Haley's MRI Digs Deeper into Brain Dysfunction in Gulf War Veterans

SOURCE:  Health Imaging, http://www.healthimaging.com/index.php?option=com_articles&article=29479

Radiology: Advanced MRI unlocks mystery of Gulf War syndromes

ASL perfusion imaging slab position. The oblique coronal ASL imaging sections were positioned to cover the head of the hippocampus, with the inferior edge of the imaging slab parallel to the longitudinal anteroposterior axis of the hippocampus and tangent to the gyrus of the temporal lobe, by using T1-weighted high-spatialresolution anatomic images for accurate reference. Source: Radiology.

After nearly two decades of trial and error, researchers leveraged arterial spin labeling (ASL) perfusion MRI and physostigmine challenge to demonstrate persistent and worsening chronic hippocampal dysfunction in the brains of veterans with Gulf War syndromes, according to a study published online Sept. 13 in Radiology. 

“We’re dealing with a very complicated disease. All of the simplistic studies failed,” Robert W. Haley, MD, chief of epidemiology in the departments of internal medicine and clinical sciences at the University of Texas Southwestern Medical Center in Dallas, told Health Imaging in an interview.

The researchers determined that abnormal cerebral blood flow continued or worsened over the 11-year span since initial diagnosis with SPECT. “We also [found ASL MRI with physostigmine challenge] better diagnoses and distinguishes between the three main types of Gulf War illness,” Haley said, describing the find as “a home run.”

Gulf War illness is a poorly understood chronic condition associated with exposure to neurotoxic chemicals and nerve gas. It affects an estimated 25 percent of the 700,000 military personnel deployed to the 1991 Persian Gulf War, according to the U.S. Department of Veterans Affairs’ scientific advisory committee.

The three main syndromes associated with Gulf War illness produce a variety of symptoms. Syndrome 1 is associated with memory problems, syndrome 3 with chronic pain and syndrome 2, the most severe, with severe confusion, balance disturbances and a host of neurological symptoms.

In 1998, Haley’s research team used SPECT to demonstrate abnormal blood flow in the hippocampi of veterans with Gulf War syndrome, illustrating that the condition is not psychological.

Since the initial study, the research team has investigated other methods to measure the disease. “We finally hit on something that looks like it’s important,” Haley said.

In the current study, the researchers used ASL MRI to assess hippocampal regional cerebral blood flow in 13 control participants and 35 patients with Gulf War syndromes 1, 2 and 3.

Each patient received intravenous infusions of saline in an initial session, and physostigmine in a second session 48 hours later. Physostigmine is a short-acting cholinesterase inhibitor, used to test the functional integrity of the cholinergic system, a neurotransmitter system involved in the regulation of memory and learning.

“ASL scanning after giving this medication is particularly well suited to diagnosing Gulf War illness, because it picks up brain abnormalities too subtle for regular MRI to detect,” co-author Richard W. Briggs, PhD, professor of radiology at UT Southwestern, said in a statement. “This allows us to make the diagnosis in a single two-hour session without the need for exposure to ionizing radiation.”

ASL, said Haley, offers multiple advantages over SPECT. “We need to milk every bit of power out of imaging studies because the differences between veterans with Gulf War syndrome and healthy veterans are subtle. ASL MRI provides higher resolution images and more precision than SPECT.”

The findings replicated the results of the initial SPECT study of largely the same group of veterans. The results showed that abnormal hippocampal blood flow persisted and may have progressed 11 years after initial testing and nearly 20 years after the Gulf War, suggesting chronic alteration of hippocampal blood flow.

Physostigmine significantly decreased regional cerebral blood flow (rCBF) in control participants and veterans with syndrome 1, but significantly increased rCBF in the right hippocampus of veterans with syndrome 2 in the original study. The abnormal increase in rCBF was now found to have progressed to the left hippocampus with syndrome 2 and to both hippocampi of the veterans with syndrome 3.

“This suggests a progressive illness,” said Haley.

“Having an objective diagnostic test allows researchers to identify ill veterans for future clinical trials to test possible treatments,” Haley said. “It is also critical for ongoing genomic studies to see why some people are affected by chemical exposures, and why others are not.”

The researchers have replicated the ASL studies in a national sample of Gulf War veterans and are beginning to analyze the data to determine if the results are generalizable outside of the initial battalion studied in the 1998 and recent ASL study, Haley said.