In vivo MR imaging for tumor-associated initial neovascularization by supramolecular contrast agents.

Microvascular imaging is required to understand tumor angiogenesis development; however, an appropriate whole-body imaging method has not yet been established. Here, we successfully developed a supramolecular magnetic resonance (MR) contrast agent for long-term whole-tissue observation in a single individual. Fluorescein- and Gd-chelate-conjugated polyethylene glycols (PEGs) were synthesized, and their structures were optimized. Spectroscopic and pharmacokinetic analyses suggested that the fluorescein-conjugated linear and 8-arm PEGs with a molecular weight of approximately 10 kDa were suitable to form a supramolecular structure to visualize the microvessel structure and blood circulation. Microvascular formation was evaluated in a glioma cell transplantation model, and neovascularization around the glioma tissue at 5 days was observed, with the contrast agent leaking out into the cancer tissue. In contrast, after 12 days, microvessel structures were formed inside the glioma tissue, but the agents did not leak out. These imaging data for the first time proved that the microvessels formed inside cancer tissues at the early stage are very leaky, but that they form continuous microvessels after 12 days.

Application of Magnetic Resonance Strain Analysis Using Feature Tracking in a Myocardial Infarction Model.

This study validates the usefulness of myocardial strain analysis with cardiac cine magnetic resonance imaging (MRI) by evaluating the changes in the cardiac function and myocardial strain values longitudinally in a myocardial disease model. Six eight-week-old male Wistar rats were used as a model of myocardial infarction (MI). Cine images were taken in the short axis, two-chamber view longitudinal axis, and four-chamber view longitudinal axis directions in rats 3 and 9 days after MI and in control rats, with preclinical 7-T MRI. The control images and the images on days 3 and 9 were evaluated by measuring the ventricular ejection fraction (EF) and the strain values in the circumferential (CS), radial (RS), and longitudinal directions (LS). The CS decreased significantly 3 days after MI, but there was no difference between the images on days 3 and 9. The two-chamber view LS was -9.7 ± 2.1% at 3 days and -13.9 ± 1.4% at 9 days after MI. The four-chamber view LS was -9.9 ± 1.5% at 3 days and -11.9 ± 1.3% at 9 days after MI. Both the two- and four-chamber LS values were significantly decreased 3 days after MI. Myocardial strain analysis is, therefore, useful for assessing the pathophysiology of MI.

[Longitudinal In Vivo Evaluation of Knee Osteoarthritis Model Using 7 T-MRI and Micro-CT].

PURPOSE: This study aims to investigate inflammatory changes and osteophyte formation in a rat osteoarthritis (OA) model longitudinally by using 7 T-magnetic resonance imaging (MRI) and micro-computed tomography (CT). METHOD: This OA model is induced surgically by removing the medial collateral ligament and medial meniscus of the right knee joint. Using 7 T-MRI, we compared the relative signal value of the medial collateral site and the area (mm2) of the upper end of the tibia at the right knee joint to those of the left knee joint on T2WI. In addition, we compared statistically the coefficient of variance (CV) of signal intensity on the subchondral bone, the area (mm2), the major axis (mm) and the minor axis (mm) of the upper end of the tibia by the use of micro-CT images. RESULTS: In MRI experiment, the relative signal value was significantly higher at 2, 6, and 10 weeks postoperatively in the medial part of right knee joint than that in the left one. In micro-CT experiment, CV was significantly higher from 6 weeks postoperatively in the subchondral bone of surgical side. Rough and irregular surface at the medial tibia was also observed by 3D images. CONCLUSION: Using 7 T-MRI and micro-CT, we're able to observe the knee osteoarthritis model rat longitudinally.

[In-vivo Evaluation of Bleomycin-induced Lung Fibrosis Model Mouse Using Ultra High-field 7 T-MRI and Micro-CT].

PURPOSE: This study aimed to perform longitudinal observation using 4D-computed tomography (CT) and compare images acquired by 3D-CT and 3D-ultrashort echo time (UTE) for evaluation of bleomycin-induced lung fibrosis model. METHOD: The pulmonary fibrosis model was induced by instilling intratracheally with 50 µl of bleomycin. 4D-CT images were classified into four phases after acquisition and analyzed. To study the effects of respiratory gating, we aquired 3D-CT and 3D-UTE images with and without respiratory gating. For comparison between CT and UTE images, we performed no-triggerd 3D-CT and 3D-UTE under free-breathing. MR signal intensity ratio and CT values were measured in three regions of the upper, middle, and lower lung. RESULTS: At 4DCT, total lung volume at maximum inspiration (4th phase) decreased significantly compared with control mouse and the ratio of lung volume at inspiration to expiration also showed a significant decrease. In comparison of the images between with and without respiratory gating, clearer images were obtained by respiratory gating. However, there was no significant difference between both. In comparison between CT and UTE images, magnetic resonance (MR) signal intensity ratio and CT value were significantly correlated, but 3D-UTE images showed poor delineation of the lower lung and that near the diaphragm compared with 3D-CT images. CONCLUSION: 4D micro-CT and nontriggered 3D UTE-magnetic resonance imaging (MRI) under free breathing can be useful to evaluate bleomycininduced lung fibrosis model mouse.