Development and Validation of a Continuous Real-Time Optical Sensor for Indocyanine Green Clearance Measurement During Ex-Vivo Perfusion of Human Livers

Derwent, E. N. J.; Risbey, C. W. G.; Niu, A.; Yousif, P.; Fonseka, N.; Curry, S.; Seow, C.; Ng, I.; McCaughan, G. W.; Crawford, M.; Pulitano, C.; Babekuhl, D.

doi:10.1101/2025.11.05.686646

bioRxiv · 10.1101/2025.11.05.686646

Development and Validation of a Continuous Real-Time Optical Sensor for Indocyanine Green Clearance Measurement During Ex-Vivo Perfusion of Human Livers

Derwent, E. N. J.·Risbey, C. W. G.·Niu, A.·Yousif, P.·Fonseka, N.·Curry, S.·Seow, C.·Ng, I.·McCaughan, G. W.·Crawford, M.·Pulitano, C.·Babekuhl, D.

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Abstract

Liver transplantation remains the only curative treatment for end-stage liver failure, yet its impact is constrained by organ shortages and graft non-utilisation. Machine perfusion (MP) enables ex-vivo assessment of donated livers; however, existing viability criteria rely on intermittent sampling, reducing temporal resolution and accuracy. Indocyanine green (ICG), a clinically validated dye cleared exclusively by hepatocytes, provides a continuous index of hepatic function beyond initial injury. Accordingly, we present a non-invasive, clamp-on optical sensor that enables continuous, real-time quantification of ICG clearance during MP. The sensor consists of a clamp-on module with an 808nm laser and phototransistor connected to a microcontroller-based unit and computer for real-time plotting. The raw phototransistor signal was linearised to a unitless absorbance signal proportional to perfusate ICG; bi-exponential fitting yielded plasma disappearance rate (PDRbi, %/min) and the 15-minute residual fraction (R15). Across 10 whole and 3 split human livers (45 boluses; 13 paired with spectrophotometry), the sensor closely matched spectrophotometric measurements (mean R2 = 0.994; range 0.983-0.999). The sensor resolved expected physiological trends: ICG clearance increased with temperature (PDRbi: 8.2%/min (subnormothermic MP) to 22.6%/min (normothermic MP) (n=4); 9.3%/min (32{degrees}C) to 11.9%/min (36{degrees}C) (n=1)). The sensors continuous signal traces also revealed early mixing dynamics and medication-related effects that are missed by intermittent sampling. This optical sensor enables accurate, real-time monitoring of ICG clearance during ex-vivo perfusion. The ex-vivo setting is uniquely positioned to validate ICG clearance models and enhance clinical interpretation.

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Derwent, E. N. J., Risbey, C. W. G., Niu, A., Yousif, P., Fonseka, N., Curry, S., Seow, C., Ng, I., McCaughan, G. W., Crawford, M., Pulitano, C., Babekuhl, D.. 2025-11-06. Development and Validation of a Continuous Real-Time Optical Sensor for Indocyanine Green Clearance Measurement During Ex-Vivo Perfusion of Human Livers. https://doi.org/10.1101/2025.11.05.686646

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