Contrast mechanisms in pump-probe microscopy of melanin.

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2022-08

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Abstract

Pump-probe microscopy of melanin in tumors has been proposed to improve diagnosis of malignant melanoma, based on the hypothesis that aggressive cancers disaggregate melanin structure. However, measured signals of melanin are complex superpositions of multiple nonlinear processes, which makes interpretation challenging. Polarization control during measurement and data fitting are used to decompose signals of melanin into their underlying molecular mechanisms. We then identify the molecular mechanisms that are most susceptible to melanin disaggregation and derive false-coloring schemes to highlight these processes in biological tissue. We demonstrate that false-colored images of a small set of melanoma tumors correlate with clinical concern. More generally, our systematic approach of decomposing pump-probe signals can be applied to a multitude of different samples.

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10.1364/oe.469506

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Grass, David, Georgia M Beasley, Martin C Fischer, M Angelica Selim, Yue Zhou and Warren S Warren (2022). Contrast mechanisms in pump-probe microscopy of melanin. Optics express, 30(18). pp. 31852–31862. 10.1364/oe.469506 Retrieved from https://hdl.handle.net/10161/31811.

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Scholars@Duke

Grass

David Grass

Research Associate

I'm a postdoctoral associate in the department of Chemistry at Duke University. My primary interests are light-matter interactions at the nano- and micro-scale. My main research focus at the moment is improving diagnosis of cutaneous melanoma with advanced microscopic methods (pump-probe microscopy). More broadly, I am also interested in optical levitation and it's application to fundamental physics, i.e. macroscopic quantum physics, as well as sensing.

Beasley

Georgia Marie Beasley

Associate Professor of Surgery

Dr. Beasley is an associate professor of surgery in the division of Surgical Oncology at Duke University with a secondary appointment as associate professor in the department of medicine.  After playing 3 years in the women’s NBA, she began medical school. She obtained her MD (2008) and Masters of Health Science in clinical research (2010) from Duke University School of Medicine.  She then completed general surgical residency at Duke University in 2015, during which time she was awarded a traineeship under a long-standing Surgical Oncology T32 grant. She then completed a fellowship in complex surgical oncology at the Ohio State University in 2017. She returned to Duke in 2017 as a faculty member. In 2019, she became co-director of the Duke Melanoma Program.

Dr. Beasley is a surgeon scientist with active involvement in clinical and translational research. Her main clinical and research interests include immunologic aspects of melanoma including oncolytic viral therapy.  She is principal investigator of over 10 therapeutic clinical trials in melanoma including novel intratumoral therapies. Her research focuses on the role of innate immunity in the anti-tumor response. She has authored over 100 publications centered on melanoma. She has received multiple internal and external funding including the Society of Surgical Oncology’s Young Investigator Award, NIH K08 mentored physician scientist award, and Melanoma Research Alliance Grant..  Most recently she was selected to Duke Medical School’s Alpha Omega Alpha and received the American Society for Clinical Investigation Young Physician-Scientist Award.

 

Fischer

Martin Fischer

Research Professor in the Department of Chemistry

Dr. Fischer’s research focuses on exploring novel nonlinear optical contrast mechanisms for molecular imaging. Nonlinear optical microscopes can provide non-invasive, high-resolution, 3-dimensional images even in highly scattering environments such as biological tissue. Established contrast mechanisms, such as two-photon fluorescence or harmonic generation, can image a range of targets (such as autofluorescent markers or some connective tissue structure), but many of the most molecularly specific nonlinear interactions are harder to measure with power levels one might be willing to put on tissue. In order to use these previously inaccessible interactions as structural and molecular image contrasts we are developing ultrafast laser pulse shaping and pulse shape detection methods that dramatically enhance measurement sensitivity. Applications of these microscopy methods range from imaging biological tissue (mapping structure, endogenous tissue markers, or exogenous contrast agents) to characterization of nanomaterials (such as graphene and gold nanoparticles). The molecular contrast mechanisms we originally developed for biomedical imaging also provide pigment-specific signatures for paints used in historic artwork. Recently we have demonstrated that we can noninvasively image paint layers in historic paintings and we are currently developing microscopy techniques for use in art conservation and conservation science.

Dr. Fischer is also the director of the Advanced Light Imaging and Spectroscopy (ALIS) facility at Duke University.

Warren

Warren S. Warren

James B. Duke Distinguished Professor of Chemistry

Our work focuses on the design and application of what might best be called novel pulsed techniques, using controlled radiation fields to alter dynamics. The heart of the work is chemical physics, and most of what we do is ultrafast laser spectroscopy or nuclear magnetic resonance. It generally involves an intimate mixture of theory and experiment: recent publications are roughly an equal mix of pencil- and-paper theory, computer calculations with our workstations, and experiments. Collaborations also play an important role, particularly for medical applications.


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