Abstract. Recent evidence has suggested that the presence and proliferation of vasa vasorum (VV) in the plaque is correlated to an increase in plaque inflammation and destabilization, leading to acute coronary events (e.g., heart attacks). Therefore, the detection and quantification of VV in plaque (i.e., extra luminal blood perfusion) is an important problem since it may enable the development of an index of plaque vulnerability. In this paper, we explore the feasibility of a method that employs a physics-based model of the scattered intravascular ultrasound (IVUS) radio frequency signal for the detection of blood. We evaluate our method using synthetic data and validate it using six 40 MHz pullback sequences acquired with three different IVUS systems from different arteries of rabbits and swines. Our experimental results are very promising and indicate the feasibility of our method for the computation of a feature that leads to automatic extra-luminal blood detection which may be an indication of plaque inflammation.