Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE.

Mice are widely used to study arterial disease in humans, and the pathogenesis of arterial diseases is known to be strongly influenced by hemodynamic factors. It is, therefore, of interest to characterize the hemodynamic environment in the mouse arterial tree. Previous measurements have suggested that many relevant hemodynamic variables are similar between the mouse and the human. Here we use a combination of Doppler ultrasound and MRI measurements, coupled with numerical modeling techniques, to characterize the hemodynamic environment in the mouse aortic arch at high spatial resolution. We find that the hemodynamically induced stresses on arterial endothelial cells are much larger in magnitude and more spatially uniform in the mouse than in the human, an effect that can be explained by fluid mechanical scaling principles. This surprising finding seems to be at variance with currently accepted models of the role of hemodynamics in atherogenesis and the known distribution of atheromatous lesions in mice.

Cardiac MR imaging in small animals presents some difficulties due to shorter cardiac cycles and smaller dimensions than in human beings, but prospectively gated techniques have been successfully applied. As with human imaging, there may be certain applications in animal imaging for which retrospective gating is preferable to prospective gating. For example, cardiac imaging in multiple mice simultaneously is one such application. In this work we investigate the use of retrospective gating for cardiac imaging in a mouse. Using a three-dimensional imaging protocol, we show that image quality with retrospective gating is comparable to prospectively gated imaging. We conclude that retrospective gating is applicable for small animal cardiac MRI and show how it can be applied to the problem of cardiac MRI in multiple mice. Magn Reson Med 55:472-477, 2006.

Mouse models are crucial for the study of genetic factors and processes that influence human disease. In addition to tools for measuring genetic expression and establishing genotype, tools to accurately and comparatively assess mouse phenotype are essential in order to characterize pathology and make comparisons with human disease. MRI provides a powerful means of evaluating various anatomical and functional changes and hence is growing in popularity as a phenotypic readout for biomedical research studies. To accommodate the large numbers of mice needed in most biological studies, mouse MRI must offer high-throughput image acquisition and efficient image analysis. This article reviews the technology of multiple-mouse MRI, a method that images multiple mice or specimens simultaneously as a means of enabling high-throughput studies. Aspects of image acquisition and computational analysis in multiple-mouse studies are also described.

With the introduction of mouse models for the study of cardiac morphogenesis, there arises a need for new imaging protocols that can capture both morphological and functional information. High-resolution 2D cardiac cine MRI has often been used to quantify left and right ventricular function. In this study we propose a 3D isotropic cardiac cine MRI protocol with a voxel size of 200 mm 3 as a means of studying cardiac multi-chamber morphology and function. A black blood sequence was used to enhance blood myocardium contrast. Manual segmentation of the ventricles was used to measure ventricular volumes at end diastole and end systole. This method is demonstrated on an Irx4-deficient mouse model. We have been able to identify the volumes of both ventricles dynamically and to show differences in ejection fraction in the mutant. We have also identified an abnormality of the papillary muscle in the mutant that had been missed in previous phenotyping with ultrasound and histology.