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

Abstract

Assessing intravascular blood oxygen saturation (SO₂) 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 SO₂ assume or compute a single value of the optical path-length in tissue. This is especially detrimental when mapping in vivo SO₂ 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 SO₂ 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 SO₂ 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 SO₂ strongly correlated (R² > 0.7) with changes in systemic SO₂ measured with a pulse oximeter during hypoxia and hyperoxia paradigms. Finally, in a calvarial bone healing model, in vivo SO₂ assessed over four weeks was spatiotemporally correlated with angiogenesis and osteogenesis (R² > 0.6). During the early stages of bone healing (i.e. day 10), angiogenic vessels surrounding the calvarial defect exhibited mean SO₂ 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 SO₂ mapping approach. The feasibility of our wide field-of-view in vivo SO₂ mapping approach illustrates its potential for characterizing the microvascular environment in applications ranging from tissue engineering to cancer.

Keywords: Angiogenesis; Imaging; Osteogenesis; Oxygen saturation; Wound healing.