Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans

Background: More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure relative to matched, unexposed GW veterans estimated from 1.5 T magnetic resonance images (MRI). Here we investigate, in a different cohort of GW veterans, whether low-level GB/GE exposure is associated with structural alterations in specific hippocampal subfields, estimated from 4 T MRI. Methods: The Automatic Segmentation of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2-weighted images acquired on a 4 T MR scanner in 56 GW veterans with suspected GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49 +/- 7 years). Results: GB/GE exposed veterans had smaller CA2 (p = 0.003) and CA3/DG (p = 0.01) subfield volumes compared to matched, unexposed GW veterans. There were no group difference in total hippocampal volume, quantified with FreeSurfer, and no dose-response relationship between estimated levels of GB/CF exposure and total hippocampal or subfield volume. Conclusions: These findings extend our previous report of structural alterations in the hippocampi of GW veterans with suspected GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in a different cohort of GW veterans with suspected GB/GF exposure. Published by Elsevier Inc.