Machine Learning and Reflectance Confocal Microscopy for Biopsy-free Virtual Histology of Squamous Skin Neoplasms

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

Document text

Principal Investigator: PHILIP  SCUMPIA
Organization: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
Fiscal Year: 2024
Funding agency: Veterans Affairs

Despite improvements in non-invasive medical imaging to aid in the diagnosis of internal malignancy,
improvements in imaging the skin non-invasively have been slower. The dermatoscope, a device that gives a
magnified and polarized view of the skin, is the only ancillary tool commonly used for clinical assessment by
dermatologists to assist in diagnosis. Keratinocyte carcinomas, basal cell carcinoma and squamous cell
carcinoma, are by far the most common cancers diagnosed in the United States. Due to sun exposure during
military deployment, our nation’s Veterans have an increased likelihood of developing these and other skin
cancers compared to the general population. Early keratinocyte carcinomas are often difficult to distinguish
clinically from irritated/inflamed precancerous or benign skin lesions (actinic or seborrheic keratoses). A non-
invasive technology that can assist dermatologists obtain a diagnosis of skin lesions may prevent unnecessary
biopsy, resulting in fewer scars, as well as allow diagnosis and definitive treatment of skin malignancies in the
same clinic visit, improving clinical workflow and patient access to dermatology clinics. A recently approved
skin imaging technology, reflectance confocal microscopy (RCM), provides state-of-the-art cellular level
resolution of the skin without biopsy, but still has many limitations, limiting its utility to only the most skilled
users. We recently began using software-based digital enhancements to autofluorescence of unstained frozen
tissue sections of microscopic slides to virtually stain unfixed tissue and provide rapid histology quality images
without requiring the laborious tissue processing required of actual processing. Our overarching hypothesis is
that we can apply our digital technology to overcome many of the technical limitations of RCM, and improve
the dermatologists’ or pathologist’s ability to obtain more accurate diagnosis of skin lesion by RCM without
requiring skin biopsy. Our preliminary data demonstrates that our software algorithms can digitally enhance
RCM images of normal skin and basal cell carcinoma, resulting in histologic quality images. In Aim 1, we will
use methodological and computational approaches to refine tissue processing and data acquisition to provide
optimal registration of skin images to obtain the highest quality data sets to train the machine learning
algorithm. In Aim 2, we will incorporate inflamed and uninflamed seborrheic keratosis, actinic keratoses, and
squamous cell carcinoma skin lesions to incorporate features of these lesions into our algorithms originally
developed for normal skin and basal cell carcinoma. In Aim 3, we will perform a pilot study to test the optimized
virtual histology algorithm by prospectively collecting images of consecutive skin lesions on a variety of patient
samples. We will compare how novice and expert RCM dermatology and pathology users perform in obtaining
diagnosis using RCM with and without the virtual histology algorithm. If successful, these studies will provide
an initial step towards noninvasive diagnosis of skin cancer for Veterans and civilians.

Terms: <Accuracy of Diagnosis><Acetic Acids><Actinic (Solar) Keratosis><Actinic keratosis><Adoption><Age><Algorithmic Software><Algorithmic Tools><Algorithms><Architecture><Arizona><Armed Forces Personnel><Basal Cell Epithelioma><Basal Cell Papilloma><Basal cell carcinoma><Basiloma><Benign><Biopsy><Body Tissues><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cancers><Carcinoma Cell><Caring><Cell Communication and Signaling><Cell Signaling><Cicatrix><Clinic><Clinic Visits><Clinical><Clinical assessments><Clinics and Hospitals><Clinics or Hospitals><Color><Communities><Computer software><Cutaneous Disorder><Cutaneous Squamous Cell Carcinoma><Cutaneous malignancy><Data><Data Set><Dermatologic><Dermatologic biopsy><Dermatological><Dermatologist><Dermatology><Dermatoses><Development><Devices><Diagnosis><Doppler OCT><Early Diagnosis><Early treatment><Engineering / Architecture><Enhancement Technology><Epidermis><Epidermoid Carcinoma><Epidermoid Skin Carcinoma><Exposure to><Freezing><Future><General Population><General Public><Generalized Growth><Goals><Growth><Health Care Systems><Healthcare Systems><Histologic><Histologically><Histology><Image><Imaging Device><Imaging Instrument><Imaging Tool><Imaging technology><Individual><Intracellular Communication and Signaling><Intraepidermal Nevus><Intraepidermal Nevus of the Skin><Junction Nevus><Junctional Melanocytic Nevus><Junctional Melanocytoma><Junctional Nevus><Junctional Skin Nevus><Keratinocyte carcinoma><Keratinocyte tumor><Keratosis Seborrheica><Lesion><Libraries><Licensing><Life><Machine Learning><Malignant><Malignant - descriptor><Malignant Epithelial Cell><Malignant Keratinocyte><Malignant Neoplasms><Malignant Skin Neoplasm><Malignant Tumor><Medical Care Costs><Medical Imaging><Methodology><Microscopic><Military><Military Personnel><Neoplasms><Non-Melanoma Skin Cancer><Nuclear><OCT Tomography><Optical Coherence Tomography><Output><Pathologist><Pathology><Patient Care><Patient Care Delivery><Patients><Pilot Projects><Planocellular Carcinoma><Procedures><Resolution><Risk><Rodent Ulcer><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Scanning><Scars><Seborrheic keratosis><Senile Hyperkeratosis><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Signal Transduction><Signal Transduction Systems><Signaling><Skin><Skin Cancer><Skin Carcinoma><Skin Diseases><Skin Diseases and Manifestations><Skin Malignancy><Skin Neoplasms><Skin Tumor><Slide><Software><Software Algorithm><Solar Keratosis><Squamous Carcinoma><Squamous Cell Epithelioma><Squamous cell carcinoma><Staining method><Stains><Sun Exposure><Techniques><Technology><Testing><Time><Tissue Growth><Tissue Stains><Tissues><Training><Triage><United States><Universities><Veterans><Visit><Wait Time><Work><accurate diagnosis><adversarial neural network><ages><biological signal transduction><cancer diagnosis><care for patients><care of patients><caring for patients><computer imaging><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><cost><cutaneous biopsy><cutaneous disease><data acquisition><data acquisitions><data to train><dataset to train><deep learning><deep learning algorithm><deep learning method><deep learning strategy><dermal disease><dermal disorder><developmental><diagnosis evaluation><diagnostic accuracy><digital><digital imaging><digital technology><early detection><early therapy><generative adversarial network><generative neural network><histologic image><histologic stains><histological image><histological stains><image-based method><imaging><imaging method><imaging modality><improved><in vivo><in vivo confocal microscopy><irritation><keratinocyte><machine based learning><machine learned algorithm><machine learning algorithm><machine learning based algorithm><malignancy><malignant skin tumor><medical costs><medical expenses><microscope imaging><microscopic imaging><microscopy imaging><military member><military population><military service><multiphoton excitation microscopy><multiphoton microscopy><neoplasia><neoplasm/cancer><neoplastic growth><non-invasive diagnosis><non-invasive diagnostic><noninvasive diagnosis><noninvasive diagnostic><nonmelanoma skin cancer><novel><ontogeny><optical Doppler tomography><optical coherence Doppler tomography><pilot study><portability><precancer><precancerous><premalignant><prevent><preventing><prospective><reflectance confocal microscopy><resolutions><senile keratosis><service member><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><skills><skin biopsy><skin disorder><skin lesion><skin squamous cell carcinoma><solar exposure><sun light exposure><sun protection><sunlight exposure><tech development><technology development><teledermatology><telehealth><tissue processing><tool><training data><uptake><virtual>