BACKGROUND Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. METHODS The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin-eosin (HE) stained for comparison with multimodal in vivo imaging. RESULTS The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. CONCLUSIONS The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

中文翻译：

---

用于肿瘤跨病理学研究的多模式活体分子成像系统的概念证明。

背景 跨病理学强调分子成像背后的潜在生理学的解释。然而，由于体内和体外测量之间的差异以及跨尺度图像之间精确配准的困难，它仍然具有挑战性。本研究旨在开发一种多模式活体分子成像 (MIMI) 系统，作为体内肿瘤跨病理学研究的工具。方法 所提出的 MIMI 系统集成了高分辨率正电子成像、磁共振成像 (MRI) 和对无胸腺裸鼠背侧皮肤窗室的显微成像。窗室框架的设计与多模态成像兼容，其基准标记经过定制，可实现模态之间的精确物理对齐。基于带有细导管的体模评估联合配准的准确性。为了验证概念，对人类结直肠腺癌细胞系 HT-29 的肿瘤模型进行了成像。对窗室内的组织进行切片、固定和苏木精-伊红 (HE) 染色，以便与多模式体内成像进行比较。结果 最终的 MIMI 系统的最大视野 (FOV) 为 18 mm × 18 mm。使用基准标记和管道模型，MRI 和正电子成像之间的配准误差为 0.18 ± 0.27 mm，正电子成像和显微成像之间的配准误差为 0.19 ± 0.22 mm，MRI 和显微成像之间的配准误差为 0.15 ± 0.27 mm。一项试点测试表明，MIMI 系统提供了对体内肿瘤微环境的肿瘤解剖、脉管系统和代谢的综合可视化，这与离体病理学一致。结论 建立的多模态活体成像系统提供了一个共同注册的活体平台，用于对成像背后的潜在病理进行跨尺度和透明的研究，具有增强分子成像转化的潜力。