The comprehensive evaluation of the feasibility, reliability and diagnostic capability of phosphorus NMR spectroscopy in the study of independently diagnosed peripheral vascular disease over an adequate population to identify categories of severity, etiology, therapy, and prognosis, is a general goal of an intensive study using phosphorus NMR spectroscopy and a standardized protocol for evaluation of oxygen delivery to claudicated limbs. An 11 1/2"""""""" clear bore NMR spectrometer, complemented by access to a 30"""""""" clear bore spectrometer affords an opportunity to evaluate muscle biochemistry in the limbs of over 85% of the population of peripheral vascular diseased patients and normal controls. The standard protocol of """"""""top-up"""""""" exercises outside the magnet and insertion of the leg in the magnet, used in critical evaluation of over 209 limbs provides significant correlations with diagnosis by ankle pressure index. We plan to extend the study population by 400 patients so that populations can be divided based on severity, etiology and therapeutic procedures, and, in particular post-operative recovery. Two variations of the basic """"""""toe-up"""""""" exercise protocol are specialized for particular patient populations; 1) resting phosphocreatine/phosphate determinations in severly diseased patients and 2) in-magnet graded exercise protocols will be developed for patients with subclinical symptoms, and for those whose degree of claudication is moderate. A new method of data analysis, based upon the Michaelis-Menten hypothesis and standard enzyme-substrate kinetics affords insight into the results of these 3 portocols; recovery kinetics, graded exercise and resting state values, which allows an estimation of the maximal oxygen delivery capability to the tissue. The goals of this study are to establish the feasibility and reliability of performing clinical NMR studies, and to quantify categories of severity, etiology, and the effectiveness of therapeutic measures. The ultimate goal is to collect a reliable data bank for NMR evaluation of peripheral vascular disease, which can be used as a basis for further evaluation of the use of NMR in noninvasive """"""""in vivo"""""""" detection of disease and monitoring of therapeutic intervention.

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National Heart, Lung, and Blood Institute (NHLBI)
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Diagnostic Radiology Study Section (RNM)
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University City Science Center
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