Assessment of Reconstructive Surgical Flaps Using Spatially Resolved Tissue Oxima

描述(申请人提供)：组织转移瓣的使用是一种将组织从供体部位移至受者部位，并将动脉和静脉重新连接到受者部位的血管的方法。这些程序使创伤后的重建手术以及癌症手术切除后的重建手术成为可能。由于动脉或静脉的机械性阻塞导致的血管功能不全，由于在转移过程中缺乏血液流动而导致移植组织损伤，或由于缺血再灌注损伤，皮瓣转移手术往往会失败。游离组织移植术后第一天的特点是微血管并发症和移植组织因坏死而丢失的风险。对于外科医生和患者来说，失去游离皮瓣都是一种毁灭性的经历。组织氧合和移植组织中微血管血流量的维持对皮瓣存活至关重要。一些研究表明，频繁监测和及早发现损害会导致更早的干预，从而减少导致组织丢失的破坏性并发症的数量。在显微外科时代的早期，皮瓣监测仅通过临床观察皮肤颜色、毛细血管充盈和皮肤出血来进行。然而，与人员配备有关的问题和临床评估皮瓣灌注量的主观差异导致了对皮瓣监测的客观方法的探索。漫反射光谱分析(DOS)是一种很有前途的体内局部组织氧合测量技术。DOS是一种定量近红外(NIR)光谱技术，可以测定生色团的绝对浓度，如氧合和脱氧血红蛋白、脂肪和水。调制成像(MI)是BLI发明的一种基于DOS原理的近红外成像方法，它使用图案化照明来询问生物组织。这种非接触式的方法可以在大视场范围内快速定量测定发色团的光学性质和体内浓度。这项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，我们使用背侧带蒂皮瓣啮齿动物模型进行了体内心肌梗死研究。背侧带蒂皮瓣容易实现创面的可控缺血和再灌流。这使得我们可以使用MI来推断几天过程中组织血红蛋白、氧合和水合的空间分辨地图。在第二阶段，我们建议开发和验证临床使用的MI仪器。研究将首先评估MI在使用成年约克夏猪的部分血管充血受控模型中的表现。接下来将进行一项研究，在这项研究中，MI和潜在竞争对手FDA批准的装置将用于临床情况，以评估局部皮瓣状态。在本文概述的第二阶段研究的同时，我们将积极推进基于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.