Perioperative Diffuse Optical Imaging of Tissue Blood Flow and Oxygenation for Optimization of Mastectomy Skin Flap Viability

摘要 大约一半的乳腺癌患者接受了乳房切除术。乳房切除术后乳房 重建对身体形象、性行为、自尊和生活质量都有好处。临床预后不佳 乳房重建术后常伴有乳房切除后皮瓣坏死或其他并发症 与伤口组织体积的血流和氧合不足有关。MSFN与伤口裂开 导致了一些挑战，包括伤口管理问题，辅助治疗的延误，美容 妥协、植入物挤压、病人痛苦和经济损失。一种允许外科医生 在避免并发症的同时，围手术期评估和优化皮瓣的保存是确保 成功的临床结果。尽管已经探索了替代技术来识别缺血-缺氧 有坏死风险的组织，没有一种得到普遍接受，因为每种技术都有一些挑战 降低其临床实用性的问题。此外，没有一种单一的技术可以同时提供血流和 氧合信息，这是准确评估皮瓣存活所必需的。我们最近的创新 近红外散斑对比漫相关层析成像技术的发展提供了一种 用于连续2D/3D血流分布成像的非侵入性(无染料)和非接触式手段 通过大/厚组织体积，如乳房切除皮瓣。我们建议将这一SCDCT扩展 新一代多波长scDCT(MW-scDCT)装置的样机 乳房切除皮瓣血流量和氧合分布。一种新的高速二维映射算法 并将开发3D图像重建，以适应快速在线评估皮瓣 血流动力学。该MW-scDCT系统将使用标准的组织模拟模体进行测试/优化 (AIM 1)，并对照商用染料荧光血管造影仪(SPY Elite®)进行校准/验证 在猪(目标2)和患者(目标3)中进行乳房扩张器-植入物乳房切除术 重建。体内研究将确定我们的MW-SCDCT对术中预后的预测能力 MSFN区域/体积和术后增量扩张器体积的优化以降低 MSFN和其他并发症。我们预计，联合测量术前基线和 术中皮瓣血流和氧合的改变将提供更准确的皮瓣评估 生存能力优于一次性单参数测量(即血流量、血氧或荧光 灌流)。研究结果将为设计MW-SCDCT指导的临床试验提供理论基础 乳房切除乳房重建术可减少术后并发症和医疗费用。此外， 这种非侵入性(无染料)、非接触、连续且经济高效的成像系统有可能 围手术期在许多其他临床环境中使用，特别是在接触测量可能不可能的情况下， 例如用于连续和纵向监测烧伤、伤口和其他类型的组织瓣。

ABSTRACT Mastectomy is performed on approximately half of women with breast cancer. Postmastectomy breast reconstruction has benefits for body image, sexuality, self-esteem, and quality of life. Poor clinical prognoses after breast reconstruction often involve mastectomy skin flap necrosis (MSFN) or other complications associated with the lack of blood flow and oxygenation to wound tissue volumes. MSFN and wound dehiscence leads to a number of challenges, including wound management problems, delays to adjuvant therapy, esthetic compromise, implant extrusion, patient distress, and financial loss. A technology that allows surgeons to perioperatively assess and optimize preservation of skin flaps while avoiding complications is essential to ensure successful clinical outcomes. Although alternative techniques have been explored to identify ischemic-hypoxic tissues at risk of necrosis, none have achieved universal acceptance as each technique has a few challenging issues that decrease its clinical usefulness. Moreover, no single technique provides both blood flow and oxygenation information, which are essential for precise assessment of skin flap viability. Our recent innovative development of near-infrared speckle contrast diffuse correlation tomography (scDCT) technique provides a noninvasive (dye-free) and noncontact means for continuous 2D/3D imaging of blood flow distributions throughout large/thick tissue volumes such as mastectomy skin flaps. We propose to extend this scDCT prototype to a next generation multi-wavelength scDCT (MW-scDCT) device for perioperative imaging of both blood flow and oxygenation distributions in mastectomy skin flaps. New high-speed algorithms for 2D mapping and 3D image reconstruction will be developed to accommodate rapid online assessment of skin flap hemodynamics. This MW-scDCT system will be tested/optimized using standard tissue-simulating phantoms (Aim 1) and calibrated/validated against a commercial dye-based fluorescence angiography device (SPY Elite®) in swine (Aim 2) and patients (Aim 3) undergoing mastectomy with expander-implant based breast reconstruction. The in vivo studies will determine the capability of our MW-scDCT for intraoperative prediction of MSFN regions/volumes and postoperative optimization of incremental expander volumes to reduce risks of MSFN and other complications. We expect that combined measurements of preoperative baseline and intraoperative alteration in skin flap flow and oxygenation will provide a more accurate assessment of skin flap viability than a one-time single-parameter measurement (i.e., blood flow, blood oxygenation, or fluorescence perfusion). Study outcomes will provide the rationale for designing MW-scDCT guided clinical trials of mastectomy with breast reconstruction to reduce postoperative complications and healthcare costs. Moreover, this noninvasive (dye-free), noncontact, continuous, and cost-efficient imaging system has the potential for perioperative use in many other clinical settings, especially where contact measurements may not be possible, such as for continual and longitudinal monitoring of burns, wounds, and other types of tissue flaps.