Correction of arterial input-function saturation for extraction fraction estimation in retinal fluorescein...

Quantitative retinal fluorescein videoangiography (FVA) can estimate extraction fraction (E), but the 8-bit intensity resolution of clinical systems creates a dynamic-range tradeoff: preserving arterial input function (AIF) linearity can restrict tissue signal, particularly for pixel-level analysis. We developed a single-bolus correction method to broaden the usable acquisition range while maintaining E estimation accuracy.

The method combined truncated-mean reconstruction when sufficient unsaturated arterial pixels remained with gamma-variate interpolation when saturation dominated the first-pass peak. Development simulations used four human-derived AIF templates, empirically characterized signal-dependent noise, and 20 paired realizations evaluated over arterial scaling factors f = 0.1-2.25. Tissue curves were generated using a distributed-transit-time AATH model and fitted using a plug-flow AATH model. The locked correction threshold was then evaluated by artificially clipping raw arterial-pixel time curves from 10 originally undersaturated FVAs without adding synthetic noise. Performance was compared with the clipped arterial mean, PCHIP, and gamma-variate interpolation alone.

The combined method completed all 60 patient-by-clipping analyses and produced lower first-pass peak, normalized mean squared error, and area-under-the-curve errors than the comparator methods under moderate-to-strong clipping. In kinetic simulations, mean absolute relative ROI E error with the uncorrected AIF increased from 17 ± 9% at f = 1.25 to 60 ± 20% at f = 2.25, whereas corrected-AIF error remained approximately 10-20%. Single-pixel E error decreased as signal approached the detector ceiling, reached 17 ± 11% at f = 1.75, and remained statistically similar across f = 0.8-2.0. No single-pixel fits failed at f ≥ 1.0.

The correction framework converts modest AIF saturation from a restrictive acquisition limit into a manageable analytical condition. This broader operating range is valuable for 8-bit FVA, supporting acquisition near the detector ceiling to improve tissue signal and enable high-resolution E mapping without dual-bolus acquisition.