Abstract
BackgroundThere is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report.MethodologyWe performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral infarction and hepatic ischemia. Pathological changes in each lesion were quantified for two weeks by measuring the lesion volume or the ratio of high attenuation area (%HAA), indicative of increased vascular permeability. We also compared brain images of stroke rats and ischemic mice acquired with micro-CT to those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to confirm the diagnosis by CECT.Principal FindingsIn the models of cerebral infarction, vascular permeability was increased from three days through one week after surgical initiation, which was also confirmed by Evans blue dye leakage. Measurement of volume and %HAA of the liver lesions demonstrated differences in the recovery process between mice with distinct genetic backgrounds. Comparison of CT and MR images acquired from the same stroke rats or ischemic mice indicated that accuracy of volumetric measurement, as well as spatial and contrast resolutions of CT images, was comparable to that obtained with MRI. The imaging results were also consistent with the histological data.ConclusionsThis study demonstrates that the CECT scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is also suitable for longitudinal observation of the same animals.
Highlights
Animal models of pathological states, including genetically engineered animals such as transgenic and knockout mice, as well as induced and spontaneous disease models, are valuable for mechanistic studies of similar disorders in humans
This study demonstrates that the contrast-enhanced computed tomography (CT) (CECT) scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is suitable for longitudinal observation of the same animals
The aims of this study were to examine whether i) brain CECT is useful as a non-invasive method with high resolution and accuracy for research on rodent disease models, ii) CECT for small animals is applicable for studies such as serial observation of the same animals and/or diagnosis of lesions in spontaneous disease models, and iii) CECT could potentially be an alternative to conventional histological approaches for diagnosis
Summary
Animal models of pathological states, including genetically engineered animals such as transgenic and knockout mice, as well as induced and spontaneous disease models, are valuable for mechanistic studies of similar disorders in humans These animal models are useful for the rapid screening of pharmaceuticals for action on a target specific to the disease being studied [1]. We have previously studied several pathological rodent models and reported their novel characteristics relevant to the human diseases they model These include stroke-prone spontaneously hypertensive rats (SHRSP) [2], PIT-BD (photochemically induced thrombotic brain damage) mice [3], MCAO (middle cerebral artery occlusion) mice [4], and PIT-LD (photochemically induced thrombotic liver damage) mice [5].
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