Radiation therapy is an important therapeutic modality for thoracic malignancies. However, radiation-induced pulmonary injuries such as radiation pneumonitis and fibrosis are major dose-limiting factors. Previous research shows that micro-computed tomography (micro-CT) can detect radiation-induced lung injuries a few months following irradiation, but studies to assess the early response of lung tissue are lacking. The aim of this study was to determine if micro-CT could be used to detect and assess early-phase radiation–induced lung injury in mice. Twenty-one animals were divided into three groups: normal (n = 7), one day after x-ray exposure (n = 7), and at four days after x-ray exposure (n = 7). The x-ray-exposed groups received a single dose of 20 Gy, to the whole lung. Histology showed enlargements of the air space (Lm: mean chord length) following irradiation. 40.5±3.8 µm and 60.0±6.9 µm were observed after one and four days, respectively, compared to 26.5±3.1 µm in normal mice. Three-dimensional micro-CT images were constructed and histograms of radiodensity - Hounsfield Units (HU) - were used to assess changes in mouse lungs. Radiation-induced lung injury was observed in irradiated mice, by the use of two parameters which were defined as shifts in peak HU between −200 to −800 HU (Peak_HU) and increase in the number of pixels at −1000 HU (Number_-1000). These parameters were correlated with histological changes. The results demonstrate that micro-CT can be used for the early detection and assessment of structural and histopathological changes resulting from radiation-induced lung injury in mice. Micro-CT has the advantage, over traditional histological techniques, of allowing longitudinal studies of lung disease progression and assessment of the entire lung, while reducing the number of animals required for such studies.

Objective: We investigated the use of micro-CT with contrast agent for the non-invasive characterisation of fixed mouse brain tissue specimens as a means to differentiate between grey and white matter. Methods: Nine mice were divided into two groups for micro-CT (n=6) and myelin staining (n=3) experiments. Six mice underwent in vivo micro-CT and were then prepared for brain specimens by transcardiac perfusion with paraformaldehyde. The six mouse brains were soaked in two different concentrations of non-ionic iodinated contrast agents (60 and 150 mg ml−1). Immersion times used for each concentration of iodine were for 3, 7 and 14 days. Three-dimensional ex vivo micro-CT images were acquired with a resolution of 39 μm3 to create isotropic images. The other three mice were stained for evaluation of the myelin structure. Results: Soaking the brains in non-ionic iodinated contrast agent resulted in clear differences in signal between the grey matter, the white matter and the ventricular spaces. The 150 mg ml−1 contrast agent solution yielded images with better contrast-to-noise ratio (CNR) than 60 mg ml−1 iodine contrast agent solution. 14 days of soaking yielded images with better CNR than 3 and 7 days. The CT contrast of grey and white matter derived from the iodine-soaked fixed brains was strongly related to tissue myelin. Conclusion: The present study demonstrated that micro-CT can be used to detect the mouse brain myelin structure at 3, 7 and 14 days after fixation using a CT contrast agent.

Cell tracking with magnetic resonance imaging (MRI) is important for evaluating the biodistribution of transplanted cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a promising therapeutic tool in regenerative medicine. We examined the UC-MSCs labeled with superparamagnetic (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) in terms of cell functioning and imaging efficiency in vitro and in vivo. The UC-MSCs were co-incubated with SPIO or USPIO at a concentration of 50 or 100 µg/mL of label. Viability and proliferation were assessed by Trypan blue dye exclusion and MTT assay, respectively. Differentiation (chondrogenesis, osteogenesis, and adipogenesis) was induced to examine the impact of labelling on stemness. For in vitro experiments, we used 7-T MRI to assess the T₂ values of phantoms containing various concentrations of cell suspensions. For in vivo experiments, nine neonatal rats were divided into the control, SPIO, and USPIO groups. The UC-MSCs were injected directly into the rat brains. MRI images were obtained immediately and at 7 and 14 days post injection. The UC-MSCs were successfully labeled with SPIO and USPIO after 24 h of incubation. Cell viability was not changed by labelling. Nevertheless, labelling with 100 µg/mL USPIO led to a significant decrease in proliferation. The capacity for differentiation into cartilage was influenced by 100 µg/mL of SPIO. MRI showed that labeled cells exhibited clear hypointense signals, unlike unlabeled control cells. In the USPIO-labeled cells, a significant (P < 0.05) decrease in T₂ values (= improved contrast) was observed when compared with the controls and between phantoms containing the fewest and the most cells (0.5 × 10⁶ versus 2.0 × 10⁶ cells/mL). In vivo, the labeled cells were discernible on T₂-weighted images at days 0, 7, and 14. The presence of SPIO and USPIO particles at day 14 was confirmed by Prussian blue staining. Microscopy also suggested that the regions occupied by the particles were not as large as the corresponding hypointense areas observed on MRI. Both labels were readily taken up by the UC-MSCs and identified well on MRI. While SPIO and USPIO provide improved results in MRI studies, care must be taken while labelling cells with high concentrations of these agents.

Magnetic resonance imaging (MRI) is an indispensable diagnostic imaging technique used in the clinical setting. MRI is advantageous over X-ray and computed tomography (CT), because the contrast provided depends on differences in the density of various organ tissues. In addition to MRI systems in hospitals, more than 100 systems are used for research purposes in Japan in various fields, including basic scientific research, molecular and clinical investigations, and life science research, such as drug discovery, veterinary medicine, and food testing. For many years, additional preclinical imaging studies have been conducted in basic research in the fields of radiation technology, medical physics, and radiology. The preclinical MRI research includes studies using small-bore and whole-body MRI systems. In this review, we focus on the animal study using small-bore MRI systems as “preclinical MRI”. The preclinical MRI can be used to elucidate the pathophysiology of diseases and for translational research. This review will provide an overview of previous preclinical MRI studies such as brain, heart, and liver disease assessments. Also, we provide an overview of the utility of preclinical MRI studies in radiological physics and technology.