SBIR-STTR Award

Diabetes mellitus affected 285 million adults worldwide in 2010 and is expected to increase in prevalence to 439 million people by the year 2030. Foot ulceration continues to be a major comorbidity of diabetes and afflicts as many as 15 to 25% of subjects with type 1 and 2 during their lifetime. In fact, roughly 85% of all lower extremity amputations in patients with diabetes mellitus are preceded by a foot ulcer. Untreated diabetic foot ulceration and subsequent amputation has a profound impact on the quality of life of the diabetic patient. Finally, in 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs;at least 33% of these costs were linked to the treatment of foot ulcers. Tissue perfusion, oximetry, and hydration have been shown to predict ulcer healing and formation. These quantities provide insight into the metabolism, microstructure and health of the skin. One promising technology for measuring local tissue perfusion, oxygenation, hydration, and microstructure in-vivo is diffuse optical spectroscopy (DOS). DOS is a quantitative near-infrared (NIR) spectroscopy technique that can determine absolute concentrations of chromophores such as oxy &deoxy hemoglobin, fat and water. Modulated Imaging (MI) is a NIR imaging method invented at BLI that is based on the principles of DOS and employs patterned illumination to interrogate biological tissues. This non-contact approach enables rapid quantitative determination of the optical properties and in-vivo concentrations of chromophores over a wide field-of-view. More importantly, MI can also be used to measure the tissue's reduced scattering coefficient and thus gain insight into microstructural changes in the tissue during ulcer formation and healing due to collage scarring, callus formation, necrosis, or inflammation. The central aim of the proposed research is to prove Modulated Imaging (MI) as a means to predict/monitor complications of the diabetic foot. We propose to develop two-layer computational techniques that will enhance the accuracy and precision of data obtained from foot skin having strong melanin pigmentation or thick callus. Once this MI system, algorithm, and software have been validated on tissue simulating phantoms, we will collect data from subjects exhibiting diabetic foot ulceration. A predictive model for ulcer formation and healing will be developed using this data. Results from this pilot study will be used to carefully design a Phase II study to establish the predictive power of MI-based models to predict ulcer formation and healing.

Public Health Relevance:
Foot ulceration continues to be a major co-morbidity of diabetes and afflicts as many as 15 to 25% of subjects with type 1 and type 2 during their lifetime. We propose to use novel imaging technology (Modulated Imaging) to facilitate prediction of ulcer formation or non-healing. Our technology has the potential to significantly reduce the human and financial cost of diabetic foot ulceration.

Diabetes mellitus affected 382 million adults worldwide in 2013 and is expected to increase in prevalence to 592 million people by the year 2035. Foot ulceration continues to be a major comorbidity of diabetes and afflicts as many as 25% of subjects with type 1 and 2 diabetes during their lifetime. Lower limb amputations due to poor DFU management are a global burden that is associated with a 77% 5-year mortality rate and cumulatively costs the system approximately $70,000 per patient. Effective prevention and treatment of foot ulcers can be hindered due to a lack of objective standards to quantitatively track foot health and assess treatment outcomes. The broad goal of this research is to develop Modulated Imaging, a new clinically-viable tool which provides quantitative insight into disease stage, progression and therapeutic response, into a clinically-viable tool for screening and managing diabetic foot ulcers. MI is a non-contact imaging technology that determines the in-vivo concentrations of subsurface chromophores relevant to tissue health (i.e. hemoglobin, oxygenation, edema and scattering). The goal of this proposal is to develop a user-friendly dedicated MI platform system for studying the value of MI-derived biometrics (like hemoglobin, oxygenation, and scattering) in the diabetic foot. In this Phase II program, we will build a DFU-MI device and perform three pilot studies to assess the capability of our technology to impact diabetic foot care. First, we will characterize vascular reactivity in control and feet considered “at risk” for ulcer to determine normative MI biometrics. Second, we will study our ability to predict new wound formation in feet that are considered in “remission” but with a >35% chance of re-ulceration. Finally, we will study lower limb perfusion changes after vascular intervention for and existing wound to assess efficacy prior to wound closure. Our Phase II research will determine the insertion point of MI technology into DFU clinical care and provide insight to future Phase III clinical study hypotheses and designs in order to build a medical imaging device with indications specific to wound prediction and healing.

Public Health Relevance Statement:
NARRATIVE Effective prevention and treatment of foot ulcers can be hindered due to a lack of objective standards to monitor progression. The goal of this research is to develop Modulated Imaging, a new optical technology which provides quantitative insight into disease status and therapeutic response, into a clinically-viable tool for screening and managing diabetic foot ulcers.

NIH Spending Category:
Bioengineering; Clinical Research; Diabetes; Prevention

Project Terms:
absorption; Academia; Acute; Adult; Affect; Algorithms; Arizona; base; Biological; Biometry; Blood Vessels; Bone callus; Caring; chromophore; Clinical; clinical application; clinical care; Clinical Data; Clinical Research; commercialization; Comorbidity; Computer Simulation; Computer software; cost; County; Coupled; Data; design; Development; Devices; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Disease; Disease remission; Dorsal; Edema; expectation; foot; Foot Ulcer; Frequencies; Funding; Future; Goals; Healed; healing; Health; Hemoglobin; Image; Imaging Device; Imaging technology; Impaired wound healing; improved; in vivo; indexing; Industry; insight; instrumentation; Intervention; Isolated limb perfusion; Light; Lighting; limb amputation; Limb Salvage; Lower Extremity; Marketing; Measures; Medical; Medical Imaging; Mining; Modeling; Monitor; Morphologic artifacts; mortality; Motion; new technology; Optics; Oranges; Outcome; Patient risk; Patients; Pattern; Phase; Pilot Projects; prediction algorithm; Prevalence; prevent; Prevention; programs; Property; Recording of previous events; Research; Research Design; Risk; screening; Side; Skin; Small Business Innovation Research Grant; spectrograph; Staging; System; systems research; Technology; Testing; Time; tissue oxygenation; Tissues; tool; Translations; Treatment outcome; treatment response; Ulcer; user-friendly; Water; Work