Intraoperative Polarization-Sensitive OCT for Assessing Breast Tumor Margins

项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

KIM, BOKLYE

项目受资助机构

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

项目编号

5R01CA213149-05

立项年度

2021

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

450386.00美元

学科

Bioengineering; Biomedical Imaging; Breast Cancer; Cancer; Clinical Research; Health Disparities; Minority Health; Women's Health;

学科代码

未公开

基金类别

Non-SBIR/STTR RPGs

关键词

未公开

参与者

BOPPART, STEPHEN A

参与机构

NATIONAL CANCER INSTITUTE

项目标书摘要:SUMMARY Breast cancer is a global healthcare burden, not only for the patients diagnosed with this disease, but also their families and friends. The surgical treatment of breast cancer, while successful, has significant limitations that increase patient anxiety, increase costs, and can increase the risk for local recurrence and lifelong post-operative complications. A primary limitation stems from the lack of an intraoperative microscopic assessment of surgical tumor margins. Our cohesive and productive team with academic, clinical, and industrial representation has successfully developed and demonstrated for the first time the use of intraoperative optical coherence tomography (OCT) for in vivo human imaging of tumor margins during breast cancer surgery using a novel handheld surgical imaging probe. Additionally, the development and use of interferometric synthetic aperture microscopy (ISAM) for in vivo imaging has shown an important improvement in resolution and depth-of-field. Despite these advances, challenges remain for identifying tissue microstructure, particularly between normal fibrous stroma and dense tumor tissue, which are both highly scattering structures. To address these challenges, we propose the novel and innovative application of polarization-sensitive OCT (PS-OCT) and PS-ISAM for intraoperative in vivo imaging in human breast cancer surgery, and hypothesize that these will improve the detection sensitivity and specificity of positive breast tumor margins over standard OCT/ISAM. Realizing that the presence and progression of cancer significantly alters the collagen-based tissue microenvironment, the use of PS-OCT to sensitively detect and quantify birefringence of tissue collagen offers the potential for earlier detection of cancer and the altered microenvironment. By leveraging ISAM and other computational optical image segmentation algorithms, we can more fully characterize the tissue/tumor microenvironment. Through four specific aims, we will implement hardware and innovative software contributions to construct an intraoperative multi-mode system capable of real-time OCT/ISAM and PS-OCT/PS-ISAM, then use this system to investigate the performance of these imaging modes in clinical human studies to determine the sensitivity and specificity of ex vivo and in vivo PS-OCT/PS-ISAM over standard OCT/ISAM, and against the standard-of-care assessments which include post-operative histopathology and intraoperative visual/tactile cues. The successful completion of this project is expected to establish the clinical intraoperative use of these new optical imaging techniques, with the goal of reducing the current unacceptably high reoperation rates in the surgical treatment of breast cancer.

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  • 1.Fast fluorescence lifetime imaging microscopy using single- and multiphoton peak event detection for rapid quantification of NAD(P)H-related metabolic dynamics during apoptosis

    • 关键词:
    • Cell culture;Cell death;Computer graphics;Dynamics;Fluorescence imaging;Fluorescence microscopy;Graphics processing unit;Medical imaging;Metabolism;Nucleotides ;Particle beams;Photonics;Photons;Program processors;Tumors;Breast Cancer;Fluorescence lifetime imaging microscopy;Fluorescence lifetimes;In-vivo;Label free;Multiphoton microscopy;Multiphotons;Nicotinamide adenine dinucleotide phosphates;Photon counting;Single photons
    • Sorrells, Janet E.;Marjanovic, Marina;Iyer, Rishyashring R.;Yang, Lingxiao;Chaney, Eric J.;Wang, Geng;Tu, Haohua;Boppart, Stephen A.
    • 《Multiphoton Microscopy in the Biomedical Sciences XXIII 2023》
    • 2023年
    • January 29, 2023 - January 31, 2023
    • San Francisco, CA, United states
    • 会议

    Multiphoton fluorescence lifetime imaging microscopy (FLIM) is used to collect label-free metabolic information from biological samples via autofluorescence lifetime imaging of reduced nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate (NAD(P)H). However, FLIM has traditionally been limited by slow acquisition due to the limited bandwidth of analog electronics that perform photon counting and time-tagging. This slow acquisition has restricted the applicability of multiphoton FLIM of NAD(P)H by impeding the ability to accurately study biological problems that require characterization of fast dynamics. Faster image acquisition can be achieved by directly digitizing the amplified output of a hybrid photodetector and computationally determining photon counts via the Single- and multiphoton PEak Event Detection (SPEED) algorithm. This method, bypassing the limited-bandwidth analog electronics used for photon counting and time-tagging of photons in traditional FLIM, enables fast photon counting capabilities which are well suited for fast, high-dynamic range biological processes such as metabolic changes during apoptosis. Here, we utilize this technology to examine fast dynamics of apoptosis in 2D culture of normal and cancerous human breast cell lines, rat mammary tumor tissue-derived organoids, and in vivo rat mammary tumors. Results indicate that apoptosis-related metabolic dynamics are biological model-dependent and based on local pharmacokinetics, with tumor derived organoids in Matrigel showing a significantly slower response than in vivo or in vitro 2D cell models. Future work should carefully consider these implications when determining which tumor model to use for experimentation and should improve tumor models to better represent in vivo tumor apoptosis dynamics. © 2023 SPIE.

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