Measurements of oxygen in tissues: overview and perspectives on methods.
ABSTRACT The goal of this manuscript is to provide a summary of the major techniques that currently are being applied to measure oxygenation of tissues in vivo. Oxygen is one of the key components of metabolism. Oxygen is also a major variable in many diseases, both with respect to the pathophysiological processes and influencing the efficacy of treatment. Unfortunately, however, the measurement of tissue oxygenation is non-trivial. Consequently many different methods have been developed to try to make this measurement. This paper presents a summary, largely in tabular form, of most of the current methods for assessing tissue oxygenation. The table attempts to cover the most pertinent aspects of the techniques and their applications, including their potential niche, limitations, and advantages. Citations are given for each method to point the reader in the direction of relevant literature.
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ABSTRACT: Stereotactic body radiation therapy (SBRT) is a new therapeutic paradigm for treating localized tumors outside of the central nervous system and involves delivering very high doses of focused radiation using unique beam arrangements and special immobilization equipment. It has also been shown recently that many prostate cancers may be better controlled using large dose per fraction treatments such as might be delivered by SBRT. While large dose per fraction treatments are facilitated by new generation radiation delivery equipment, technology cannot independently overcome normal tissue consequences to tubular organs adjacent or within targets (e.g., the urethra and rectum for prostate cancer). As such, careful prospective clinical trials must be designed that appropriate bridge the information learned from laboratory testing, historical clinical experience, and the clinical experience with SBRT from other sites in order to test this new therapy for prostate cancer. Our goal is ultimately to carry out a prospective phase I/II trial of SBRT for treatment of localized prostate cancer such that its true efficacy and toxicity might be characterized. The objective of this application is to establish the collaborations necessary for formulating these protocols, write the protocols, assemble the clinical research infrastructure necessary for submitting the protocols, set up mechanisms for multi-center participation with our center acting as the coordinating center, recruiting, enrolling, treating and following patients, and to support the research infrastructure and clinical researchers performing these tasks.
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ABSTRACT: The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) has been recently introduced as the first method to measure mitochondrial oxygen tension (mitoPo2) in living cells and tissues. The current implementation of the technique is based on oxygen-dependent quenching of the delayed fluorescence lifetime of 5-aminolevulinic-acid-enhanced mitochondrial PpIX. It represents a significant step forward in our ability to comprehensively measure tissue oxygenation. PpIX-TSLT is feasible for application in humans and recently we have been able to measure for the first time mitoPo2 in humans. MitoPo2 in intact tissues reflects the balance between oxygen supply and demand at the cellular level. Administration of aminolevulinic acid induces measurable mitochondrial levels of PpIX. PpIX acts as a mitochondrially located oxygen-sensitive dye by emitting a red delayed fluorescence after excitation with a pulse of green light. The lifetime of the delayed fluorescence is inversely related to Po2 by the Stern-Volmer equation. In vivo measurements of mitoPo2 in liver, heart, and skin of rats have revealed surprisingly high values of typically several tens of mm Hg. Clinical measurements of mitoPo2 are possible as demonstrated by cutaneous measurements in healthy volunteers. Applications of PpIX-TSLT in anesthesiology and intensive care medicine might, e.g., be monitoring mitoPo2 as a resuscitation end point, targeting oxygen homeostasis in the critically ill, and assessing mitochondrial function at the bedside. PpIX-TSLT likely also has applications in other fields also, e.g., providing an oxygen-related feedback signal in photodynamic therapy of malignant tumors.Anesthesia and analgesia 04/2013; 117(4). DOI:10.1213/ANE.0b013e31828f29da · 3.42 Impact Factor
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ABSTRACT: This thesis describes the implementation of novel approaches for measuring tissue oxygenation based on oxygen-dependent quenching of the triplet-state lifetime of porphyrins. Ultimately we created a tool for assessment of mitochondrial oxygen tension in vivo. The first measurements indicate much higher mitoPO2 values than generally expected. These findings come in an era of new insights in cellular oxygen sensing and oxygen-dependence of gene expression and metabolism. The described methods are expected to be a valuable addition to the arsenal of tools available to scientist for unraveling the mechanisms of oxygen delivery and consumption under various pathophysiological circumstances. Oxygen is again important, as it has always been …