Better Screening Tool for Sickle Cell Disease Progression

Near-infrared spectroscopy (NIRS), an optical tool that leverages light-tissue interaction to measure changes in hemoglobin concentration and oxygenation, has been used in a variety of fields due to its ability to measure tissue oxygenation and blood flow non-invasively. In a new study led by Carnegie Mellon University and University of Pittsburgh researchers, NIRS was investigated as a screening tool for adults with sickle cell disease to assess not only oxygenation changes, but also the underlying mechanisms associated with aging with the disease.

Sickle cell disease significantly affects and disrupts oxygenation in the body and its impact on the brain has been understudied. As individuals with sickle cell disease age, they can develop problems with small blood vessels in the brain, leading to reduced blood flow and difficulties with thinking, memory, and other functions that might impact their quality of life. One marker of cerebral small vessel disease, a neurological complication of sickle cell disease that increases with age, is cerebral autoregulation. Cerebral autoregulation ensures that blood flow is maintained or controlled as blood pressure varies.

Current methods to assess cerebral autoregulation are largely accomplished through the measuring of pressure and flow from the body’s larger vessels, for example, using a blood cuff on the arm or a transcranial doppler ultrasound. A significant drawback is that transcranial doppler ultrasound measurements have poor blood flow measurements in adults and do not report oxygenation. Furthermore, finding a reliable way to measure blood and oxygen changes in the body’s smallest vessels has presented an ongoing challenge.

To address this, researchers led the first study to monitor cerebral autoregulation in sickle cell disease using NIRS, while highlighting NIRS as an important screening tool for cerebral small vessel disease in adults with sickle cell disease.

“Rather than looking only at the larger vessels in adults, our study focused highly on the hemodynamics associated with blood pressure changes in the smaller vessels, and what NIRS can reliably detect about blood and oxygen changes there,” noted Sossena Wood, assistant professor of biomedical engineering at Carnegie Mellon. “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.”

Systematically aligning all study participants, whether they were controls or adults, to breathe at the same rate was an important consideration noted in the Journal of Applied Physiology paper. From there, with NIRS measurements and an advanced mathematical tool, researchers could extract important measurements about blood flow, transit times, and changes in the microvascular level that current measurement tools lack.

This research has also been foundational for work Wood’s group is doing abroad, in partnership with Carnegie Mellon University Africa and University of Pittsburgh Medical Center’s Adult Sickle Cell Center for Excellence.

In Nigeria, they are participating in a clinical trial with colleagues from Pitt and Lagos University Teaching Hospital, where sickle cell disease patients are administered an affordable medication, erythropoietin, that boosts hemoglobin levels. With NIRS, they have been able to track blood and oxygen changes in tiny vessels, finding that the medication led to higher oxygen levels in patients after each dosage. Observed wins like this could lead to greater adoption by clinicians and the hematologist community.

“The whole motivation is to show that NIRS is reliable and could do more than it’s currently utilized for,” said Wood. “The adult sickle cell disease population is very young, and they’re getting older because of the therapies that are helping them live longer. As they age, there is a lot we are learning about the pathology of the disease and NIRS is a useful point of care screening tool in environments where sickle cell disease is most prevalent. 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.”

This research was funded in part by the National Institutes of Health and the University of Pittsburgh’s CTSI Research Across the Lifespan pilot program. Carnegie Mellon faculty member Jana Kainerstorfer was an additional collaborator.