BOLD MRI: Application to Intra-renal Oxygenation

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DESCRIPTION (provided by applicant): Radiocontrast nephropathy (RCN) is a third common cause of hospital acquired renal failure, accounting for 11% of incidence. With the continuing rise in the number of diagnostic imaging procedures and because it is a hospital acquired syndrome, the need for prevention is most compelling. However, the mechanisms behind the development of RCN remain not fully understood. Many interventions proposed based on animal testing have failed in human trials. The possible reasons for this disconnect may be due to: (1) animal models not adequately representing the human physiology, (2) outcome measures used in animal models differ from those used in the clinic, (3) invalid hypothesis etc.. Over the last two decades significant progress has been made in terms of understanding the oxygenation status within the kidney and it is now well appreciated that regions within the kidney survive under hypoxic conditions. In order for the kidney to survive in the hypoxic milieu, powerful control mechanisms have evolved that maintain oxygen sufficiency even under the threat of external stimuli such as during administration of contrast media. It is believed that compromise in the ability of the kidney to activate these control mechanisms during a "stress" may be the cause for the development of renal failure following stimuli such as contrast media. Based on these hypotheses, novel animal models have been proposed and validated. These are simpler compared to previous models that necessitate surgical manipulations, and more importantly better represent the functional aspect of the human condition. Additionally, the techniques available for monitoring intra-renal oxygenation have continuously improved. Blood oxygenation level dependent (BOLD) MRI technique has been shown to be sensitive and efficacious in evaluating renal oxygenation both in rat and human kidneys. In addition, better understanding of the oxygenation status has given rise to new targets for intervention. Based on this background, this proposal extends our present findings in healthy and hypertensive kidneys with BOLD MRI to better understand the acute hemodynamic responses following contrast administration in functional models of RCN and in RCN prone diabetic rats. We will additionally acquire markers that are used in the clinic. We will also test the efficacy of novel interventions targeted at relieving hypoxia. We will further use sodium MRI to monitor acute changes following contrast media and correlate them with BOLD MRI measurements. Successful outcome should have a significant impact on the development of preventive strategies for RCN. PUBLIC HEALTH RELEVANCE Radiocontrast induced renal failure is a common hospital acquired syndrome and because the consequences could be severe including death, preventive strategies are highly sought after. With the continuous increase in the number diagnostic procedures, the relevance and significance of this problem is growing. Our proposed study will allow for better understanding of the mechanisms behind the development of this syndrome and develop novel preventive strategies.