Hemoglobin state-flux: A finite-state model representation of the hemoglobin signal for evaluation of the resting state and the influence of disease

SUMMARY: In this report we introduce a weak-model approach for examination of the intrinsic time-varying properties of the hemoglobin signal, with the aim of advancing the application of functional near infrared spectroscopy (fNIRS) for the detection of breast cancer, among other potential uses. The developed methodology integrates concepts from stochastic network theory with known modulatory features of the vascular bed, and in doing so provides access to a previously unrecognized dense feature space that is shown to have promising diagnostic potential. Notable features of the methodology include access to this information solely from measures acquired in the resting state, and analysis of these by treating the various components of the hemoglobin (Hb) signal as a co-varying interacting system. APPROACH: The principal data-transform kernel projects Hb state-space trajectories onto a coordinate system that constitutes a finite-state representation of covariations among the principal elements of the Hb signal (i.e., its oxygenated (ΔoxyHb) and deoxygenated (ΔdeoxyHb) forms and the associated dependent quantities: total hemoglobin (ΔtotalHb = ΔoxyHb + ΔdeoxyHb), hemoglobin oxygen saturation (ΔHbO(2)Sat = 100Δ(oxyHb/totalHb)), and tissue-hemoglobin oxygen exchange (ΔHbO(2)Exc = ΔdeoxyHb—ΔoxyHb)). The resulting ten-state representation treats the evolution of this signal as a one-space, spatiotemporal network that undergoes transitions from one state to another. States of the network are defined by the algebraic signs of the amplitudes of the time-varying components of the Hb signal relative to their temporal mean values. This assignment produces several classes of coefficient arrays, most with a dimension of 10×10. BIOLOGICAL MOTIVATION: Motivating our approach is the understanding that effector mechanisms that modulate blood delivery to tissue operate on macroscopic scales, in a spatially and temporally varying manner. Also recognized is that this behavior is sensitive to nonlinear actions of these effectors, which include the binding properties of hemoglobin. Accessible phenomenology includes measures of the kinetics and probabilities of network dynamics, which we treat as surrogates for the actions of feedback mechanisms that modulate tissue-vascular coupling. FINDINGS: Qualitative and quantitative features of this space, and their potential to serve as markers of disease, have been explored by examining continuous-wave fNIRS 3D tomographic time series obtained from the breasts of women who do and do not have breast cancer. Inspection of the coefficient arrays reveals that they are governed predominantly by first-order rate processes, and that each array class exhibits preferred structure that is mainly independent of the others. Discussed are strategies that may serve to extend evaluation of the accessible feature space and how the character of this information holds potential for development of novel clinical and preclinical uses.