Prognostic Imaging and Blood Markers of Wound Healing Among Patients with Diabetic Foot Ulcers
The objective of this proposal is to establish and translate novel noninvasive imaging methods and blood markers prognostic of incomplete wound healing in the setting of diabetic foot ulcers (DFU). Over 30 million people live with diabetes in the United States. Diabetic foot ulcers (DFU) account for 25-50% of all diabetes-related hospital costs in the US totaling approximately $40 billion per year and are often the first recognized sign of impending limb loss. The lifetime risk for DFU is up to 25% and its treatment is resource-intensive requiring antibiotics, frequent wound care, and surgical procedures, yet 1-year healing rates are only 75%. Once an ulcer forms, the risk of limb loss is high with up to 20% of patients undergoing lower-extremity amputation. Strong basic and clinical evidence demonstrates both initiation of ulcers and poor wound healing arise from reduced tissue perfusion and ischemia. Diminished oxidative capacity in circulating immune cells have been implicated in disease states associated with poor wound healing. Currently there are no effective clinical tools for predicting DFU. With the long-term goal of improving the clinical outcomes, we will examine the influence of microvascular impairment and reduced immune cell energetics on wound healing in patients with DFU. In human subjects, we have demonstrated both robust in vivo magnetic resonance imaging approaches for quantifying resting tissue perfusion and microvascular reserve. We have also demonstrated the ability to measure reductions in monocyte reserve respiratory capacity in obesity compared with normal weight human subjects. With this technical foundation established, the proposed study will extend these methods for improved characterization of incomplete wound repair in diabetic foot ulcers. In this pilot study, we will pursue two related specific aims. In Aim 1, we will establish MRI measurements to characterize microcirculatory abnormalities in patients with diabetic foot ulcers. In Aim 2, we will test for reduced monocyte reserve respiratory capacity in patients with diabetic foot ulcers. If successful, this work will establish proof-of-principle data for the use of imaging and blood markers to assess diminished microcirculatory and immune cellular energetic capacity in the setting of DFU. The results from this pilot study are expected to provide important data on measurement sensitivity to support the design of follow-up longitudinal work to examine and disentangle the combined and/or independent influences of microcirculatory and energetic impairment in DFU patients that exhibit incomplete wound repair; this will form the basis of an R-level NIH proposal. Ultimately, we expect this will provide novel information for more effective treatment strategies of DFU and allow for improved patient selection for trials evaluating novel DFU wound healing therapies.

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