Hemodynamic Noninvasive Skin Cancer Diagnostics

 皮肤癌是美国最常见的癌症形式，每年占所有诊断癌症的一半以下（350万例诊断）和12，980例死亡，每年治疗费用为25亿美元。皮肤癌的早期和准确诊断对患者的预后和医疗保健成本有显著影响，但仍然是一种高度主观的技能，现有的诊断设备要么提供有限的积极预测价值，要么需要高度专业化的培训。误诊会导致皮肤癌被遗漏，以及大量不必要的皮肤科医生转诊和不必要的活检。 我们一直在开发一种新的方法和设备，用于基于皮肤肿瘤中压力诱导血流的时间动态测量的皮肤癌的快速和非侵入性检测。拟议研究的中心假设是，与良性痣相比，皮肤肿瘤中响应于外部机械压力的血流动力学是不同的，从而提供了诊断机会。多项研究表明，皮肤癌的血管化程度明显高于正常皮肤或良性痣，而肿瘤血管网的形态高度不规则，导致血管对血流的阻力变化和间质液压力高度升高。所提出的方法依赖于使用光学探针测量皮肤肿瘤组织中的空间和时间分辨的光吸收，所述光学探针也充当压力施加装置。该方法能够表征在压力下移位的血液量以及血液移位和再填充的动力学。我们的初步临床研究数据显示，无论是体积和压力诱导的血流速度显着高于皮肤癌比良性痣。在此，我们建议（1）设计和构建更先进的设备，以更详细地研究基底细胞癌和鳞状细胞癌以及黑色素瘤肿瘤中的压力诱导动力学;（2）研究影响肿瘤组织中压力诱导血流动力学的仪器和生理学依赖性因素，并改进我们的数据分析算法，以优化我们设备的灵敏度和特异性;以及（3）开发和测试下一代优化的皮肤癌检测器。 该项目的长期目标是开发一种简单易用、低成本的非侵入性皮肤癌诊断方法和设备，该方法和设备将（1）促进全科临床医生和执业护士对可疑皮肤区域进行敏感、特异和非主观的评估，（2）能够精确定位患者进行活检和/或升级护理，（3）全面减少皮肤癌 治疗费用。

 DESCRIPTION (provided by applicant): Skin cancer is the most common form of cancer in the US, each year accounting for just under half of all diagnosed cancers (3.5 million diagnoses) and 12,980 deaths with annual treatment costs of at $2.5 billion. Early and accurate diagnosis of skin cancer has significant impact on patient outcomes and health care costs but remains a highly subjective skill, with existing diagnostic devices either offering limited positive predictie value or requiring highly specialized training. Mis-diagnoses results in missed skin cancers as well as large numbers of unneeded referrals to dermatologists and unnecessary biopsies. We have been developing a novel method and device for a fast and non-invasive detection of skin cancer based on measurements of the temporal dynamics of pressure-induced blood flow in the cutaneous tumors. The central hypothesis of proposed research is that the dynamics of blood flow in response to external mechanical pressure is different in cutaneous tumors as compared to benign nevi thus presenting a diagnostic opportunity. Multiple studies have shown that skin cancer is significantly more vascularized than normal skin or benign nevi while the morphology of tumor vascular network is highly irregular contributing to changes in vascular resistance to blood flow and highly elevated interstitial fluid pressure. The proposed method relies on measuring the spatially and temporally resolved light absorption in the cutaneous tumor tissue using an optical probe which also acts as pressure application device. The method enables to characterize both the amount of blood displaced under pressure and the dynamics of blood displacement and refill. Our preliminary data from a pilot clinical study show that both the volume and the rate of the pressure-induced blood flow are significantly higher in cutaneous cancer than in benign nevi. Here we propose (1) to design and build more advanced devices to perform more detailed investigation of pressure-induced dynamics in basal and squamous cell carcinoma, and melanoma tumors; (2) to investigate instrument- and physiology-dependent factors that affect pressure-induced hemodynamics in tumor tissue and to improve our data analysis algorithms in order to optimize sensitivity and specificity of our device; and (3) to develop and test next generation optimized skin cancer detector. The long-term goal of the project is to develop a simple-to-use and low-cost non-invasive skin cancer diagnostic method and device that will (1) facilitate sensitive, specific and non-subjective assessment of suspect skin regions by general practice clinicians and nurse practitioners, (2) enable precise targeting of patients for biopsies and/or escalation of care and (3) provide overall reduction in skin cancer treatment costs.