In Vivo Transcutaneous Monitoring of Hemoglobin Derivatives Using a Red-Green-Blue Camera-Based Spectral Imaging Technique

Abstract

Cyanosis is a pathological condition that is characterized by a bluish discoloration of the skin or mucous membranes. It may result from a number of medical conditions, including disorders of the respiratory system and central nervous system, cardiovascular diseases, peripheral vascular diseases, deep vein thrombosis, and regional ischemia. Cyanosis can also be elicited from methemoglobin. Therefore, a simple, rapid, and simultaneous monitoring of changes in oxygenated hemoglobin and deoxygenated hemoglobin is useful for protective strategies against organ ischemic injury. We previously developed a red-green-blue camera-based spectral imaging method for the measurements of melanin concentration, oxygenated hemoglobin concentration (C_HbO), deoxygenated hemoglobin concentration (C_HbR), total hemoglobin concentration (C_HbT) and tissue oxygen saturation (StO₂) in skin tissues. We leveraged this approach in this study and extended it to the simultaneous quantifications of methemoglobin concentration (C_metHb), C_HbO, C_HbR, and StO₂. The aim of the study was to confirm the feasibility of the method to monitor C_metHb, C_HbO, C_HbR, C_HbT, and StO₂. We performed in vivo experiments using rat dorsal skin during methemoglobinemia induced by the administration of sodium nitrite (NaNO₂) and changing the fraction of inspired oxygen (FiO₂), including normoxia, hypoxia, and anoxia. Spectral diffuse reflectance images were estimated from an RGB image by the Wiener estimation method. Multiple regression analysis based on Monte Carlo simulations of light transport was used to estimate C_HbO, C_HbR, C_metHb, C_HbT, and StO₂. C_metHb rapidly increased with a half-maximum time of less than 30 min and reached maximal values nearly 60 min after the administration of NaNO₂, whereas StO₂ dramatically dropped after the administration of NaNO₂, indicating the temporary production of methemoglobin and severe hypoxemia during methemoglobinemia. Time courses of C_HbT and StO₂, while changing the FiO₂, coincided with well-known physiological responses to hyperoxia, normoxia, and hypoxia. The results indicated the potential of this method to evaluate changes in skin hemodynamics due to loss of tissue viability and vitality.

Keywords: Monte Carlo simulation; deoxygenated hemoglobin; methemoglobin; multiple regression analysis; oxygenated hemoglobin; spectral imaging; tissue oxygen saturation; wiener estimation method.