Application of magnetic resonance imaging in developmental neurotoxicity testing: a pilot study.
In a pilot developmental neurotoxicity study, a protocol was designed to utilize three-dimensional magnetic resonance (MR) images for linear and volumetric measurements of the developing rat brain. MR imaging, because of its non-destructive nature, provides a complement to traditional optical microscopy. Sprague-Dawley dams received 0, 1.25, 4.0 or 7.5mg/kg methylazoxymethanol acetate (MAM) by intraperitoneal injection during gestation days 13-15. At postnatal days (PND) 23 and 60, brains from representative male and female rats from two dams in each dose group were fixed with 10% neutral buffered formalin by transcardial perfusion for in situ MR imaging. A 7T small animal magnet system was used to obtain isotropic images at 100 microm resolution for PND 23 and 150 microm resolution for PND 60. Data from a rapid screening method based on midpoint MR slices of whole brain, cerebrum, cerebellum, and hippocampus showed a dose-related decreased volume of whole brain, cerebrum, and hippocampus in treated rats. Subsequent volumetric estimates using the Cavalieri method confirmed these findings. The brains were subsequently removed and processed for conventional histologic examination of hematoxylin and eosin-stained sections. It is concluded that MR imaging in rat developmental neurotoxicity studies offers the advantages of in situ volumetric measurements of brain structures while preserving the samples for conventional optical microscopy.
Johnson
Kennita
K
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences/NIH/DHHS, 111 Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709, United States. johnso58@niehs.nih.gov
Ryan
Linda
L
Davis
Jeffrey
J
Elmore
Amy
A
Guenther
Brett
B
Marcus
Jill
J
Maronpot
Robert R
RR
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000633:toxicity; D020258:Neurotoxicity Syndromes / Q000175:diagnosis* / Q000209:etiology; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects; D011247:Pregnancy; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D011500:Protein Synthesis Inhibitors; D008746:Methylazoxymethanol Acetate