Optical density based quantification of total haemoglobin concentrations with spectroscopic optical coherence tomography

Spectroscopic optical coherence tomography (sOCT) has emerged as a new possibility for non-invasive quantification of total haemoglobin concentrations [tHb]. Recently, we demonstrated that [tHb] measured in ex-vivo human whole-blood with a conventional sOCT system achieves a precision of 9.10 g/dL with a bias of 1.50 g/dL. This precision improved by acquiring data with a combination of focus tracking and zero-delay acquisition (FZA) that compensated for experimental limitations, increasing to 3.80 g/dL with a bias of 1.50 g/dL. Nevertheless, sOCT precision should improve at least to [Formula: see text] g/dL to be clinically relevant. Therefore, sOCT-based [tHb] determinations require the development of new analysis methods that reduce the variability of [tHb] estimations. In this work, we aim to increase sOCT precision by retrieving the [tHb] content from a numerical optimisation of the optical density (OD), while considering the blood absorption flattening effect. The OD-based approach simplifies previous two-step Lambert–Beer fitting approaches to a single step, thereby reducing errors during the fitting procedure. We validated our model with ex-vivo [tHb] measurements on flowing whole-blood samples in the clinical range (7–23 g/dL). Our results show that, with the new model, conventional sOCT can determine [tHb] with a precision of 3.09 g/dL and a bias of 0.86 g/dL compared to a commercial blood analyser. We present further precision improvement by combining the OD methodology with FZA, leading to a precision of 2.08 g/dL with a bias of 0.46 g/dL.