Department of Nuclear Medicine, School of Medicine, Technische Universität München, Munich, Germany.
Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China.
Eur J Nucl Med Mol Imaging. 2022 Mar;49(4):1157-1165. doi: 10.1007/s00259-021-05574-y. Epub 2021 Oct 15.
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.
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.
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.
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.
转化病理学强调对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，这仍然具有挑战性。本研究旨在开发一种多模态活体分子成像（MIMI）系统，作为活体肿瘤转化病理学研究的工具。
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）和在无胸腺裸鼠背部皮肤窗口室中的显微镜成像。窗口室框架设计为与多模态成像兼容，其基准标记为模态之间精确物理对准定制。基于具有细导管的体模评估配准精度。为了验证概念，对人结直肠腺癌细胞系 HT-29 的肿瘤模型进行了成像。对窗口室内的组织进行切片、固定和苏木精-伊红（HE）染色，与多模态体内成像进行比较。
最终的 MIMI 系统具有 18mm×18mm 的最大视野（FOV）。使用基准标记和管筒体模，MRI 和正电子成像之间的配准误差为 0.18±0.27mm，正电子成像和显微镜成像之间的配准误差为 0.19±0.22mm，MRI 和显微镜成像之间的配准误差为 0.15±0.27mm。初步试验表明，MIMI 系统提供了对活体肿瘤微环境中肿瘤解剖结构、血管和代谢的综合可视化，与离体病理学一致。
所建立的多模态活体成像系统为跨尺度和透明的成像背后的潜在病理学研究提供了一个配准的体内平台，有潜力增强分子成像的转化。
