation of ICA and basilar artery thrombi on SWI was greatly limited by the extensive susceptibility artifacts in the proximity of the skull base.