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In neonatal jaundice there is need for the repeated determination of plasma bilirubin to check the indication for, or the efficacy of, phototherapy (Maisels et al., 2012; Maisels & Newman, 2012). Standard method is the invasive measurement, depending on a painful needlestick. So far, the methods available for the non-invasive estimation of plasma bilirubin, i.e. visual assessment of jaundice (Riskin et al., 2008) or the extent of cephalocaudal jaundice progression (Keren et al., 2009), spectral reflectance analysis measuring transcutaneous bilirubin (Bhutani et al., 2000; Ho et al., 2006; Penhaker et al., 2013), or both (Mishra et al., 2009), may help identify those neonates requiring phototherapy but are too inaccurate or of no proven value for this indication in extremely premature neonates, or for monitoring patients undergoing phototherapy or thereafter (Nagar et al., 2013). Noninvasive detection of bilirubin using pulsatile light absorption is similar to our concept but needs intraindividual calibration with 'true' plasma bilirubin (McEwen et al., 2006).
Problem Definition
There is need for a non-invasive method of plasma bilirubin determination with an accuracy similar to pulse oximetry, the non-invasive spectrophotometric measurement of the ratio of oxygenated and total hemoglobin (= oxygen saturation) that has become a routine procedure (Hutton & Fletcher, 1994; Jubran, 1999; Ross et al., 2014; Zijlstra, 1991). However, our application does not target the molar ratio of two metabolites that is independent of the length of the light pathway (length of pathway mathematically cancelling out) (Hutton & Fletcher, 1994; Zijlstra, 1991) but rather the absolute metabolite plasma concentration. But, measuring the length of the light pathway is a technical challenge and obviated at best.
Aim of the Study
We delineate a concept for the non-invasive spectrophotometric determination of absolute plasma bilirubin concentration without the need to measure the length of the light pathway. The method should be both feasible and accurate enough for the application on jaundiced premature or mature neonates to guide phototherapy.
Methods And Results
Basic Assumptions
Arteries show some pulse synchronous fluctuation in diameter. In in-vivo spectrophotometry this results in a fluctuating length of the light-pathway (furtheron referenced to as “pathlength”) and hence -- if light of an appropriate wavelength is used -- in a metabolite-specific pulsatile signal. Isolating the pulsatile signal component from the total light signal detected allows for the determination of the arterial metabolite concentration, provided the corresponding pathlength is known.