title: Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry.
abstract: 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.
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.|Department of General and Visceral Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Mazen A
authors.initials: MA
authors.lastname: Juratli
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.
authors.forename: Yulian A
authors.initials: YA
authors.lastname: Menyaev
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sarimollaoglu
authors.affiliation: Department of Biostatistics, UAMS, Little Rock, AR, 72205, United States of America.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siegel
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Nedosekin
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, UAMS, Little Rock, AR, 72205, United States of America.
authors.forename: James Y
authors.initials: JY
authors.lastname: Suen
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Moscow Region 141700, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Melerzanov
authors.affiliation: Department of Neurosurgery, University Hospital Dresden, Dresden, Germany.
authors.forename: Tareq A
authors.initials: TA
authors.lastname: Juratli
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.
authors.forename: Ekaterina I
authors.initials: EI
authors.lastname: Galanzha
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, United States of America.|Department of Otolaryngology - Head and Neck Surgery, UAMS, Little Rock, AR, 72205, United States of America.|Moscow Institute of Physics and Technology (MIPT), Moscow Region 141700, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055088:Early Detection of Cancer; D004617:Embolism / Q000097:blood / Q000175:diagnosis*; D005434:Flow Cytometry / Q000379:methods*; D008546:Melanoma, Experimental / Q000097:blood / Q000175:diagnosis*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D061088:Photoacoustic Techniques / Q000379:methods*