R01CA259019

Fast, Large Area, Multiphoton Exoscope (FLAME) for Improving Early Detection of Melanoma - Project Summary

Early detection of melanoma is a key factor in improving patient survival and decreasing treatment costs. The sensitivity of dermoscopy, the standard of care in the diagnosis of melanocytic lesions, was reported to be highly variable, ranging between 68-96%, depending on the proficiency of the physician and the stage of the lesion.

Low sensitivity reflects high rates of false-negative findings, which delay diagnosis and treatment. Thus, doctors must err on the side of caution, which leads to an excess of unnecessary biopsies and increased medical costs.

Distinguishing cutaneous melanoma from benign melanocytic nevi with high accuracy based on dermoscopy remains a challenge even when in the hands of expert clinicians since this approach only offers a two-dimensional image of the lesion's superficial structure.

Ultimately, a biopsy is necessary for definitive diagnosis by the dermatopathologist, but this too may be affected by inter-observer variability, resulting in discordant conclusions.

A study performed at the Melanoma Center at UCSF estimated that 214,500 to 643,500 cases of melanocytic neoplasms in the United States would be diagnosed differently by another dermatopathologist annually, which has significant consequences for the patient regardless of the nature of the lesion.

We propose to develop and clinically evaluate a fast, large area multiphoton exoscope (FLAME) as a tool for non-invasive imaging and early detection of melanoma in order to reduce false positives and false negatives in both dermoscopy and histopathology.

Multiphoton microscopy (MPM) is a nonlinear optical imaging technique that provides unique structural and molecular contrast based on endogenous signals such as second harmonic generation from collagen and two-photon excited fluorescence from NAD(P)H/FAD+, keratin, melanin, and elastin fibers.

In preliminary studies, we demonstrated that macroscopic areas of skin (cm2 scale) could be mapped out with microscopic resolution within ~2 minutes by combining optical and mechanical scanning mechanisms with deep learning image restoration.

As required by PAR-20-155, our academic-industrial partnership will deliver a powerful MPM imaging tool to clinicians for non-invasive, real-time quantitative assessment at the bedside that would not require specialized training.

Our proposed application is for early diagnosis of melanoma, but the approach will have wider impact, for rapid, in vivo characterization of cellular morphologic and metabolic imaging endpoints in patients.

Our specific aims are:
(1) To develop FLAME, a compact, portable MPM prototype system for rapid, depth-resolved in vivo imaging of skin, over macroscopic areas (cm2-scale) with microscopic resolution and enhanced molecular contrast;
(2) To implement safety features and demonstrate the technical feasibility;
(3) To test the performance of FLAME by evaluating its ability to provide in vivo quantitative optical endpoints with sufficiently high predictive power to reliably distinguish benign from early melanoma lesions.

We are a multi-disciplinary team of investigators from UC Irvine, Vidrio Technologies, LLC, and Tufts University with 3 to 8 years' record of collaboration.

Irvine University Of California

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Irvine, California 926173010 United States

Single Zip Code

Academic-Industrial Partnerships (AIP) to Translate and Validate In Vivo Imaging Systems (R01 Clinical Trial Optional) (PAR-20-155)

Amendment Since initial award the total obligations have increased 422% from $593,031 to $3,098,530.