A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level

Abstract

After introduction of the protoporphyrin IX-triplet state lifetime technique as a new method to measure mitochondrial oxygen tension in vivo, the development of a clinical monitor was started. This monitor is the “COMET”, an acronym for Cellular Oxygen METabolism. The COMET is a non-invasive electrically powered optical device that allows measurements on the skin. The COMET is easy to transport, due to its lightweight and compact size. After 5-aminolevulinic acid application on the human skin, a biocompatible sensor enables detection of PpIX in the mitochondria. PpIX acts as a mitochondrially located oxygen-sensitive dye. Three measurement types are available in the touchscreen-integrated user interface, ‘Single’, ‘Interval’ and ‘Dynamic measurement’. COMET is currently used in several clinical studies in our institution. In this first description of the COMET device we show an incidental finding during neurosurgery. To treat persisting intraoperative hypertension a patient was administered clonidine, but due to rapid administration an initial phase of peripheral vasoconstriction occurred. Microvascular flow and velocity parameters measured with laser-doppler (O2C, LEA Medizintechnik) decreased by 44 and 16% respectively, but not the venous-capillary oxygen saturation. However, mitochondrial oxygen tension in the skin detected by COMET decreased from a steady state of 48 to 16 mmHg along with the decrease in flow and velocity. We conclude that COMET is ready for clinical application and we see the future for this bedside monitor on the intensive care, operating theater, and testing of mitochondrial effect of pharmaceuticals.

NADH Autofluorescence—A Marker on its Way to Boost Bioenergetic Research

“…The idea is that continuous oxygen consumption, for example by active complex IV, results in a lower pO 2 in the close proximity to the complex. Protoporphyrin IX has been shown to be sensitive enough for detecting changes in mitochondrial respiration (82) and the technique has already been applied in clinical studies (83). Besides externally applied phosphorescent sensors, protoporphyrin IX is an endogenous, mitochondrial porphyrin, which exhibits delayed fluorescence.…”

“…Similar to phosphorescence, delayed fluorescence is also quenched by oxygen, enabling the use of protoporphyrin IX as a mitochondrial sensor for oxygen tension (81). Protoporphyrin IX has been shown to be sensitive enough for detecting changes in mitochondrial respiration (82) and the technique has already been applied in clinical studies (83). However, with reference to quantifying respiration in a research setting, a thorough characterization of the influencing factors is still needed, as well as intensive studies on how phosphorescent sensors in the mitochondria could complement NADH imaging.…”

Oxygen‐dependent delayed fluorescence of protoporphyrin IX measured in the stomach and duodenum during upper gastrointestinal endoscopy

“…Since PpIX diffuses slowly out of the mitochondria, it will not solely remain in the mitochondria, making the localization of the signal less specific over time. The COMET system provides the clinical parameter “mitoPO 2 ” (mitochondrial oxygen tension), to distinguish the measurement from, for example, hemoglobin‐based “tissue oxygen” measurements, since such parameters provide other information from different tissue compartments . However, the reader should keep in mind that the origin of the PpIX delayed fluorescence signal is not only mitochondrial and depends on tissue type, and the amount of time after ALA administration.…”

Hemodynamic monitoring in children with heart disease: Overview of newer technologies

“…5‐Aminolaevulinic acid is applied locally or systemically to boost PpIX levels in the mitochondria, after which oxygen sensing is possible. A recent clinical version of the monitor, called COMET (Photonics Healthcare, Utrecht, the Netherlands), is described, along with the details of the technique itself, in Ubbink et al …”