Noninvasive tool detects small blood vessel disease in SCD brain
Study: Neurological complication linked to cognitive impairment
Researchers have used an existing noninvasive optical tool that leverages the way light interacts with tissue to detect disease in the small blood vessels in the brain, according to a study. This neurological complication of sickle cell disease (SCD) is linked to cognitive impairment.
Used in a variety of fields, the test leverages near-infrared spectroscopy, or NIRS, an optical tool that uses probes placed on the forehead to measure blood flow in the small blood vessels in the brain.
“The whole motivation is to show that NIRS is reliable and could do more than it’s currently utilized for,” Sossena Wood, PhD, assistant professor of biomedical engineering at Carnegie Mellon University in Pennsylvania, said in a university news story. “I’m excited to be part of improving measurement tools for sickle cell disease progression and, in turn, quality of life for those living with the disease.”
The study, “Assessment of cerebral autoregulation and cerebral perfusion in patients with sickle cell disease using frequency-domain near-infrared spectroscopy,” was published in the Journal of Applied Physiology.
Reliable way to measure changes in small blood vessels of brain needed
In SCD, sickle-shaped red blood cells die off before the body can replace them, resulting in insufficient oxygen delivery to body tissues and symptoms of anemia. The abnormal shape of these cells also causes them to get stuck in small blood vessels, cutting off blood flow and leading to periodic episodes of pain, known as vaso-occlusive crises.
SCD can be diagnosed before or soon after birth, and with treatments starting early, many SCD patients are living longer. With age, however, some SCD patients develop cerebral small vessel disease, a complication marked by reduced blood flow in the small blood vessels in the brain that leads to difficulties with thinking and memory.
Cerebral small vessel disease can be detected via a change in cerebral autoregulation, a process that ensures blood flow in the brain is maintained as blood pressure varies.
However, current methods to assess cerebral autoregulation rely on measuring blood pressure and flow in the larger blood vessels in the body. Thus, finding a reliable way to measure these changes in the smallest blood vessels is still needed.
To address this, the team at Carnegie Mellon, alongside colleagues at the University of Pittsburgh, evaluated whether NIRS can assess cerebral autoregulation and detect small blood vessel disease in SCD.
“Rather than looking only at the larger vessels in adults, our study focused highly on the [blood flow dynamics] associated with blood pressure changes in the smaller vessels, and what NIRS can reliably detect about blood and oxygen changes there,” Wood said.
NIRS measured changes in brain levels of hemoglobin
The study enrolled 13 adults with SCD (nine men and four women), with a mean age of 40.6 years, as well as14 age- and race-matched healthy individuals who served as controls.
Along with a belt across the chest to measure breathing rate and blood pressure cuffs on the arm and finger, the researchers placed two optical probes on the forehead of each participant. While in a dark room, they were asked to breathe at three different rates using a metronome.
NIRS then measured changes in brain levels of hemoglobin, the protein in red blood cells that carries oxygen, with or without bound oxygen. The levels of these two forms of hemoglobin rose and fell with each breath in and out, forming wave-like patterns over time.
“Unlike prior studies done on large vessel abnormalities or at rest, this one measured dynamic cerebral autoregulation and participants’ response during breathing, taking things a step further toward positive utility,” Wood noted.
Data showed that the wave patterns seen in SCD patients for both oxygenated and deoxygenated hemoglobin were significantly different from those of controls, suggesting differences in cerebral autoregulation between the two groups, the team noted. These differences were smaller among patients receiving SCD-directed therapies than in those who were not.
Over time, the ratio of deoxygenated to oxygenated hemoglobin was higher in SCD patients compared with controls, meaning that SCD patients had more deoxygenated and less oxygenated hemoglobin in their brains as they breathed. Likewise, the ratio of oxygenated to total hemoglobin was significantly lower in adults with SCD than in controls, which means that less of their total hemoglobin was bound to oxygen.
The adult sickle cell disease population is very young, and they’re getting older because of the therapies that are helping them live longer.
SCD patients also had longer blood transit times, the time it takes for blood to travel through a specific area in the blood vessel, “indicating reduced blood flow velocity from vaso-occlusion,” the researchers wrote. Patients receiving SCD-directed therapies had shorter blood transit times compared with those who were not.
Modeling studies confirmed that blood transit times were significantly longer in the brain’s capillaries, or the smallest blood vessels, of SCD patients, which corresponded to “slower blood velocities, reduced cerebral blood flow in the microvasculature within the [brain], and reduced capillary [oxygen] saturation,” the researchers wrote.
While cerebral tissue oxygen saturation was lower in SCD patients compared with controls (63.1% vs. 66.1%), the difference was not statistically significant, meaning it could have arisen by chance.
“We present preliminary evidence of the utility of NIRS to monitor [cerebral autoregulation] in SCD,” the team wrote. “NIRS may represent a new screening method for cerebral small vessel disease in SCD.”
There is still much to learn as people with the disease age, Wood said, and NIRS could aid those efforts.
“The adult sickle cell disease population is very young, and they’re getting older because of the therapies that are helping them live longer,” Wood said. “As they age, there is a lot we are learning about the [mechanisms] of the disease, and NIRS is a useful point of care screening tool in environments where sickle cell disease is most prevalent.”
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