Real-time prediction of heparin concentration in blood extracorporeal circulation by relaxation time distribution (RTD)
Abstract
In blood extracorporeal circulations such as hemodialysis (HD) and extracorporeal membrane artificial lung (ECMO) during the surgical operation[22], the real-time and noninvasive prediction of heparin concentration c is necessary over the surgical operation time t because thrombus formation should be prevented due to the sudden decrease of c caused by renal metabolism and because bleeding and thrombocytopenia should be prevented due to the sudden increase of c caused by overdosage. In the real clinic, conventionally, c is indirectly predicted by activated clotting time (ACT) which needs blood sampling and coagulation activator mixing to measure the clotting time correlated with c [25]. Because ACT is not capable of real-time prediction of c due to the sampling requirement, heparin with excessive c is normally administered[4], [19]. As real-time prediction of c in previous research, the photoacoustic imaging with nano-second laser pulses and methylene blue as a contrast agent is available because the photoacoustic imaging combines the high contrast of optical imaging with the ultrasound[24]. Although the photoacoustic imaging reveals an increase in the photoacoustic signal caused by the binding of heparin and methylene blue, the photoacoustic imaging is an invasive prediction with methylene blue which has a high risk of side effects [6].
As a real-time and noninvasive prediction of “blood properties” such as cell aggregation, cell membrane shape, and cell and macromolecule concentration, electrical impedance spectroscopy (EIS) measures complex dielectric spectra of red blood cells (RBCs)[2], leukocytes [17], platelets (Egger and Donath, 1995), plasma macromolecules such as bovine serum albumin (BSA) [12] and lysozyme [3], and bound water molecules [27]. The complex dielectric spectra of whole blood (WB) identify the coagulant blood properties and propose the optimal single frequency of the dielectric response for thrombus formation prediction in real-time [2]. However, it is difficult to reveal “heparin properties” in blood by the complex dielectric spectra of WB because the complex dielectric spectra of blood cells and plasma macromolecules are overlapped with similar m-th. Fig. 1 shows the schematic of m-th relaxation frequencies fm implementing in EIS of tissues.