Water content for clot composition prediction in acute ischemic stroke

PLOS ONE RESEARCH ARTICLE Water content for clot composition prediction in acute ischemic stroke Kenichi Sakuta ID1,2,3, Taichiro Imahori1,4, Amir Molaie ID3, Mahsa Ghovvati1, Neal Rao3, Satoshi Tateshima1, Naoki Kaneko ID1* 1 Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America, 2 Department of Neurology, Jikei University School of Medicine, Tokyo, Japan, 3 Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America, 4 Department of Neurosurgery, Kitaharima Medical Center, Hyogo, Japan * a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Abstract Background OPEN ACCESS Citation: Sakuta K, Imahori T, Molaie A, Ghovvati M, Rao N, Tateshima S, et al. (2024) Water content for clot composition prediction in acute ischemic stroke. PLoS ONE 19(5): e0304520. https://doi. org/10.1371/journal.pone.0304520 Editor: Sonu Bhaskar, Global Health Neurology Lab / NSW Brain Clot Bank, NSW Health Pathology / Liverpool Hospital and South West Sydney Local Health District / Neurovascular Imaging Lab, Clinical Sciences Stream, Ingham Institute, AUSTRALIA Received: January 6, 2024 Accepted: May 14, 2024 Published: May 24, 2024 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0304520 Copyright: © 2024 Sakuta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. Materials and methods This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. Results The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion We identified a significant inverse relationship between clot RBC concentration and water content. Accurate detection of this feature through diagnostic imaging could be beneficial for preoperative clot characterization and planning in MT for AIS. PLOS ONE | https://doi.org/10.1371/journal.pone.0304520 May 24, 2024 1 / 10 PLOS ONE Data Availability Statement: The dataset relevant to this study cannot be shared publicly due to the presence of potentially identifying patient data. We confirm that all non-identifying data underlying the findings are fully available without restriction. All relevant non-identifying data are included within the paper. Funding: This study was funded by Society of Vascular and Interventional Neurology (SVIN) Pilot Grant to IT and NK. The equipment and material purchase were supported by Tarsadia Foundation, Jennifer Carroll Wilson Aneurysm Foundation and Frederick Gardner Cottrell Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Water content and stroke clot composition Introduction Acute ischemic stroke (AIS) is a major cause of fatality and disability around the world [1]. A significant cause of cerebral infarction is large vessel occlusion (LVO), a condition in which major brain arteries are blocked, often leading to severe ischemic strokes. LVOs are associated with high rates of disability and mortality, making them a critical focus in stroke research and treatment [2,3]. Mechanical thrombectomy (MT), a procedure to remove the occluding clot, has become a gold standard treatment for ischemic stroke caused by LVO [4,5]. The most common MT methods involve the use of an aspiration catheter, stent retriever, or a combination of both [6]. While these techniques have demonstrated high rates of successful recanalization [7], achieving successful reperfusion with a single pass–deemed the “first-pass effect”–is associated with improved clinical outcomes and fewer procedure-related complications [8–10]. Clot pathologies play a crucial role in influencing the success of MT and achieving firstpass effect [11,12]. The stent retriever technique, for instance, demonstrates greater efficacy in removing red blood cells (RBC)-rich clots compared to fibrin-rich clots [13–15]. However, very soft RBC clots can be fragmented by the complete opening of the stent retriever [16]. On the other hand, fibrin-rich pathology can reduce the efficacy of stent retrievers, as fibrin-rich clots are not easily penetrated by the stent struts. In contrast, aspiration has demonstrated efficacy in removing very soft clots [16], although it may encounter difficulties with large, delicate clots or moderately stiff ones. A combined approach, harnessing- both an aspiration catheter and stent retriever- might offer a synergistic advantage, potentially elevating treatment efficacy. An in-vitro study showed that the combined technique achieved the highest success rates in removing stiff, calcified clots [17]. Consequently, determining clot pathology prior to MT could be useful for selecting the most effective initial treatment strategy [18–21]. Currently, there are no diagnostic imaging techniques that can reliably and consistently detail clot pathologies. Notably, the process of clot formation within blood vessels is complex and influenced by numerous factors, such as blood composition, the condition of the vessel wall, and blood flow [22,23]. Additionally, clots exhibit heterogeneous pathologie (...truncated)