Targeting Contrast Agents With Peak Near-Infrared-II (NIR-II) Fluorescence Emission for Non-invasive Real-Time Direct Visualization of Thrombosis

Thrombosis within the vasculature arises when pathological factors compromise normal hemostasis. On doing so, arterial thrombosis (AT) and venous thrombosis (VT) can lead to life-threatening cardio-cerebrovascular complications. Unfortunately, the therapeutic window following the onset of AT and VT is insufficient for effective treatment. As such, acute AT is the leading cause of heart attacks and constitutes ∼80% of stroke incidences, while acute VT can lead to fatal therapy complications. Early lesion detection, their accurate identification, and the subsequent appropriate treatment of thrombi can reduce the risk of thrombosis as well as its sequelae. As the success rate of therapy of fresh thrombi is higher than that of old thrombi, detection of the former and accurate identification of lesions as thrombi are of paramount importance. Magnetic resonance imaging, x-ray computed tomography (CT), and ultrasound (US) are the conventional non-invasive imaging modalities used for the detection and identification of AT and VT, but these modalities have the drawback of providing only image-delayed indirect visualization of only late stages of thrombi development. To overcome such limitations, near-infrared (NIR, ca. 700–1,700 nm) fluorescence (NIRF) imaging has been implemented due to its capability of providing non-invasive real-time direct visualization of biological structures and processes. Contrast agents designed for providing real-time direct or indirect visualization of thrombi using NIRF imaging primarily provide peak NIR-I fluorescence emission (ca. 700–1,000 nm), which affords limited tissue penetration depth and suboptimal spatiotemporal resolution. To facilitate the enhancement of the visualization of thrombosis via providing detection of smaller, fresh, and/or deep-seated thrombi in real time, the development of contrast agents with peak NIR-II fluorescence emission (ca. 1000–1,700 nm) has been recently underway. Currently, however, most contrast agents that provide peak NIR-II fluorescence emissions that are purportedly capable of providing direct visualization of thrombi or their resultant occlusions actually afford only the indirect visualization of such because they only provide for the (i) measuring of the surrounding vascular blood flow and/or (ii) simple tracing of the vasculature. These contrast agents do not target thrombi or occlusions. As such, this mini review summarizes the extremely limited number of targeting contrast agents with peak NIR-II fluorescence emission developed for non-invasive real-time direct visualization of thrombosis that have been recently reported.