Abstract

Microvasculature hemoglobin oxygen saturation (SaO2) is important in the progression of various pathologies. Non-invasive depth-resolved measurement of SaO2 levels in tissue microvasculature has the potential to provide early biomarkers and a better understanding of the pathophysiological processes allowing improved diagnostics and prediction of disease progression. We report proof-of-concept in vivo depth-resolved measurement of SaO2 levels in selected 30 µm diameter arterioles in the murine brain using Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) with 800 nm and 770 nm photothermal excitation wavelengths. Depth location of back-reflected light from a target arteriole was confirmed using Doppler and speckle contrast OCT images. SaO2 measured in a murine arteriole with DWP-OCT is linearly correlated (R2=0.98) with systemic SaO2 values recorded by a pulse-oximeter. DWP-OCT are steadily lower (10.1%) than systemic SaO2 values except during pure oxygen breathing. DWP-OCT is insensitive to OCT intensity variations and is a candidate approach for in vivo depth-resolved quantitative imaging of microvascular SaO2 levels.

Highlights

  • Depth-resolved in vivo quantification of hemoglobin oxygen saturation (SaO2) in tissue microvasculature can advance the understanding, monitoring and prediction of the progression of a number of malignant, inflammatory, ischaemic, infectious and immune diseases including cancer, stroke, diabetic retinopathy, glaucoma, atherosclerosis, and vascular dementia [1,2]

  • We extend Dual-Wavelength Photothermal (DWP)-Optical Coherence Tomography (OCT) to depth-resolved in vivo measurement of SaO2 levels in microvessels in a murine animal model

  • The experimental setup for our DWP-OCT system (Fig. 1) to measure SaO2 levels contains two major components: a) photothermal excitation lasers at 800 nm and 770 nm to induce nanometer-scale optical pathlength changes in murine tissue; and b) a Phase Sensitive (PhS) OCT system [37] to measure SaO2-dependent op changes induced by photothermal excitation laser light

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Summary

Introduction

Depth-resolved in vivo quantification of hemoglobin oxygen saturation (SaO2) in tissue microvasculature can advance the understanding, monitoring and prediction of the progression of a number of malignant, inflammatory, ischaemic, infectious and immune diseases including cancer, stroke, diabetic retinopathy, glaucoma, atherosclerosis, and vascular dementia [1,2]. Detection and longitudinal study of pathologies that involve angiogenesis are of great interest to clinical investigators and biomedical engineers. A number of approaches have been developed to assess microvascular oxygen saturation with varying levels of spatial and temporal resolution. Microvascular oxygenation profiles can be measured using an oxygen-sensitive microelectrode [3,4,5,6,7]. Oxygen-sensitive microelectrodes have high spatial resolution (10 μm) and can provide oxygen saturation in a selected tissue layer, the micro-environment is irreversibly disturbed, the measurement is onedimensional and cannot be translated to humans. Magnetic resonance imaging (MRI) has been used to investigate relative and absolute tissue oxygenation with depth resolution and a large

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