Transit Time Measurement in Indicator Dilution Curves: Overcoming the Missing Ground Truth and Quantifying the Error

The vascular function of a vessel can be qualitatively and intraoperatively checked by recording the blood dynamics inside the vessel via fluorescence angiography (FA). Although FA is the state of the art in proving the existence of blood flow during interventions such as bypass surgery, it still lacks a quantitative blood flow measurement that could decrease the recurrence rate and postsurgical mortality. Previous approaches show that the measured flow has a significant deviation compared to the gold standard reference (ultrasonic flow meter). In order to systematically address the possible sources of error, we investigated the error in transit time measurement of an indicator. Obtaining in vivo indicator dilution curves with a known ground truth is complex and often not possible. Further, the error in transit time measurement should be quantified and reduced. To tackle both issues, we first computed many diverse indicator dilution curves using an in silico simulation of the indicator's flow. Second, we post-processed these curves to mimic measured signals. Finally, we fitted mathematical models (parabola, gamma variate, local density random walk, and mono-exponential model) to re-continualize the obtained discrete indicator dilution curves and calculate the time delay of two analytical functions. This re-continualization showed an increase in the temporal accuracy up to a sub-sample accuracy. Thereby, the Local Density Random Walk (LDRW) model performed best using the cross-correlation of the first derivative of both indicator curves with a cutting of the data at 40% of the peak intensity. The error in frames depends on the noise level and is for a signal-to-noise ratio (SNR) of 20 dB and a sampling rate of fs = 60 Hz at fs-1·0.25(±0.18), so this error is smaller than the distance between two consecutive samples. The accurate determination of the transit time and the quantification of the error allow the calculation of the error propagation onto the flow measurement. Both can assist surgeons as an intraoperative quality check and thereby reduce the recurrence rate and post-surgical mortality.