Infrared Skin Imaging to Transform Noninvasive Diagnosis and Management of Skin Disease

项目概要/摘要 皮肤病影响四分之一的美国人，每年花费750亿美元。诊断依赖于目视检查， 但视觉评估的主观性可能导致皮肤癌误诊或痛苦的死亡 误诊为可治疗的慢性炎症非白人美国人占40%， 人口，并面临进一步的挑战，因为疾病可能会出现更微妙的色素沉着的皮肤， 系统性诊断不足和治疗不足。皮肤活检更客观，但不是所有患者，特别是 儿童，容忍侵入性程序，并有关于过度使用和诊断率低的关注， 活组织检查因此，迫切需要客观的技术，可以定量评估皮肤 炎症和肿瘤在不同的皮肤类型，并可以提供非侵入性替代皮肤 活检宏观光学成像模式可能能够解决这一需求，但主要取决于 基于硅（Si）的光电探测器，这限制了这些设备可以测量的内容，因为在该范围内， 在硅基探测器最灵敏的地方（400-950 nm），黑色素和血红蛋白占主导地位 发色团，而脂质和水基本上不可见。关于显微光学成像 反射共聚焦显微镜（RCM）提供了活检的替代方法。但是常规 RCM仅限于200-350 µm的深度，因此可能会遗漏更深的病变边缘， 延伸到表皮之外的突起是不可接近的。短波红外光谱范围 （900-1700 nm）延伸超出Si基探测器的范围，并且其特征在于增加的水和 脂质吸收和降低的黑色素吸收。在最近的工作中，我们发现非侵入性SWIR成像 提供皮肤炎症的高对比度可视化，可用于获得定量的 炎症指标随疾病进展线性下降。这些考虑告知了 中心假设SWIR成像将支持炎症和肿瘤皮肤的客观评估 无论皮肤色素沉着。在目标1中，我们将开发宏观SWIR成像模式， 测试其在患有以下疾病的患者中的代表性慢性炎症性病症中评估疾病严重程度的能力： 不同的皮肤类型。在目标2中，我们将开发一种显微SWIR成像模式，并测试其超越 现有的光学成像深度限制以及区分良性和恶性病变。这些目标 将通过Shmuylovich实验室的技术专长实现，并在皮肤模拟方面进行临床前验证 随后在人类受试者中进行试点研究。这项工作代表了一个范式转变，在皮肤 成像，从而将新型研究级红外成像转化为临床定量评估 疾病跨越各种皮肤类型的全谱，并且在从全身到全身的长度尺度上 从摄影到虚拟组织学这些新技术将有可能为所有患者提供 获得准确的诊断和皮肤病的管理，提高治疗效果。

Project Summary/Abstract Skin disease affects 1 in 4 Americans and costs $75 billion annually. Diagnosis relies upon visual inspection, but the subjective nature of visual assessment can lead to death from skin cancer misdiagnosis or suffering from misdiagnosis of a treatable chronic inflammatory condition. Non-white Americans make up 40% of the population and face further challenges, because disease can appear more subtly in pigmented skin, leading to systematic underdiagnosis and undertreatment. Skin biopsy is more objective but not all patients, particularly children, tolerate invasive procedures, and there are concerns about overutilization and low diagnostic yield of biopsies. Thus there is an urgent need for objective technologies that can quantitatively assess cutaneous inflammation and neoplasms across diverse skin types, and that can provide noninvasive alternatives to skin biopsy. Macroscopic optical imaging modalities may be able to address this need, but mostly depend on Silicon(Si)-based photodetectors, which constrains what these devices can measure because in the range where Si-based detectors are most sensitive (400-950 nm), melanin and hemoglobin are the dominant chromophores, while lipid and water are essentially invisible. With respect to microscopic optical imaging modalities, reflectance confocal microscopy (RCM) provides an alternative to biopsy. However, conventional RCM is limited to depths of 200-350 µm, and therefore deeper lesion margins may be missed and disease processes that extend beyond the epidermis are inaccessible. The short wave infrared (SWIR) spectral range (900-1700 nm) extends beyond the reach of Si-based detectors, and is characterized by increased water and lipid absorption, and decreased melanin absorption. In recent work we found that noninvasive SWIR imaging provides high contrast visualization of cutaneous inflammation that can be used to derive quantitative measures of inflammation that decrease linearly with disease progression. These considerations inform the central hypothesis that SWIR imaging will support objective assessment of inflammatory and neoplastic skin diseases regardless of skin pigmentation. In Aim 1 we will develop a macroscopic SWIR imaging modality and test its ability to assess disease severity in representative chronic inflammatory conditions in patients with diverse skin types. In Aim 2 we will develop a microscopic SWIR imaging modality and test its ability to surpass existing optical imaging depth limitations and also to differentiate benign from malignant lesions. These aims will be achieved through technical expertise in the Shmuylovich lab, with preclinical validation in skin mimicking phantoms followed by pilot studies in human subjects. This work represents a paradigm shift in cutaneous imaging whereby novel research-grade infrared imaging will be clinically translated to quantitatively assess disease across the full spectrum of diverse skin types, and at length scales ranging from whole body photography to virtual histology. These new technologies will have the potential to provide all patients with access to accurate diagnosis and management of skin disease and improve treatment outcomes.