Detection of Myocardial Capillary Orientation With Intravascular Iron-Oxide Nanoparticles in Spin-Echo MRI

In mammalian hearts the capillaries are closely aligned with the muscle fibers. We report our observation of a main-field direc- tion-dependent contrast in MR spin-echo (SE) images of the heart in the presence of Ferumoxtran-10, an intravascular iron- oxide nanoparticle contrast agent (CA). We describe a novel MRI method for mapping the preferential orientation of capil- laries in the myocardial wall. The eigenvector corresponding to the minimum eigen value of the R2 relaxation rate tensor is consistent with the expected orientation of the capillary net- work. Preliminary results also demonstrate the feasibility of this method for in vivo application to rodent imaging. Magn Reson Med 55:725-730, 2006. Published 2006 Wiley-Liss, Inc. † The transmural helical structure of the myofibers in the heart and the consequent contraction pattern has been known for centuries (1-3), and so has the fact that the capillaries are closely aligned with the muscle fibers (3). We report our observations of a main magnetic field, B0, direction-dependent contrast in MR spin-echo (SE) images of the heart in the presence of intravascular iron-oxide nanoparticles. The main external field direction depen- dence makes it possible to calculate the tensor compo- nents of the direction-dependent transverse relaxation rate (R2 or 1/T2). The tertiary principal direction of the R2 tensor coincides with the capillary orientation within the myocardial wall, and the correlation between the two can be explained by the physics of proton spin relaxation around the mostly parallel capillary vessels. The nanoparticle contrast agent (CA) Ferumoxtran-10 is an aqueous solution that contains magnetite crystalline cores that are coated with dextran. They are too large to move across the pores of the endothelium of the capillaries and thus are confined to the intravascular space while they are slowly absorbed by the reticuloendothelial system of the liver. Because of their superparamagnetic nature they are fully magnetized in the field of a 1.5 Tesla MRI scanner (4), and create strong, heterogeneous, and localized fields around capillary vessels. In SE imaging, proton spins of tissue water undergo diffusive Brownian motion in these induced fields that accelerates T2 relaxation. In the heart the capillaries are morphologically nearly parallel tubes that are aligned with the muscle fibers, and the field pat- tern around such a capillary is highly dependent on its orientation relative to the external main field (5), as illus- trated in Fig. 1. The strongest local field gradients occur when the capillary is perpendicular to the main field, and as demonstrated by Monte-Carlo simulations of a capillary lattice in the heart (6), this condition should create the maximum T2 relaxation and the lowest signal level in SE images. We observed in both beating hearts and excised heart samples this variation of SE image intensity with orienta- tion, as well as heterogeneous image intensity in the myo- cardial wall. We ruled out other potential instrumentation factors that might cause such heterogeneity with control images acquired using short echo times (TEs) and thus minimal T2 relaxation. To characterize the directional de- pendence in the R2 relaxation rate, we derived the second- order R2 tensor from a set of images of an excised heart sample. A map of the tertiary eigenvector of the tensor, indicating the direction of minimum R2, was then plotted throughout the myocardial wall. The results can be fully explained by the anisotropic R2 relaxation in the presence of largely parallel capillaries, in the light of the well- known transmural helical patterns of the myofiber and capillary orientation of the heart (2) (i.e., the direction of minimum R2 relaxation coincides with the myofiber ori- entation in all locations of the heart). This observation provides a robust means of mapping the capillary orientation in vivo with simple SE imaging, and reducing susceptibility to physiological motion due to the lack of large motion-encoding gradients.