Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States.
Dartmouth College, Geisel School of Medicine, Hanover, New Hampshire, United States.
J Biomed Opt. 2025 Jan;30(Suppl 1):S13704. doi: 10.1117/1.JBO.30.S1.S13704. Epub 2024 Sep 6.
ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain.
We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography.
A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics.
Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively).
This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
ALA-PpIX 和第二窗口吲哚菁绿 (ICG) 已广泛用于指导高级别胶质瘤的切除。这些药物具有不同的作用机制和摄取特性，这可能会影响它们作为手术指导剂的性能。在接近人脑大小和解剖结构的动物模型中阐明这些差异将有助于指导这些药物的使用。在此，我们报告了使用新型猪脑胶质瘤模型和荧光冷冻断层扫描来评估两种药物在整个大脑中的 3D 分布。
我们旨在使用荧光冷冻断层扫描评估载瘤猪脑中 ALA-PpIX 和第二窗口 ICG 的 3D 空间分布，并进行比较。
通过腺相关病毒递送 Cre 重组酶质粒在转基因 Oncopig 脑中诱导胶质瘤。在肿瘤诱导后，分别在脑收获前 3 小时和 24 小时给予前药 5-ALA 和 ICG。使用荧光冷冻断层扫描对收获的大脑进行成像。使用各种空间分布和对比性能指标在整个大脑中对两种药物的荧光分布进行 3D 评估。
观察到两种药物的空间分布存在显著差异。ICG 聚集在肿瘤核心内，而 ALA-PpIX 则更多地出现在肿瘤边缘。ALA-PpIX 和第二窗口 ICG 均提供了升高的肿瘤与背景对比（分别为 13 和 23）。
这项研究首次展示了使用新型胶质瘤模型和大样本荧光冷冻断层扫描以高分辨率在 3D 中评估和比较成像剂分布。
