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Peer-reviewedCC BY 4.0Physics in Medicine and Biology

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

6 affiliations
  1. 1Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, United States of America
  2. 2Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
  3. 3Lawson Research Institute, St. Joseph’s Health Care, London, ON N6A 4V2, Canada
  4. 4Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States of America
  5. 5Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60607, United States of America
  6. 6Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States of America

Abstract

Objective. 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. Approach. 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, piecewise cubic Hermite interpolation, and gamma-variate interpolation alone. Main results. The combined method completed all 60 patient-by-clipping analyses and produced lower first-pass peak, normalized mean squared error (NMSE), 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 = 1.25–60 ± 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. Significance. 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.

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BibTeX
@article{vavrek2026correction,
  title = {{Correction of arterial input-function saturation for extraction fraction estimation in retinal fluorescein videoangiography}},
  author = {Sarah R Vavrek and Elif Kayaalp Nalbant and Nicholas Konopek and Nicole L Decker and Amani A Fawzi and William F Mieler and Jennifer J Kang-Mieler and Kenneth M Tichauer},
  journal = {Physics in Medicine and Biology},
  year = {2026},
  month = oct,
  doi = {10.1088/1361-6560/aeb793},
  url = {https://doi.org/10.1088/1361-6560/aeb793},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Correction of arterial input-function saturation for extraction fraction estimation in retinal fluorescein videoangiography
AU  - Sarah R Vavrek
AU  - Elif Kayaalp Nalbant
AU  - Nicholas Konopek
AU  - Nicole L Decker
AU  - Amani A Fawzi
AU  - William F Mieler
AU  - Jennifer J Kang-Mieler
AU  - Kenneth M Tichauer
PY  - 2026
DA  - 2026/10/30
JO  - Physics in Medicine and Biology
DO  - 10.1088/1361-6560/aeb793
UR  - https://doi.org/10.1088/1361-6560/aeb793
AB  - Objective. 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. Approach. 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, piecewise cubic Hermite interpolation, and gamma-variate interpolation alone. Main results. The combined method completed all 60 patient-by-clipping analyses and produced lower first-pass peak, normalized mean squared error (NMSE), 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 = 1.25–60 ± 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. Significance. 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.
SN  - 0031-9155
SN  - 1361-6560
ER  -