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.

Project Narrative: Skin disease affects 1 in 4 Americans, and doctors base diagnosis and management decisions on changes in skin appearance. But visual markers of disease can be indirect and subjective, especially in skin of color patients where skin changes like redness are harder to see. We propose new infrared imaging technology that allows skin disease to be more objectively measured at both large and microscopic scales.