Magnetic resonance histology

The closing sentence of Paul Lauterbur’s seminal article on magnetic resonance imaging (MRI) states, "Zeugmatographic techniques (imaging) should find many useful applications in studies of internal structures, states and composition of microscopic objects" (1). MRI has revolutionized both clinical medicine and basic science. Few innovations have brought together such widely different disciplines, including chemistry, physics, engineering, radiology, neuroscience, and molecular medicine. In the June 2015 issue of the Journal of Magnetic Resonance Imaging, the article by Pacholczyk-Sienicka et al again demonstrates Professor Lauterbur’s conclusion (2). In "Prediction of survival for patients with advanced colorectal cancer. ," the authors demonstrate a novel analysis of pathology specimens using sophisticated nuclear magnetic resonance (NMR) spectroscopy techniques. The addition of such information to the pathology report improves the clinician’s insight into the "internal composition" of the complex tissue that is cancer. Since the introduction of MRI in the late 1970s, two parallel communities have been pursuing Dr. Lauterbur’s dream. Engineers and radiologists have made enormous progress in advancing MRI technologies and applications for the complex clinical environment. The widespread use of liquid cryogens in the hospital seemed logistically and economically unthinkable in 1975. We have moved from the lowfield (0.15T) resistive magnets of the earliest days of MRI to superconducting 7.0T magnets with selfcontained cryogenic coolers. At the same time, basic scientists pushed spatial resolution into the microscopic domain as early as 1986 (3–5). The resolution in those studies was not sufficient to resolve individual cells, but now even that barrier has fallen. Flint et al recently produced MR images of individual neurons with isotropic resolution at 6.25 mm (6). The voxel volume of these images (244 femtoliters) is more than 4 million times smaller than the voxel of a standard clinical scan (1 mm1⁄41 mL). In addition, there has been frequent exchange between the basic and clinical communities. Diffusion tensor imaging, for example, is based on spectroscopic studies by Stejskal and Tanner (7), amplified by Mosely et al’s imaging observation of neuronal diffusion anisotropy (8) and Basser et al’s development of the diffusion tensor (9). These advances have followed similar paths with initial demonstration of the concept—frequently with technical barriers to routine clinical use. Applications that appear to be totally impractical and of dubious clinical value gradually yield to the combined efforts of basic and clinical scientists, providing greater insight into human tissue and disease. As the spectroscopy study of pathology specimens reported in this issue demonstrates, magnetic resonance histology (MRH) is finding its way into clinical use. We believe that higher-resolution imaging of pathology specimens will have similar benefits. MRH, which is the study of tissue structure using NMR, was proposed in 1993 (10). MRH has found wide use in connecting genotype to phenotype in mouse models (11–13). Furthermore, phenotypic expression, as defined by MRH, has led to identification of human genes through cross-species gene mapping (14). Figure 1 shows a gradient recalled MRH image of an intact adult rat brain acquired at 25-mm isotropic resolution (15). The methods used are now routine in some laboratories. The field of view ( 20 20 40 mm) is comparable to that required for many surgical specimens. The active staining used is also routine and easily translated to the surgical pathology lab (16). While the resolution is not that of an optical microscope, an enormous amount of information is provided in this image. Individual glomerular cells are visible in the olfactory bulb (yellow arrow in the magnified inset). The plexiform and mitral cell layers are also visible in the olfactory bulb (green and blue arrows). Additionally, retinal cell layers are visible in the eye (red arrow). Since