Abstract
Blood clotting is a serious clinical complication of many medical procedures and disorders including surgery, catheterization, transplantation, extracorporeal circuits, infections, and cancer. This complication leads to high patient morbidity and mortality due to clot-induced pulmonary embolism, stroke, and in some cases heart attack. Despite the clear medical significance, little progress has been made in developing the methods for detection of circulating blood clots (CBCs), also called emboli. We recently demonstrated the application of in vivo photoacoustic (PA) flow cytometry (PAFC) with unfocused ultrasound transducers for detection of CBCs in small vessels in a mouse model. In the current study, we extend applicability of PAFC for detection of CBCs in relatively large (1.5-2 mm) and deep (up to 5-6 mm) blood vessels in rat and rabbit models using a high pulse rate 1064 nm laser and focused ultrasound transducer with a central hole for an optic fiber. Employing phantoms and chemical activation of clotting, we demonstrated PA identification of white, red, and mixed CBCs producing negative, positive, and mixed PA contrast in blood background, respectively. We confirmed that PAFC can detect both red and white CBCs induced by microsurgical procedures, such as a needle or catheter insertion, as well as stroke modeled by injection of artificial clots. Our results show great potential for a PAFC diagnostic platform with a wearable PA fiber probe for diagnosis of thrombosis and embolism in vivo that is impossible with existing techniques.
Highlights
The genesis of circulating blood clot (CBC) formation called emboli usually starts as a response to a blood vessel injury
We demonstrated that in vivo PAFC can detect CBCs triggered by melanoma and microsurgical invasion
When an red blood cells (RBCs)-rich red CBC passes through the irradiated blood volume, a transient increase in the local absorption, which is associated with a high concentration of hemoglobin (Hb), results in a sharp positive PA peak
Summary
The genesis of circulating blood clot (CBC) formation called emboli usually starts as a response to a blood vessel injury. Even in the absence of injury, many diseases and medical procedures may provoke the formation of CBCs that eventually block vessels at different locations [1–9]. Every year in the United States, over 795,000 individuals have a new or recurrent stroke often as a result of non-valvular atrial fibrillation, carotid disease, left ventricular dysfunction, or prosthetic valves. Pulmonary embolism (PE), the third most common cause of hospital-related deaths, occurs as a result of a blood clot from a lowerextremity thromboembolism getting wedged into an artery in the lungs. Thromboembolism (TE) typically occurs in the veins of the extremities, lungs (PE), brain (ischemic stroke), heart (myocardial infarction), kidney (acute renal failure), and the gastrointestinal tract [10–12]. TE is a common complication of infection, inflammation, catheters, transplantation, extracorporeal circuits and surgery, including carotid endarterectomy and coronary artery bypass grafting [12–14]
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