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Browsing by Author "Kim, Young L."
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Item Data-driven imaging of tissue inflammation using RGB-based hyperspectral reconstruction toward personal monitoring of dermatologic health(Optical Society of America, 2017-10-26) Kim, Taehoon; Visbal-Onufrak, Michelle A.; Konger, Raymond L.; Kim, Young L.; Pathology and Laboratory Medicine, School of MedicineSensitive and accurate assessment of dermatologic inflammatory hyperemia in otherwise grossly normal-appearing skin conditions is beneficial to laypeople for monitoring their own skin health on a regular basis, to patients for looking for timely clinical examination, and to primary care physicians or dermatologists for delivering effective treatments. We propose that mathematical hyperspectral reconstruction from RGB images in a simple imaging setup can provide reliable visualization of hemoglobin content in a large skin area. Without relying on a complicated, expensive, and slow hyperspectral imaging system, we demonstrate the feasibility of determining heterogeneous or multifocal areas of inflammatory hyperemia associated with experimental photocarcinogenesis in mice. We envision that RGB-based reconstructed hyperspectral imaging of subclinical inflammatory hyperemic foci could potentially be integrated with the built-in camera (RGB sensor) of a smartphone to develop a simple imaging device that could offer affordable monitoring of dermatologic health.Item Evidence for a non-stochastic two-field hypothesis for persistent skin cancer risk(Nature, 2020-11-05) Konger, Raymond L.; Ren, Lu; Sahu, Ravi P.; Derr-Yellin, Ethel; Kim, Young L.; Dermatology, School of MedicineWith recurring carcinogen exposures, individual tumors develop in a field of genetic mutations through a stepwise process of clonal expansion and evolution. Once established, this “cancer field” persists in the absence of continued carcinogen exposures, resulting in a sustained risk for cancer development. Using a bioimaging approach, we previously demonstrated that a dermal premalignant field characterized by inflammatory angiogenesis persists following the cessation of ultraviolet light exposures and accurately predicts future overlying epidermal tumor formation. Following ultraviolet light treatments, others have observed that patches of p53 immunopositive cells persist stochastically throughout the epidermal stem cell population. However, these studies were done by random biopsies, introducing sampling bias. We now show that, rather than being randomly distributed, p53+ epidermal cells are enriched only in areas overlying this multi-focal dermal field. Moreover, we also show that the dermal field is characterized by a senescent phenotype. We propose that persistence of the overlying epithelial cancerization field in the absence of exogenous carcinogens or promoters requires a two-field composite consisting of a dermal senescent field driving the persistence of the overlying epidermal cancer field. These observations challenge current models that suggest that persistence of cancer risk in the absence of continued carcinogen exposures is simply a function of stochastically arranged, long-lived but dormant epithelial clonal stem cells mutants. The model proposed here could provide new insights into how cancer risk persists following cessation of carcinogenic exposures.Item Large area, label-free imaging of extracellular matrix using telecentricity(SPIE, 2017-01) Onufrak, Michelle A. Visbal; Konger, Raymond L.; Kim, Young L.; Pathology and Laboratory Medicine, School of MedicineSubtle alterations in stromal tissue structures and organizations within the extracellular matrix (ECM) have been observed in several types of tissue abnormalities, including early skin cancer and wounds. Current microscopic imaging methods often lack the ability to accurately determine the extent of malignancy over a large area, due to their limited field of view. In this research we focus on the development of simple mesoscopic (i.e. between microscopic and macroscopic) biomedical imaging device for non-invasive assessment of ECM alterations over a large, heterogeneous area. In our technology development, a telecentric lens, commonly used in machine vision systems but rarely used in biomedical imaging, serves as a key platform to visualize alterations in tissue microenvironments in a label-free manner over a clinically relevant area. In general, telecentric imaging represents a simple, alternative method for reducing unwanted scattering or diffuse light caused by the highly anisotropic scattering properties of biological tissue. In particular, under telecentric imaging the light intensity backscattered from biological tissue is mainly sensitive to the scattering anisotropy factor, possibly associated with the ECM. We demonstrate the inherent advantages of combining telecentric lens systems with hyperspectral imaging for providing optical information of tissue scattering in biological tissue of murine models, as well as light absorption of hemoglobin in blood vessel tissue phantoms. Thus, we envision that telecentric imaging could potentially serve for simple site-specific, tissue-based assessment of stromal alterations over a clinically relevant field of view in a label-free manner, for studying diseases associated with disruption of homeostasis in ECM.Item Mapping Cutaneous Field Carcinogenesis of Nonmelanoma Skin Cancer Using Mesoscopic Imaging of Pro-inflammation Cues(Wiley, 2024) Shugar, Andrea L.; Konger, Raymond L.; Rohan, Craig A.; Travers, Jeffrey B.; Kim, Young L.; Pathology and Laboratory Medicine, School of MedicineNonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.