DETECTION OF HYPOXIA IN SICKLE CELL ANEMIA BY BOLD MRI

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(Adapted from Applicant's Abstract) Treatment of sickle cell painful crisis has suffered from a lack of objective criteria for detecting progression of crisis and use in evaluating treatment protocols. To date, MRI of painful crisis has yielded results which are intriguing but difficult to evaluate. Detection of hypoxia in regions with acute pain may yield a useable marker. The technology for in vivo observation of blood perfusion and tissue oxygenation by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has matured into a sensitive technique an can be applied to these problems. The investigators will test the hypothesis that painful crisis of the limbs is accompanied by areas of blood hypoxia due to partial obstruction of the circulation which can be detected by BOLD MRI. The investigators also test the hypothesis that the stereotypical repetition of painful crisis as the same sight might be the consequence of congenital or acquired alteration (by previous crises or other effects) in the microcirculation that predispose to repeat crises in the same site. The investigators will also examine the hypothesis that HU will reduce the extent of the area affected and/or the degree of blood hypoxia in areas prone to crisis. The investigators have demonstrated in transgenic mice expressing the BetaS-globin gene that BOLD-MRI can detect the presence of high levels of deoxy hemoglobin (blood hypoxia) in tissues such as the medulla of the kidney which have been shown to have very low oxygen tension by other means. Highly deoxygenated sickle cell blood is at risk of polymer formation and the microcirculation is a risk of vaso- occlusion. The investigators propose here to use BOLD-MRI to detect blood deoxygenation in adult patients with sickle cell painful crisis. A goal of these studies to separate acute, ongoing events during sickle cell painful crisis from the results of previous episodes of ischemia. Previous approaches to detection of pathological changes occurring during the course of sickle cell painful crisis such as 99mTc bone scans and MRI are too sensitive to the presence of old infarcts to allow detection of new infarcts without prior baseline studies. If successful, this approach may allow the unique visualization of poorly perfused regions without reference to baseline studies.