衰减和后向散射系数的双参数层析成像定量评价免疫细胞介导的肿瘤球体细胞毒性。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-22 eCollection Date: 2025-01-01 DOI:10.7150/thno.118722
Seokgyu Han, Ingyoung Kim, Baekcheon Seong, Woovin Kim, Hongseong Kim, Sein Kim, Chulmin Joo, Sungsu Park
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引用次数: 0

摘要

理由:由于缺乏实时无标记分析工具,免疫细胞介导的肿瘤球体细胞毒性的定量、非扰动评估仍然具有挑战性。传统的方法,如荧光成像或生化分析往往需要标记和提供有限的纵向分析,这禁止动态监测治疗反应。本研究提出了一种双参数层析分析方法,该方法同时量化光学相干断层扫描(OCT)数据集的衰减系数(AC)和后向散射系数(BSC),从而能够动态评估三维(3D)肿瘤球体的治疗反应。方法:我们开发了一种基于3D Gabor变换的算法,从OCT体积数据集中提取深度分辨AC和BSC指标。与传统策略不同,我们的方法能够同时测量AC和BSC值的体素,具有优越的噪声鲁棒性。脂质内溶液在不同浓度范围内的实验表明,基于gabor的方法产生的AC和BSC估计精度比以前的方法高三倍以上。这种方法能够高分辨率地测量与细胞凋亡相关的结构和光学特性变化,允许在用AZD4547和her2靶向嵌合抗原受体(CAR) T细胞治疗的her2阳性乳腺肿瘤球体中进行空间和时间定位。结果:azd4547处理的球体,AC呈剂量依赖性增加,从0.39增加到0.64,增加了64%;BSC从0.09增加到0.12,增加了约33%。CAR - T细胞治疗诱导AC和BSC的快速、空间进行性增加,起源于球体周围并向内推进。12 h后,AC从0.40增加到0.82(增加2倍),BSC从0.09增加到0.20(增加2.2倍)。虽然AC和BSC单独与球体活力相关,但它们的综合分析一致地在两种处理方式中获得更高的决定系数(R²= 0.98)。结论:这种基于oct的双参数检测框架为区分免疫和药物诱导的肿瘤球体细胞凋亡提供了一种敏感、无标记的方法。它与生存能力和解决空间分解动力学的能力强相关,强调了它在免疫治疗疗效的原位评估方面的强大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dual-parameter tomographic imaging of attenuation and backscattering coefficients for quantitative evaluation of immune cell-mediated cytotoxicity in tumor spheroids.

Rationale: Quantitative, non-perturbative assessment of immune cell-mediated cytotoxicity in tumor spheroids remains challenging due to the lack of real-time label-free analytical tools. Conventional methods such as fluorescence imaging or biochemical assays often require labeling and provide limited longitudinal analysis, which prohibits dynamic monitoring of therapeutic responses. This study presents a dual-parameter tomographic analysis method that simultaneously quantifies attenuation coefficient (AC) and backscattering coefficient (BSC) from optical coherence tomography (OCT) datasets, enabling dynamic evaluation of therapeutic responses in three-dimensional (3D) tumor spheroids. Methods: We developed a 3D Gabor transform-based algorithm to extract depth-resolved AC and BSC metrics from OCT volumetric datasets. Unlike conventional strategies, our method enables simultaneous voxel-wise measurements of AC and BSC values, with superior noise robustness. Experiments with intralipid solutions across a range of concentrations revealed that the Gabor-based approach yielded AC and BSC estimations with more than three times greater precision than prior methods. This approach enables high-resolution measurements of structural and optical property changes associated with apoptosis, allowing spatial and temporal mapping of treatment-induced cytotoxicity in HER2-positive breast tumor spheroids treated with AZD4547 and HER2-targeted chimeric antigen receptor (CAR) T cells. Results: In AZD4547-treated spheroids, AC increased dose-dependently from 0.39 to 0.64, reflecting a 64% rise, while BSC increased from 0.09 to 0.12, an approximate 33% increase. CAR T cell treatment induced a rapid, spatially progressive increase in both AC and BSC, originating at the spheroid periphery and advancing inward. Over 12 hours, AC rose from 0.40 to 0.82 (2-fold increase) and BSC from 0.09 to 0.20 (2.2-fold increase). While AC and BSC individually correlated with spheroid viability, their combined analysis consistently achieved a higher coefficient of determination (R² = 0.98) across both treatment modalities. Conclusions: This dual-parameter OCT-based assay framework provides a sensitive, label-free method for distinguishing between immune- and drug-induced apoptosis in tumor spheroids. Its strong correlation with viability and capacity to resolve spatially resolved dynamics underscore its potential for robust, in situ assessment of immunotherapeutic efficacy.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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