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Recent near-infrared approaches to cytochrome-c-oxidase monitoring: a systematic review of instruments and algorithms

Robert Ward, Mamadou Diop, Ilias Tachtsidis, Felipe Orihuela‐Espina

Physics in Medicine and Biology, 2026

Abstract

Abstract Broadband near-infrared spectroscopy (bNIRS) has emerged as a promising technique for non-invasive monitoring of the redox state of cytochrome-c-oxidase (CCO), a key enzyme in cellular energy production. While early work focused on linear approaches based on the modified Beer–Lambert law (MBLL), recent decades have seen substantial diversification in both instrumentation and computational strategies. To capture this evolution, we conducted a systematic review following preferred reporting items for systematic reviews and meta-analyses guidelines across PubMed, Web of Science, ScienceDirect (limited to the journal NeuroImage ), and IEEE Xplore, identifying 35 studies that reported novel hardware or algorithmic approaches to CCO reconstruction. Hardware developments ranged from broadband lamps and supercontinuum lasers to light emitting diode and complementary metal-oxide-semiconductor-based miniaturised systems, reflecting a trade-off between spectral coverage, portability, and sensitivity. Algorithmic innovations encompassed refinements of MBLL, diffusion theory, stochastic Monte Carlo modelling, and emerging machine learning methods, each addressing challenges of scattering, spectral overlap, and low signal-to-noise. Despite progress, the field remains limited by variability in instrumentation, standardised validation protocols, and the inherent weakness of the CCO signal relative to haemoglobin. We conclude that advancing bNIRS toward robust, clinically relevant…

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Evidence Hub reads this as a systematic review, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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