Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry
Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry
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DOI：
10.1371/journal.pone.0156269
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发表时间：
2016-05-26
期刊：
影响因子：
3.7
通讯作者：
Zharov, Vladimir P.
中科院分区：
文献类型：
--
作者：
Juratli, Mazen A.;Menyaev, Yulian A.;Zharov, Vladimir P.
血栓栓塞事件是世界上导致患者死亡的主要原因之一。栓子或凝块形成有多种病因，包括副肿瘤、手术后、烧灼、移植或体外循环。尽管具有医学意义，但早期栓塞检测、筛查和控制方面进展甚微。我们研究的目的是测试体内光声（PA）流式细胞术（PAFC）技术在非侵入性实时栓塞检测中的实用性。使用体内 PAFC，对两种不同小鼠模型的血流中的栓塞进行非侵入性监测。无肿瘤小鼠模型由两组组成，一组是夹住四肢以产生血管瘀滞（7次手术），另一组是接受手术（7次手术）。携带黑色素瘤的小鼠模型也由两组组成，一组对植入的肿瘤进行压缩（8 次手术），另一组对植入的肿瘤进行手术切除（8 次手术）。我们证明 PAFC 可以检测单个栓子，并且能够区分小血管中富含红细胞（红色）和富含白细胞/血小板（白色）的栓子。我们发现，与无肿瘤小鼠相比，荷瘤小鼠的循环栓塞水平有所增加（p = 0.0013）。在血管停滞期间（p = 0.033）和手术切除后（符号秩 p = 0.031），无肿瘤对照小鼠的循环栓塞数量暂时增加。在肿瘤压缩期间（p = 0.013）和肿瘤切除后（p = 0.012）也发现了类似的观察结果。首次可以非侵入性地检测体内未标记的栓子，并确认循环栓子中是否存在色素肿瘤细胞。对癌症进展和医疗过程中栓子动态的深入了解凸显了 PAFC 在早期检测癌症和手术引起的栓子方面的临床潜力，以通过适时治疗预防致命的血栓栓塞并发症。
Thromboembolic events are one of the world's leading causes of death among patients. Embolus or clot formations have several etiologies including paraneoplastic, post-surgery, cauterization, transplantation, or extracorporeal circuits. Despite its medical significance, little progress has been made in early embolus detection, screening and control. The aim of our study is to test the utility of the in vivo photoacoustic (PA) flow cytometry (PAFC) technique for non-invasive embolus detection in real-time. Using in vivo PAFC, emboli were non-invasively monitored in the bloodstream of two different mouse models. The tumor-free mouse model consisted of two groups, one in which the limbs were clamped to produce vessel stasis (7 procedures), and one where the mice underwent surgery (7 procedures). The melanoma-bearing mouse model also consisted of two groups, one in which the implanted tumor underwent compression (8 procedures), and one where a surgical excision of the implanted tumor was performed (8 procedures). We demonstrated that the PAFC can detect a single embolus, and has the ability to distinguish between erythrocyte-rich (red) and leukocyte/platelet-rich (white) emboli in small vessels. We show that, in tumor-bearing mice, the level of circulating emboli was increased compared to tumor-free mice (p = 0.0013). The number of circulating emboli temporarily increased in the tumor-free control mice during vessel stasis (p = 0.033) and after surgical excisions (signed-rank p = 0.031). Similar observations were noted during tumor compression (p = 0.013) and after tumor excisions (p = 0.012). For the first time, it was possible to detect unlabeled emboli in vivo non-invasively, and to confirm the presence of pigmented tumor cells within circulating emboli. The insight on embolus dynamics during cancer progression and medical procedures highlight the clinical potential of PAFC for early detection of cancer and surgery-induced emboli to prevent the fatal thromboembolic complications by well-timed therapy.