A key challenge in melanoma diagnosis is the large number of unnecessary biopsies on benign nevi, which requires significant amounts of time and money. To reduce unnecessary biopsies while still accurately detecting melanoma lesions, we propose using Raman spectroscopy as a non-invasive, fast, and inexpensive method for generating a “second opinion” for lesions being considered for biopsy. We collected in vivo Raman spectral data in the clinical skin screening setting from 52 patients, including 53 pigmented lesions and 7 melanomas. All lesions underwent biopsies based on clinical evaluation. Principal component analysis and logistic regression models with leave one lesion out cross validation were applied to classify melanoma and pigmented lesions for biopsy recommendations. Our model achieved an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.903 and a specificity of 58.5% at perfect sensitivity. The number needed to treat for melanoma could have been decreased from 8.6 (60/7) to 4.1 (29/7). This study in a clinical skin screening setting shows the potential of Raman spectroscopy for reducing unnecessary skin biopsies with in vivo Raman data and is a significant step toward the application of Raman spectroscopy for melanoma screening in the clinic.
Raman spectroscopy has shown great potential in detecting nonmelanoma skin cancer accurately and quickly; however, little direct evidence exists on the sensitivity of measurements to the underlying anatomy. Here, we aimed to correlate Raman measurements directly to the underlying tissue anatomy. We acquired Raman spectra of ex vivo skin tissue from 25 patients undergoing Mohs surgery with a fiber probe. We utilized a previously developed biophysical model to extract key biomarkers in the skin from the Raman spectra. We then examined the correlations between the biomarkers and the major skin structures (including the dermis, sebaceous glands, hair follicles, fat, and two types of nonmelanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). SCC had a significantly different concentration of keratin, collagen, and nucleic acid than normal structures, while ceramide differentiated BCC from normal structures. Our findings identified the key proteins, lipids, and nucleic acids that discriminate nonmelanoma tumors and healthy skin using Raman spectroscopy. These markers may be promising surgical guidance tools for detecting tumors in resection margins.
In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of 18 F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.