Modulated Imaging in Comprehensive Assessment of Diabetic Foot Ulcer Development

描述（由申请人提供）：2010年，糖尿病影响全球2.85亿成年人，预计到2030年，患病率将增加至4.39亿人。足部溃疡仍然是糖尿病的主要合并症，并且在1型和2型受试者的一生中折磨多达15%至25%。事实上，大约85%的糖尿病患者下肢截肢之前都有足部溃疡。未经治疗的糖尿病足溃疡和随后的截肢对糖尿病患者的生活质量有深远的影响。最后，在2007年，美国糖尿病及其并发症的治疗产生了至少1160亿美元的直接成本，其中至少33%的成本与足部溃疡的治疗有关。组织灌注、血氧测定和水合作用已被证明可预测溃疡愈合和形成。这些数量提供了对皮肤的新陈代谢，微观结构和健康的洞察。一种用于测量局部组织灌注、氧合、水合和体内微观结构的有前景的技术是漫射光谱（DOS）。DOS是一种定量近红外（NIR）光谱技术，可以确定发色团的绝对浓度，如氧合和脱氧血红蛋白，脂肪和水。调制成像（MI）是BLI发明的一种近红外成像方法，基于DOS原理，采用图案化照明来询问生物组织。这种非接触式方法能够在宽视场内快速定量测定发色团的光学性质和体内浓度。更重要的是，MI还可用于测量组织的降低的散射系数，从而深入了解溃疡形成和愈合期间由于胶原瘢痕形成、愈伤组织形成、坏死或炎症引起的组织中的微观结构变化。拟议研究的中心目的是证明调制成像（MI）作为预测/监测糖尿病足并发症的一种手段。我们建议开发两层计算技术，这将提高从具有强黑色素沉着或厚胼胝的足部皮肤获得的数据的准确性和精确性。一旦该MI系统、算法和软件在组织模拟体模上得到验证，我们将从显示糖尿病足溃疡的受试者中收集数据。将使用这些数据开发溃疡形成和愈合的预测模型。该初步研究的结果将用于仔细设计II期研究，以建立基于MI的模型预测溃疡形成和愈合的预测能力。 公共卫生相关性：足部溃疡仍然是糖尿病的主要并发症，在1型和2型糖尿病患者的一生中，有多达15 - 25%的患者患有足部溃疡。我们建议使用新的成像技术（调制成像），以促进溃疡形成或不愈合的预测。我们的技术有可能显着降低糖尿病足溃疡的人力和财力成本。

DESCRIPTION (provided by applicant): 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.