Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

Abstract

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.

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

“…Several PET inserts in 7T or 9.4T MRI have been reported, such as Hyperion II and MADPET4 with digital silicon photomultiplier technology ( 41 – 47 ). Recently, Liu et al reported a multimodal intravital imaging system that provided a coregistered in vivo trans- scale and transparent platform (PET, MRI, microscopy) and quantitative evaluation of tumor anatomy, vasculature, and the microenvironment, including glucose, oxygen, and acidity metabolism ( 48 ).…”

CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice

“…The dorsal skinfold window chamber (DSWC) is a model that can be used to directly study the occurrence, progression, and response of drugs to the treatment of living animals, especially for tumor angiogenesis, tumor microenvironment changes, and research on treatment. 27 In 1943, Moy et al first proposed the DSWC, which was fixed by the use of two aluminum chassis in the back of rats through continuous improvement. 28 Presently, the model can be applied to live animals, such as mice, and the fixed frame is also changed from aluminum to titanium or lighter materials.…”

“…Currently, DSWC can also be applied to fluorescence and photoacoustic imaging, ultrasound, magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and multimodal imaging. 27,29,30 Many studies on DSWC have shown the structural and functional differences between tumor blood vessels and normal blood vessels and can quantitatively study tumor blood vessels and normal blood vessel permeability, hemoglobin saturation, and other parameters. In addition, DSWC models enable us to further understand the microcirculation and metabolism of tumors and study living animals at the cellular and molecular levels.…”