Is the eye the window to the brain? How gadolinium is changing the field of cerebrovascular imaging

Gadolinium could be doing a lot more for cerebrovascular patients than previously thought. According to a group of researchers at the National Institutes for Health, the chemical agent could highlight not just abnormalities in routine brain MRIs, but identify the severity of incident stroke.

Gadolinium has long played a critical role in clinicians’ understanding of pathologic processes, and that will likely continue to be the case, senior author Richard Leigh, MD, and colleagues wrote in Neurology this week. Though the chemical might be commonplace in the clinical setting, Leigh said the ties between the agent, eye health and stroke indicators was surprising.

“We suspected there may be a link between the stroke and the eye,” Leigh told Radiology Business. “However, to find that the eye was informative about the stroke was exciting.”

Gadolinium is routinely administered in imaging procedures to expose brain abnormalities during MRI scans. In a healthy patient, the chemical is filtered out of the bloodstream through the kidneys; in those who have experienced damage to their blood-brain barriers, it leaks into the brain, drawing attention to brain damage and highlighting problem source areas.

“We have been conducting a large observational natural history study at the NIH for many years in which we collect serial brain imaging on stroke patients to learn more about the disease,” Leigh said. “When reviewing the images from this study, we noticed that there was leakage of gadolinium into the eyes in some cases and that prompted us to construct this investigational study to better understand the phenomenon.”

Leigh and his team performed MRI scans on 167 stroke patients upon admission to the hospital, withholding gadolinium from initial tests, the study stated. They then compared those results to fresh MRI scans taken two and 24 hours later with the addition of gadolinium.

Around three-quarters of patients experienced gadolinium leakage into their eyes during testing, the authors reported. Two-thirds (66 percent) showed leakage in the two-hour scan, while 75 percent presented with leakage at the 24-hour MRI.

“There was an element of surprise surrounding the initial observation, given that it had not been previously described,” Leigh said. “However, when we carried out this study to explore the finding in more detail, the surprises kept coming. I did not anticipate that this process occurring in the eye would be so revealing about acute and chronic cerebrovascular disease of the brain.”

The distribution of gadolinium within the eye varied between MRI scans, Leigh said—in patients who showed traces of the chemical at the two-hour mark, gadolinium was largely present in the front area of the eye, known as the aqueous chamber. At 24-hour scans, gadolinium seemed to migrate toward a patient’s vitreous chamber, at the back of the eye.

According to Leigh et al.’s study, stroke patients who recorded gadolinium in their vitreous chamber at the 24-hour mark were more likely to be older, have a history of hypertension and have more white matter hyperintensities—which are linked to decreased cognitive function and brain aging—in their MRIs.

“The key finding is that a focal process in the brain, specifically the stroke, appears to be having a remote effect on the eye,” Leigh said. “This supports the concept that stroke has both local and diffuse effects on the body. From a technology perspective, these findings suggest that there may be a way to evaluate stroke in the brain via the eye with an as-of-yet not developed technology.”

The concept is promising, he said, and clinicians’ next step will likely be moving to a contrast agent that can be visualized without an MRI. Gadolinium is transparent and doesn’t harm a patient’s vision, but it does require large-scale testing like magnetic resonance to be effective.

Leigh said before anything else can happen, the research team needs to confirm their current results with a prospective study including both control subjects and patients with disorders beyond stroke—multiple sclerosis, for example.

“Such a study would incorporate systematic examination of the eyes and vision,” he said. “In addition, modern ophthalmological techniques that might confirm the breakdown in the blood-ocular barrier, including optical coherence tomography and Fluorescein angiography, could be applied. The results of such a study would aim to determine which ocular evaluation can provide a sensitive and specific measure of the stroke.”