Drug toxicity assessment using label-free multimodal nonlinear optical imaging (Conference Presentation)

Aneesh Alex; Jang Hyuk Lee; Jose J. Rico-Jimenez; Eric J. Chaney; Sunish Mohanan; Stephen A. Boppart; Steve R. Hood

doi:10.1117/12.2510032

4 March 2019 Drug toxicity assessment using label-free multimodal nonlinear optical imaging (Conference Presentation)

Aneesh Alex, Jang Hyuk Lee, Jose J. Rico-Jimenez, Eric J. Chaney, Sunish Mohanan, Stephen A. Boppart, Steve R. Hood

Proceedings Volume 10859, Visualizing and Quantifying Drug Distribution in Tissue III; 108590I (2019) https://doi.org/10.1117/12.2510032
Event: SPIE BiOS, 2019, San Francisco, California, United States

Abstract

Pre-clinical toxicology is a statutory requirement of drug development and plays a significant role in reducing attrition in drug discovery. Histopathology and indirect methods such as measurement of toxicity-associated systemic markers in blood or urine samples are the state-of-the-art techniques for toxicity evaluation. Further improvements over these conventional techniques are needed to detect signs of drug-induced toxicity at earlier stages with higher sensitivity and specificity. Multiphoton nonlinear imaging techniques such as two-/three-photon microscopy (2PF/3PF), fluorescence lifetime imaging microscopy (FLIM), second/third harmonic generation (SHG/THG) and coherent anti-Stokes Raman scattering (CARS) microscopy can extract complimentary structural and metabolic information of the target tissue in a label-free manner. In this study, we investigated the capability of a multimodal multiphoton microscopy technique (2PF/3PF/SHG/THG/FLIM/CARS) for detecting both functional and structural changes associated with drug-induced toxicity. Cisplatin, a platinum-based chemotherapy drug, is a cytotoxic agent used to treat many types of cancers. Common side effects of Cisplatin include nephrotoxicity and gonadal dysfunction. We obtained multimodal optical images of organs such as kidney, liver, and testis harvested from mice treated with a single dose of Cisplatin (3mg/kg) by intraperitoneal injection. A control group was treated with 0.9% saline. Structural and metabolic biomarkers related to Cisplatin-induced toxicity were identified and characterized from these multimodal optical images obtained ex vivo. The preliminary results suggest that it may be possible to develop a novel platform for drug toxicity identification and assessment based on multimodal nonlinear optical imaging techniques.

Conference Presentation

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Aneesh Alex, Jang Hyuk Lee, Jose J. Rico-Jimenez, Eric J. Chaney, Sunish Mohanan, Stephen A. Boppart, and Steve R. Hood "Drug toxicity assessment using label-free multimodal nonlinear optical imaging (Conference Presentation)", Proc. SPIE 10859, Visualizing and Quantifying Drug Distribution in Tissue III, 108590I (4 March 2019); https://doi.org/10.1117/12.2510032

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KEYWORDS

Toxicity

Multimodal imaging

Optical imaging

Multiphoton microscopy

Microscopy

Multiphoton fluorescence microscopy

Fluorescence lifetime imaging

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