Diabetes markedly raises the risk of microvascular and macrovascular diseases, major contributors to higher morbidity and mortality in this increasingly prevalent disorder. The resulting poor tissue oxygenation due to compromised circulation accounts for the poor healing, infection, and deterioration of foot ulcers in diabetics; this is the basic underlying pathophysiological factor. In current clinical practice, there is no technique available for direct determination of tissue oxygen content. Instead, clinicians need to rely on various methods that attempt to measure perfusion such as Doppler ultrasound, or an indirect measure of tissue oxygenation, transcutaneous oxygen measurement (TcO2). The latter detects oxygen diffusing through skin warmed to 42-44? C by the instrument, which has a complex relationship to the actual pO2 in the tissue. This project will apply 2 emerging techniques; electron paramagnetic resonance (EPR) oximetry and near infrared spectroscopy (NIR) to measure tissue oxygenation more directly and reliably in healthy volunteers. The ultimate aim is to extend the techniques to diabetic patients for clinical management of the disease. EPR is a new oximetry modality that directly measures tissue oxygen content and NIR oximetry characterizes the amount and saturation of intravascular hemoglobin, so a combination of these 2 techniques will provide complementary information about oxygen delivery and local concentration, providing a more complete picture of the tissue oxygenation. The major potential advantages of EPR and NIR are that they provide information not previously available, namely direct tissue oxygen content, and that meaningful repeated measurements can be obtained non-invasively over a long period of time. This information would be extremely useful for characterizing the status of the disease, and to determine the effects of therapeutic intervention on tissue oxygenation, and the relationship between oxygenation and progression of the disease. Promising preliminary results have been obtained, indicating the feasibility of following tissue oxygen in humans for years. If the promise of these techniques is fulfilled, clinicians will have a new powerful tool for management of peripheral vascular disease, based on fundamental pathophysiology. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK072112-02
Application #
7230214
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Jones, Teresa L Z
Project Start
2006-07-01
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$194,079
Indirect Cost
Name
Dartmouth College
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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Williams, Benjamin B; Khan, Nadeem; Zaki, Bassem et al. (2010) Clinical electron paramagnetic resonance (EPR) oximetry using India ink. Adv Exp Med Biol 662:149-56
Khan, Nadeem; Mupparaju, Sriram P; Mintzopoulos, Dionyssios et al. (2008) Burn trauma in skeletal muscle results in oxidative stress as assessed by in vivo electron paramagnetic resonance. Mol Med Report 1:813-819
Khan, Nadeem; Williams, Benjamin B; Hou, Huagang et al. (2007) Repetitive tissue pO2 measurements by electron paramagnetic resonance oximetry: current status and future potential for experimental and clinical studies. Antioxid Redox Signal 9:1169-82