Vascular-centric mapping of in vivo blood oxygen saturation in preclinical models.

Assessing intravascular blood oxygen saturation (SO) is crucial for characterizing in vivo microenvironmental changes in preclinical models of injury and disease. However, most conventional optical imaging techniques for mapping in vivo SO assume or compute a single value of the optical path-length in tissue. This is especially detrimental when mapping in vivo SO in experimental disease or wound healing models that are characterized by vascular and tissue remodeling. Therefore, to circumvent this limitation we developed an in vivo SO mapping technique that utilizes hemoglobin-based intrinsic optical signal (IOS) imaging combined with a vascular-centric estimation of optical path-lengths. In vivo arterial and venous SO distributions derived with this approach closely matched those reported in the literature, while those derived using the single path-length (i.e. conventional) approach did not. Moreover, in vivo cerebrovascular SO strongly correlated (R > 0.7) with changes in systemic SO measured with a pulse oximeter during hypoxia and hyperoxia paradigms. Finally, in a calvarial bone healing model, in vivo SO assessed over four weeks was spatiotemporally correlated with angiogenesis and osteogenesis (R > 0.6). During the early stages of bone healing (i.e. day 10), angiogenic vessels surrounding the calvarial defect exhibited mean SO that was elevated by10 % (p < 0.05) relative to that observed at a later stage (i.e., day 26), indicative of their role in osteogenesis. These correlations were not evident with the conventional SO mapping approach. The feasibility of our wide field-of-view in vivo SO mapping approach illustrates its potential for characterizing the microvascular environment in applications ranging from tissue engineering to cancer.