Myocarditis is a potentially lethal inflammatory heart disease of children and young adults that frequently leads to dilated cardiomyopathy (DCM). Since diagnostic procedures and efficient therapies are lacking, it is important to characterize the critical immune effector pathways underlying the initial cardiac inflammation and the transition from myocarditis to DCM. We describe here a T-cell receptor (TCR) transgenic mouse model with spontaneously developing autoimmune myocarditis that progresses to lethal DCM. Cardiac magnetic resonance imaging revealed early inflammation-associated changes in the ventricle wall including transient thickening of the left ventricle wall. Furthermore, we found that IFN-γ was a major effector cytokine driving the initial inflammatory process and that the cooperation of IFN-γ and IL-17A was essential for the development of the progressive disease. This novel TCR transgenic mouse model permits the identification of the central pathophysiological and immunological processes involved in the transition from autoimmune myocarditis to DCM.

A cryogenic 200-MHz RF transmit/receive probe (CryoProbe) made of copper and designed for murine brain studies is described. The probe operates at 30K and its performance was compared to a home-made surface coil of equal dimensions and a mouse head volume resonator, both operating at room temperature (RT). Since for small volumes of tissue interrogated (<5 mL) sample noise and thermal noise of the receiver are of comparable magnitude, considerable noise reduction can be achieved by cooling of the receiver system, e.g., using cold helium gas. The effect of temperature lowering on the signal-to-noise ratio (SNR) was assessed in phantom and in vivo murine brain studies using conventional MRI sequences (spin and gradient echo) and single voxel MR spectroscopy. Consistent sensitivity increases were observed for the CryoProbe. SNR increases by a factor ≥2 for the phantom experiments and by factors of 1.8 to 1.9 for in vivo experiments when compared to the RT surface coil for both MRI and MRS experiments. These results are in good agreement with estimated SNR gains for a circular surface coil probe cooled to 30K. The use of a cryogenic probe represents an economically attractive option to enhance the sensitivity in small animal MRI/MRS.

Amyloid-␤ (A␤) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcA␤ model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-MRA). Three-dimensional gradient echo datasets with 60 m isotropic resolution were acquired in 4-and 24-month-old arcA␤ mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-MRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 m) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20 -80 m) has been observed in 24-month-old arcA␤ mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and A␤ deposition in small-and medium-sized vessels, but not in large cerebral arteries, of 24-monthold arcA␤ mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of A␤ and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-MRA in mice.