MR microscopy of tissues provides a valuable intermediate stage between histology and clinical MRI. Providing 100-1,000 times the spatial resolution of clinical MRI, it facilitates the correlation of MR images with histology. Since MR microscopy has the same contrast properties as clinical imaging, it provides a research tool to better understand the microstructural underpinnings of these properties. This understanding can improve radiologists ability to interpret MR images and guide the development of new MR sequences . In this study we illustrate the use of MR microscopy in liver fibrosis and cirrhosis to improve understanding of MR images, reveal previously MR invisible normal parenchymal microstructure and pathological alterations, and question some prevailing paradigms.

Nine formalin fixed human hepatic specimens (4 normal, 1 stage 2 fibrosis, 1 stage 3 fibrosis, 1 alcoholic cirrhosis, 2 HCV cirrhosis) and two fresh pig liver specimens were examined at 11.7T using a Buker BioSpec 117/16USR animal scanner with a small custom T/R solenoid coil (6 mm diameter). Spin echo (SE), Gradient echo (GRE), Diffusion weighted (DW) images were acquired with the following parameters: 2D SE: TR=3000 TE=8-16ms 40µmx40µmx500µm voxels. 3D GRE: TR=80 FA=15 TE= 312ms 40µmx40µmx500µm voxels. 2D DW SE: TR=2000 TE=16-24ms 100µmx100µmx500µm voxels b=1000-1500 s/mm2 Scan times of 4 to 6 hours. After imaging, specimens were submitted for histology. MR images were analyzed qualitatively, using histology to confirm the observed microstructure.

Normal features The normal hepatic lobule, which is invisible with conventional MRI, was well seen in human tissue MR on both SE and GRE images. The margins of the lobules were of low signal on T2 and T2* weighted images; a signal intensity gradient was observed increasing from the periphery towards the center of the lobule (Fig. 1). Portal venules were seen in the portal triads and hepatic venules were seen centrally. Clotted blood had a high signal intensity on T1 and T2 weighted images. Liquid blood had a high signal on heavily T2 weighted images. Susceptibility effects with changes in signal and intensity and phase were seen with gradient echo images of the portal veins. Susceptibility differences were seen in lobules.

Abnormal Findings Fibrosis alone produced a shortening of T1 and an increase in T2 and T2*. It was concentrated around the portal tracts (Fig. 2). In cirrhosis there was more obvious fibrosis with thickened sheets and irregular nodule formation (Fig. 3). The diffusion weighted images (Fig. 4) showed evidence of anisotropic diffusion, with high signal observed when the diffusion gradient is perpendicular to the plane of fibrosis.

MR microscopy permitted the first ever visualization of the normal human hepatic lobule, providing an anatomic frame of reference for recognizing normal and abnormal features within the liver. The detailed differences within hepatic lobules and the portal tracts have not previously been recognized with MRI in animal or human tissue, nor has the anisotropic nature of fibrosis either in pre-cirrhotic or cirrhotic liver (2,3). The susceptibility changes may reflect normal tissue and abnormal fibrosis as well as effects due to the presence of parenmchymal iron and/or blood products. MR microscopy has the potential to advance our understanding of the MR appearance of the liver and to challenge current paradigms. Ultimately, this information may improve the interpretation of clinical MR images as well as guide the development of MR techniques sensitive to clinically relevant microstructural alterations.