Currently, there are no reliable non-invasive methods for monitoring the severity of in-vivo cyanide (CN) toxicity and concurrent physiological changes. Broadband diffuse optical spectroscopy (DOS) is theoretically an ideal diagnostic technique to monitor a range of pathologic conditions. DOS allows quantitative analysis of tissue chromophore concentrations such as oxyhemoglobin, deoxyhemoglobin, methemoglobin, water, and lipid. We developed an in-vivo broadband DOS prototype system that combines multi-frequency domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to accurately measure bulk tissue absorption and scattering spectra between 600 nm and 1000 nm. In this study the DOS prototype was used to monitor cyanide toxicity by quantifying the redox state changes of cytochrome-c oxidase, (since the redox state of cytochrome-c has a distinguishable absorption spectrum) in an animal model to test the feasibility of this concept.
New Zealand White rabbits (NZW) were used in this study. The DOS prototype probe was placed on the inner thigh muscle of the hind leg. After Sodium Cyanide solution of 2mg increments were injected into ear venous line, the systemic blood pressure, arterial, and venous blood gases were monitored. Blood samples were taken to assess the blood cyanide level.
Broadband DOS measurements of tissue hemoglobin (Hb), Oxyhemoglobin (HbO2), water, and, cytochrome c oxidase redox state changes are shown in the below figures. In Figure (a), the reduced state of cytochrome-c increased after CN was injected. In Fig. (b), the changes in cytochrome-c redox state correlated with increasing doses of injected CN.
Broadband DOS has far greater spectral capacity compared to current non-invasive optical spectroscopic modalities. We have demonstrated the feasibility of broadband DOS in-vivo as a monitoring technique for cyanide toxicity using its full spectral capacity and distinct absorption spectrum of cytochrome c oxidase redox state difference.
Non-invasive in vivo monitoring capability of broadband DOS may be a useful advance for monitoring not only in cyanide toxicity but also mitochondrial diseases associated with cytochrome oxidase functions.
J. Armstrong, None.