Background
Increased tissue stiffness (also termed modulus) has been shown to be a characteristic of potential tumor metastasis. Measured values of the stiffness of tumors and cancer cells are reported in the literature to increase compared to neighboring normal tissues. Yet the relationship between the mechanical properties of cells and the extracellular matrix has yet to be correlated with the histopathology of cancerous lesions.
Materials and Methods
We have developed a technique to do virtual biopsies of skin lesions by combining images made using optical coherence tomography with stiffness measurements made simultaneously using vibrational analysis. The technique is termed vibrational optical coherence tomography (VOCT).
Results
In this paper, we report that precancerous and cancerous lesions are characterized by changes in both the morphology and stiffness of the cellular components of the skin. The ratio of the peak heights that correspond to the epidermal (40‐60Hz) and dermal (140‐160 Hz) resonant frequencies appear to be different for benign and cancerous or precancerous lesions compared with normal skin and scar.
Conclusions
Cell‐to‐cell and epidermal‐to‐dermal interactions may be very important in evaluating the potential of skin lesions to become malignant. These interactions can be evaluated using VOCT, a new technique for performing “virtual biopsies” of skin lesions.
Previous literature reports suggest that tissue stiffness is a predictor of cancer and metastatic behavior. We have used optical coherence tomography and vibrational analysis (VOCT) to characterize normal skin, scar and a verrucous carcinoma, a squamous cell carcinoma subtype, non-invasively and nondestructively. The results suggest that epidermal thickening and increased keratin production occur in verrucous carcinoma and lead to increases in surface hills and valleys as well as subsequent increases in epidermal stiffness values. Increased stiffness of the epidermis is a result of increased keratin production while the stiffness of the dermis remains similar to that of normal skin, suggesting that dermal changes are not observed in this lesion. It is concluded that VOCT may ultimately be a useful adjunct to dermoscopy and other clinical tools to identify and characterize lesions as small as 0.2 mm. It is hypothesized that the slow growth potential of verrucous carcinoma may be related to the lack of dermal involvement and that other more invasive skin lesions may be characterized by both epidermal and dermal involvement that would lead to changes in both epidermal and dermal stiffnesses.
Tissue biopsies and implant analysis during animal testing or clinical studies are a requirement for development of new surgical materials and procedures. In this paper we report the use of vibrational OCT (VOCT) to evaluate the viscoelastic behavior of tissues, polymeric materials, biofilms, and viscoelastic solutions of macromolecules. Our results suggest that VOCT is a useful technique to characterize the behavior of cellular tissues and biofilms, polymeric implant materials and viscoelastic solutions used in medicine. It is demonstrated that the modulus and resonant frequency squared per unit thickness is a feature that can be used to characterize a variety of tissues. Further work is needed to understand the generalized behavior of synthetic polymers and viscoelastic solutions.
Background
The modulus and resonant frequency of cancer cells and extracellular matrix are increased in both basal cell and squamous cell carcinomas, and in addition, the collagen stiffness is increased. The organization of the extracellular matrix surrounding cancer cells is clearly different than the extracellular matrix that is seen in normal skin.
Materials and Methods
We have used vibrational optical coherence tomography (VOCT) to measure the resonant frequency and stiffness of collagen, vascular, and reorganized fibrous extracellular matrix components. Measurements of vessels and fibrotic collagen content made on basal cell carcinomas (BCCs) are compared to similar measurements made on normal skin from different anatomical locations.
Results
Lesions with basal cell carcinomas exhibit characteristic resonant frequencies and moduli of reorganized extracellular matrix characteristic of fibrotic tissue. Cancerous lesions are characterized by dermal collagen (100 Hz), vascular (150 Hz), and fibrotic peaks (200‐230 Hz). The fibrotic peak is not found in areas of normal skin.
Conclusions
Based on this pilot study, it is hypothesized inflammation may promote precancerous lesion formation in the surrounding extracellular matrix. Measurement of the increases in vaculature and fibrotic content may be useful in early detection of BCCs.
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