Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of Interest Disclosures: There are no GLPG0187 disclosures.. to other integrins such as v3 and 51. Antibodies against active site IIb3 that bind irrespective of activation state such as abcixamab have been used successfully to image human thrombus in vivo.10 The use of LIBS antibodies is potentially advantageous since they bind to sites exposed only upon integrin activation, thereby selectively attaching to activated platelets and reducing attachment to quiescent circulating platelets.13 Moreover, unlike non-activation-specific antibodies and RGD peptides, LIBS antibodies are less likely to trigger ligation-dependent platelet activation through outside-in signaling.13 The study by Wang et al. demonstrates that microbubbles bearing LIBS antibodies attach to platelets or microthrombi, and enhance thrombi on ultrasound imaging of the murine carotid artery treated with FeCl. There are a few key steps that are needed in determining the impact of this technologic advance. Most importantly, there now needs to be a direct comparison of microbubbles bearing LIBS antibodies to those targeted by either RGD peptides or non-activation-specific antibodies with regards to both microbubble binding efficiency and thrombus enhancement. Also, examining the influence of plasma on microbubble attachment to platelets in the flow chamber in this study would have been helpful for establishing the degree to which plasma proteins such as fibrinogen inhibit attachment of the LIBS-microbubbles under physiologic shear conditions. It is worth noting that the peak signal enhancement that was achieved during in vivo imaging with LIBS-microbubbles was quite low (40% enhancement), substantially lower than that previously GLPG0187 described for contrast ultrasound molecular imaging of the aorta in murine models of atherosclerotic disease where 10-fold enhancement has been achieved.14 It is unlikely that poor targeting efficiency was the primary reason. Instead low enhancement was likely a result of imaging methodology. High frequency (40 MHz), single pulse, fundamental (similar send and receive frequency) GLPG0187 imaging may be ideal for defining thrombus in the murine carotid artery, however it is poorly suited to detecting microbubble signal. Instead low to intermediate frequencies with multi-pulse imaging algorithms that are specifically designed to detect microbuble nonlinear signals are likely to increase signal relative to tissue signal for this agent like it has for most other microbubble agents.15 As with any new molecular imaging technology that is developed and shown to be feasible, a critical question is whether targeted imaging of thrombus provides any unique or incremental value to what is already available to the researcher or clinician. The study by Wang et al. was designed to test feasibility rather than to show incremental value to non-contrast or non-targeted contrast imaging. In other words, we do not know whether contrast ultrasound with LIBS-microbubbles improves the detection of small thrombi or provides greater accuracy for sizing thrombus over time. Although the authors state Hapln1 that thrombus imaging can be used to evaluate thrombolytic efficacy, one can certainly imagine other scenarios where molecular imaging of the platelet component of thrombus could have a positive impact. Targeted imaging may provide a unique opportunity to detect or study microvascular thrombus as a mechanism of no-flow in acute coronary syndromes (ACS). In large vessels, it could potentially detect microthrombi in stable patients or non-culprit vessels which have been correlated with heightened risk for plaque progression.16 In stroke.