Assessment of Reconstructive Surgical Flaps Using Spatially Resolved Tissue Oxima

描述（由申请人提供）：组织转移皮瓣的使用是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部位的血管的方法。这些手术使得创伤后以及癌症手术切除后的重建手术成为可能。皮瓣转移手术通过许多模式而失败，包括由动脉或静脉的机械阻塞引起的血管功能不全，由于在皮瓣转移期间缺乏血流或由于缺血-再灌注损伤而对转移的组织造成的损伤。游离组织移植后的第一个术后天数的特征在于微血管并发症和坏死导致的移植组织损失的风险。游离皮瓣的丢失对外科医生和患者来说都是一种毁灭性的经历。 组织氧合和维持移植组织中的微血管血流对于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导致早期干预，减少了导致组织损失的破坏性并发症的数量。在显微外科时代的早期，皮瓣监测仅进行皮肤颜色，毛细血管再充盈和皮肤出血的临床观察。然而，有关人员配备和主观的皮瓣灌注的临床评估的变化的问题，导致了皮瓣监测的客观方法的搜索。 一种用于测量体内局部组织氧合的有前途的技术是漫射光谱（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。 拟议研究的中心目标是进一步发展调制成像，并评估其作为确定组织重建皮瓣状态的手段的可行性。在第一阶段，我们进行了一项体内心肌梗死研究，使用背蒂皮瓣啮齿动物模型。背侧带蒂皮瓣很容易实现伤口的控制性缺血和再灌注。这使我们能够采用MI来推断几天内组织血红蛋白、氧合和水合的空间分辨图。在第二阶段，我们建议开发和验证MI仪器用于临床。研究将首先使用成年约克郡猪在部分血管充血的受控模型中评估MI的表现。随后将进行一项研究，在该研究中，将在临床情况下使用MI和潜在竞争的FDA批准器械，以评估局部皮瓣状态。在本文概述的II期研究的同时，我们将积极寻求基于MI的医疗器械的商业化。

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.