Assessment of Reconstructive Surgical Flaps Using Spatially Resolved Tissue Oxima

描述（由申请人提供）：使用组织转移皮瓣是一种将组织从供体位置移动到受体位置并将动脉和静脉重新连接到受体位置的血管的方法。这些程序使创伤后的重建手术，以及手术切除癌症后。皮瓣转移手术失败的原因有多种：动脉或静脉机械性阻塞导致血管功能不全，皮瓣转移过程中血流量不足对移植组织造成损伤，或缺血再灌注损伤。游离组织移植术后第一天的特点是存在微血管并发症和移植组织坏死损失的风险。失去游离皮瓣对外科医生和病人来说都是毁灭性的经历。移植组织的组织氧合和微血管血流的维持对皮瓣的存活至关重要。几项研究表明，频繁监测和早期发现损害可导致早期干预，从而减少导致组织损失的破坏性并发症的数量。在显微外科时代早期，皮瓣监测仅用于临床观察皮肤颜色、毛细血管充盈和真皮出血。然而，与人员配备和临床评估皮瓣灌注的主观差异有关的问题导致了对皮瓣监测的客观方法的探索。漫射光谱学是测量体内局部组织氧合的一种很有前途的技术。DOS是一种定量近红外（NIR）光谱技术，可以确定氧和脱氧血红蛋白、脂肪和水等发色团的绝对浓度。调制成像（MI）是BLI发明的一种基于DOS原理的近红外成像方法，采用图案照明来询问生物组织。这种非接触式方法可以在宽视场范围内快速定量测定发色团的光学性质和体内浓度。本研究的中心目标是进一步发展调制成像技术，并评估其作为确定组织重建皮瓣状态的一种手段的可行性。在第一阶段，我们使用背蒂皮瓣啮齿动物模型进行了体内心肌梗死研究。背蒂皮瓣易于实现创面的缺血再灌注控制。这使我们能够利用心肌梗死推断出几天内组织血红蛋白、氧合和水合作用的空间分辨图。在第二阶段，我们建议开发和验证一种临床使用的心肌梗死仪器。研究将首先在成年约克郡猪局部血管充血的控制模型中评估心肌梗死的性能。随后将进行一项研究，在临床情况下使用MI和潜在的竞争FDA批准的设备，以评估局部皮瓣状态。与本文概述的II期研究并行，我们将积极追求基于MI的医疗设备的商业化。

DESCRIPTION (provided by applicant): The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries & veins to the blood vessels at the recipient site. These procedures enable reconstructive surgery after trauma, as well as after surgical resection of cancer. Flap transfer surgery is subject to failure via a number of modes including vascular insufficiency caused by mechanical obstruction of the artery or vein, injury caused to the transferred tissues due to the lack of blood flow during the flap transfer, or due to ischemia-reperfusion injury. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a free flap is a devastating experience to both the surgeon and the patient. Tissue oxygenation and maintenance of microvascular blood flow in grafted tissues are crucial for flap viability. Several studies have demonstrated that frequent monitoring and early detection of compromise results in earlier intervention which reduces the number of devastating complications that lead to tissue loss. Early in the era of microsurgery, flap monitoring was performed with only clinical observation of skin color, capillary refill, and dermal bleeding. However, issues related to staffing and subjective variations in clinical assessment of a flap's perfusion have led to the search for objective methods of flap monitoring. One promising technology for measuring local tissue oxygenation 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. The central aim of the proposed research is to further the development of Modulated Imaging and to assess the viability of this as a means to determine status of tissue reconstruction flaps. In Phase I, we carried out an in-vivo MI study using a dorsal pedicle flap rodent model. The dorsal pedicle flap is easily implemented to establish controlled ischemia and re-perfusion of the wounds. This allowed us to employ MI to deduce spatially resolved maps of tissue hemoglobin, oxygenation and hydration over the course of several days. In Phase II we propose to develop and validate an MI instrument for clinical use. Investigations will first evaluate the performance of MI in a controlled model of partial vascular congestion using adult Yorkshire pigs. This will be followed by a study in which MI and a potentially competing FDA cleared device will be employed in a clinical situation in order to assess local flap status. In parallel with the Phase II research outlined herein, we will aggressively pursue commercialization of a medical device based on MI.