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Toxicologic Pathology, Vol. 28, No. 1, 100-104 (2000)
DOI: 10.1177/019262330002800112

Virtual Neuropathology: Three-Dimensional Visualization of Lesions Due to Toxic Insult

David S. Lester

Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, Maryland 20708

P. Scott Pine

Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, Maryland 20708

Marielle Delnomdedieu

Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina 27710

Jan N. Johannessen

Division of Toxicological Research, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, Maryland 20708

G. Allan Johnson

Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina 27710

A first-pass approach incorporating high-field magnetic resonance imaging (MRI) was used for rapid detection of neuropathologic lesions in fixed rat brains. This inherently 3-dimensional and nondestructive technique provides high-resolution, high-contrast images of fixed neuronal tissue in the absence of sectioning or staining. This technique, magnetic resonance microscopy (MRM), was used to identify diverse lesions in 2 well-established rat neurotoxicity models. The intrinsic contrast in the images delineated lesions that were identified using a battery of histologic stains, some of which would not be used in routine screening. Furthermore, the MRM images provided the locations of lesions, which were verified upon subsequent sectioning and staining of the same samples. The inherent contrast generated by water properties is exploited in MRM by choosing suitable pulse sequences, or proton stains. This approach provides the potential for a comprehensive initial MRM screen for neurotoxicity in preclinical models with the capability for extrapolation to clinical analyses using classical MRI.

Key Words: Magnetic resonance imaging (MRI) • neurotoxicity • histology • microscopy • rat brain • drug effects


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R. C. Sills, D. L. Morgan, D. W. Herr, P. B. Little, N. M. George, Thai Vu Ton, N. E. Love, R. R. Maronpot, and G. A. Johnson
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[Abstract] [PDF]