Application of a compact magnetic resonance imaging system for toxicologic pathology: evaluation of lithium-pilocarpine-induced rat brain lesions

Abstract

Magnetic resonance imaging (MRI) is a useful noninvasive tool used to detect lesions in clinical and veterinary medicine. The present study evaluated the suitability of a new easy-to-use compact MRI platform (M2 permanent magnet system, Aspect Imaging, Shoham, Israel) for assisting with preclinical toxicologic pathology examination of lesions in the rat brain. In order to induce brain lesions, male Sprague-Dawley rats were treated once with lithium chloride (127 mg/kg, intraperitoneal [i.p.]) followed by pilocarpine (30 mg/kg, i.p.). One week after dosing, the perfused, fixed brains were collected, analyzed by the MRI system and examined histopathologically. MRI of the brain of treated rats revealed areas of high T1 and middle to low T2 signals, when compared with the controls, in the piriform cortex, lateral thalamic nucleus, posterior paraventricular thalamic nucleus and posterior hypothalamic nucleus of the cerebrum. The altered MRI signal areas were consistent with well-circumscribed foci of neuronal cell degeneration/necrosis accompanied by glial cell proliferation. The present data demonstrated that quick analysis of fixed organs by the MRI system can detect the presence and location of toxicologic lesions and provide useful temporal information for selection of appropriate sections for histopathologic examination before routine slide preparation, especially in complex and functionally heterogeneous organs such as the brain.

In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources

“…Lower bottom inset shows terminal deoxynucleotidyl transferase dUTP nick-end labeled (TUNEL)-positive apoptotic cells in F (brown nuclear staining), while TUNEL-staining is negative in the inset of photo E. Taketa T, et al with permission. 102 stays intact and can be used for conventional histopathology evaluation, which can be better directed based on the results of the MRI images. Furthermore, ex vivo MRI scans can also provide important information on the structure and volume of the lesions,while also providing information on the effects on adjacent, seemingly unaffected tissue.…”

Regulatory Forum Opinion Piece*: Imaging Applications in Toxicologic Pathology—Recommendations for Use in Regulated Nonclinical Toxicity Studies

“…Inset: (E) terminal deoxynucleotidyl transferase dUTP nickend labeled (TUNEL) negative staining and (F) TUNEL positive staining. Source: Reprinted with permission of Taketa et al (2015). phantoms for each specific type of imaging will be needed to ensure proper functioning of imaging equipment and to confirm the accuracy, sensitivity, and precision of specific imaging protocols.…”

“…In a second neurotoxic model, IP administration of lithium chloride (127 mg/kg) was followed by IP administration of pilocarpine (30 mg/kg) to produce a status epilepticus model in the rat (Taketa et al 2015). One week after dosing, the perfused, fixed brains were collected, imaged using the compact MRI, and examined histopathologically.…”

“…Inset: (E) terminal deoxynucleotidyl transferase dUTP nick-end labeled (TUNEL) negative staining and (F) TUNEL positive staining. Source : Reprinted with permission of Taketa et al (2015).…”

Development of a non-invasive method for testicular toxicity evaluation using a novel compact magnetic resonance imaging system

“…With progress in design technology, a novel compact MRI system with a high-field permanent magnet (∼1.0 tesla) has been developed to reduce the cost and complexity of superconducting magnets for MRI systems (Taketa et al, 2015, Pittala et al, 2018, Daneshgaran et al, 2019). The new system is portable and self-shielded; it can be placed in most institutions.…”