Foot ulcers are an important complication of diabetes mellitus and often precede lower- extremity amputation. Insufficient perfusion, due to peripheral vascular disease and/or diabetes, of the tissues may be the most important component contributing to ulcer formation and limiting healing. However, it is historically very difficult to assess distal leg and foot perfusion accurately. We recently demonstrated a novel, non-contrast, magnetic resonance imaging (MRI)-based approach to quantify skeletal muscle microcirculation, specifically skeletal muscle blood flow and oxygen extraction fraction distributions. The objective of this study is to translate these techniques to characterize the skeletal muscle microcirculation in calf and foot muscles in groups of patients with diabetes, with and without ulcers. The long term goal is to promote microcirculation as a prime evaluation target before embarking on interventional treatment for limb preservation in patients with diabetes.
Two specific aims will be addressed.
Specific Aim 1 will determine the relationships between regional blood flow, oxygen extraction fraction, and the presence of pedal ulcers in patients with diabetes, with and without peripheral vascular disease.
Specific Aim 2 will determine how pre-surgical and post-surgical measures of skeletal muscle blood flow and oxygen extraction fraction are related to wound healing following vascular surgery in patients with DM who also have peripheral vascular disease. All study will be performed at rest and during a controlled exercise. It is hypothesized that increases in skeletal muscle blood flow and oxygen extraction fraction in plantar muscles during exercise is substantially attenuated in patients with diabetes, peripheral vascular disease, and a plantar foot ulcer. And this attenuation is inversely correlated with foot ulcer healing in patients' post-revascularization. The completion of this study will provide a foundation for further detailed understanding of role of the local wound perfusion, which is essential to developing a management plan and establishing prognosis for patients with a foot ulcer.

Public Health Relevance

This project is to evaluate the role of regional skeletal muscle perfusion / oxygenation in the presence of foot ulcer in patients with diabetes. A newly developed non-contrast magnetic resonance imaging technique will be employed to assess regional skeletal muscle perfusion and oxygen extraction fraction in calf and foot, at rest and during a challenge exercise. It is hypothesized that these regional perfusion and oxygenation indices will be progressively attenuated with the severity of diabetes, peripheral vascular disease, and presence of a foot ulcer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK105322-03
Application #
9399657
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Jones, Teresa L Z
Project Start
2016-03-01
Project End
2019-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130