By Johannes Kaesmacher, MD, University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern and Grégoire Boulouis, MD MSc, Department of Neuroradiology, Université Paris Descartes, Sainte Anne Hospital.

Treating diseases usually relies on characterizing a pathologic condition as specific as possible. In acute ischemic stroke, the major therapeutic target in the early phase is often an embolic thrombus occluding a major or minor intracranial artery, thus impeding blood and oxygen supply to the distally located territory. With the advances in CT technology and with the advent of effective reperfusion treatments, basic knowledge about the heterogeneity of thrombus appearance and its associated properties (e.g. lysis resistance) has been accumulated.

First reports in this field specifically addressed the association of location, density properties on non-contrast CT and length with medical reperfusion success following IV tPA administration. During the past ten years, advances in the field of diagnostic and interventional neuroradiology have provided additional stimuli for the progress of this important field of research.

We discuss recent developments in thrombus imaging and their current limitations:

1) Advancements in CT/MR imaging and post-processing techniques have promoted a deeper understanding of thrombus properties. Recently, new methods have proven feasibility of fully automated density measurements[1] and volume estimates[2], thus reducing measurement errors and subjectivity. Moreover, novel imaging characteristics such as quantitative evaluation of contrast penetration into the thrombus (“thrombus perviousness” or “thrombus permeability”) have been proposed[3]. MRI-based thrombus classification using the susceptibility vessel sign was also described by several authors and subcategorized by shape, fragmentation, grade of blooming and quantitative measures of magnetic field inhomogeneity. However, use of some of these techniques is still limited due to lack of accessibility to automated software tools, lack of validation in external data sets, high inter-rater reliability among different definitions of the susceptibility vessel sign, and confusing terminology.

2) The advent of mechanical thrombectomy has created an opportunity to analyze thrombi extracted from cerebral arteries and to correlate particular histological thrombus components with interventional success and etiology. Most studies have found that cardiogenic thrombi are constituted by a larger amount of fibrin/platelet aggregations than do thrombi of other origins. However, there are still conflicting results thus warranting analyses of larger cohorts. Current limitations of this branch of research include a lack of standardized methods for quantification of different thrombus components, uncertainty how to handle analysis of thrombi with multiple fragments (see Figure) and varying nomenclature regarding thrombus components.

Figure: Right, numerous thrombus fragments were extracted in a patient presenting with a large carotid-T thrombus. Left, HE staining of a thrombus fragment, showing the main thrombus components erythrocytes (red and rose areas), the fibrin/thrombocytes aggregations (purple areas) and leucocytes (nucleated cell structures, blue dots) interspersed into each other with no larger organized areas.

Today, thrombus imaging becomes important not only for estimating responsiveness to lytic drugs[4], but also for predicting mechanical reperfusion success and endovascular complications[5]. Importantly, imaging and identification of thrombus characteristics can potentially guide the decision as to which endovascular technique is most likely to succeed in an individual patient. A valuable step towards this direction was recently provided by a post-hoc analysis of ASTER trial data. The authors found that in patients with a susceptibility vessel sign on MRI, higher reperfusion rates were observed if the patients were treated with stent-retriever, as opposed to patients treated with a aspiration first-technique[6].

In summary, and in light of this rapidly growing field of research, it appears almost inevitable that numerous important decisions during the treatment of an acute ischemic stroke patient will implement results derived from thrombus imaging in the near future. These may include estimating the necessity for transferring patients to endovascular treatment capable centers (predicting IV t-PA responsiveness), aiding the selection of endovascular devices, and possibly improving the determination of thrombus origin and secondary prevention. However, before thrombus imaging is ready for clinical practice, there is an unmet need to overcome some of the limitations in this field of research and recently proposed expert recommendations may serve as valuable guidelines[7]. The ultimate goal should be to provide practitioners with models that improve the diagnostic and prognostic accuracy for the above-mentioned decisions. If these issues are addressed appropriately, the last critics will be convinced that we can see what we get.

 

References

  1. Santos EMM, Niessen WJ, Yoo AJ, et al (2016) Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke. PLoS One 11:1–16 . doi: 10.1371/journal.pone.0145641
  2. Mokin M, Morr S, Natarajan SK, et al (2014) Thrombus density predicts successful recanalization with Solitaire stent retriever thrombectomy in acute ischemic stroke. J Neurointerv Surg 7:104–107 . doi: 10.1136/neurintsurg-2013-011017
  3. Santos EMM, Marquering HA, den Blanken MD, et al (2016) Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke. STROKE 47:732–741 . doi: 10.1161/STROKEAHA.115.011187
  4. Menon BK, Al-Ajlan FS, Najm M, et al. Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke. JAMA. 2018;320(10):1017–1026. doi:10.1001/jama.2018.12498.
  5. Heo JH, Kim K, Yoo J, et al (2017) Computed Tomography-Based Thrombus Imaging for the Prediction of Recanalization after Reperfusion Therapy in Stroke. J Stroke 19:40–49 . doi: 10.5853/jos.2016.01522
  6. Bourcier R, Mazighi M, Labreuche J, et al (2018) Susceptibility vessel sign in the ASTER trial: Higher recanalization rate and more favourable clinical outcome after first line stent retriever compared to contact aspiration. J Stroke 20:268–276 . doi: 10.5853/jos.2018.00192
  7. De Meyer SF, Andersson T, Baxter B, et al (2017) Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions. Int J Stroke 12:606–614 . doi: 10.1177/1747493017709671