# Discrete Wavelength Frequency Domain Near Infrared Spectroscopy for Non-Invasive Measurement of Cytochrome Oxidation State

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $576,122

## Abstract

PROJECT SUMMARY / ABSTRACT (DESCRIPTION)
Four of the top 10 worldwide causes of death are related to oxygen supply:demand mismatching,(2) and two
involve infectious processes(2) which are known to impact the mitochondria,(27) the oxygen-producing
organelles which generate the majority of ATP in mammals. Despite the essential function of oxidative
phosphorylation (OXPHOS) in human survival,(28) and the disruption of OXPHOS that occurs in a variety of
disease states, our understanding of the exact process of hypoxic cell death remains incompletely
understood.(28-30) This proposal’s objective is to construct and experimentally validate a frequency-domain
near infrared spectroscopy (NIRS) instrument capable of measuring absolute concentrations of oxidized and
reduced forms of cytochrome aa3, the terminal component of the electron transport chain (ETC). Our long
term goal is to develop a patient monitor capable of detecting organ ischemia at the level of the mitochondria
(ETC dysfunction) to facilitate prevention and treatment of leading causes of death. Our central hypothesis is
that combination of emerging advances in engineering, in particular the use of advanced photon detectors (e.g.
silicon photomultipliers [SiPM]) as well as novel combinations of near infrared radiation (NIR) wavelengths, will
allow for accurate measurement of CytOX. We will test our central hypothesis and achieve our objective via the
following specific aims: Specific Aim 1: Select Wavelength Number and Frequency. Using in silico simulation,
we will test all possible combinations of commercially available wavelengths of lasers that can be modulated at
100 MHz to determine the combinations which offer the most attractive tradeoff between accuracy (CytOX
validated against broadband) and simplicity (least number of wavelengths), using a pre-existing dataset;
Specific Aim 2: Optimize Photon Detection. In a laboratory environment, we will test combinations of near
infrared laser light and extended range photomultiplier tubes to identify a combination suitable for frequency
domain spectroscopy measurement of CytOX (the oxidation state of cytochrome aa3); Specific Aim 3: Construct
and Test a Functioning FD-NIRS Device to Measure CytOX. We will construct and test a frequency domain
instrument capable of measuring absolute concentrations of hemoglobin (oxygenated, de-oxygenated) and
cytochrome aa3 (oxidized, reduced) in a quasi-biological tissue phantom.

## Key facts

- **NIH application ID:** 10272895
- **Project number:** 1R21EB031780-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Robert H Thiele
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $576,122
- **Award type:** 1
- **Project period:** 2021-09-21 → 2024-09-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10272895

## Citation

> US National Institutes of Health, RePORTER application 10272895, Discrete Wavelength Frequency Domain Near Infrared Spectroscopy for Non-Invasive Measurement of Cytochrome Oxidation State (1R21EB031780-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10272895. Licensed CC0.

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