Whole-body imaging links heart, brain inflammation after MI

A new study using whole-body molecular imaging identified a shared inflammatory response between the cardiovascular and central nervous systems following myocardial infarction (MI), possibly adding insight to the reported connection between cardiac injury and cognitive decline.

Researchers induced MI in 43 mice and compared them to a control group. Each subject underwent serial whole-body positron emission tomography (PET) imaging of the mitochondrial translocator protein (TSPO), a marker of inflammation.

Lead author James T. Thackeray, PhD, with Hannover Medical School in Germany, and colleagues reported TSPO signals in the brain and myocardium were elevated one week after infarction compared with the control mice. After stepwise declines in TSPO thereafter, a second wave of inflammation occurred in both systems at 4 weeks as the mice developed progressive heart failure.

A substudy of three human patients showed similar inflammatory responses four to six days after acute ST-segment elevation MI.

“TSPO-targeted whole-body molecular imaging identifies inflammation as a crucial connection between the brain and heart after cardiac injury,” Thackeray and colleagues wrote in the Journal of the American College of Cardiology. “Acute MI leads to an early inflammatory response, which stimulates adverse left ventricular remodeling and triggers brain microglia activation in a biphasic pattern. A systems-based, multiorgan molecular imaging strategy may assist in the development of targeted anti-inflammatory therapies that may benefit both systems by providing risk assessment, identifying therapeutic target expression, and monitoring intervention effectiveness.”

The researchers pointed out cognitive function wasn’t measured in their study, but previous research has shown neuroinflammation negatively affects cognitive function and has been associated with the progression of Alzheimer’s disease.

In an accompanying editorial, Y. Chandrashekhar, MD, and Jagat Narula, MD, PhD, said Thackeray et al.’s study shows heart damage “may specifically mediate concurrent brain inflammation that could, intuitively, lead to adverse brain outcomes.”

It also demonstrates the “tremendous potential” of imaging techniques to identify other important connections between organs.

“Whole-body TSPO PET imaging allowed concurrent detection of inflammatory changes in multiple organs (heart, spleen, bone marrow, brain, and kidney) and allowed serial evaluation for temporal changes,” Chandrashekar and Narula wrote. “One could presumably detect and serially follow vascular inflammation that can portend adverse outcome, possibly with whole-body TSPO PET in high-risk coronary artery disease patients. Such studies will allow us to understand the intricate interplay between interconnected pathological circuits such as heart–brain, gut–brain, or chronic infection (such as HIV)–brain interactions.”

These interactions, the editorialists wrote, could lead to better understanding of clinical trial results and the development of more targeted treatments.