Noninvasive optical assessment of resting-state cerebral blood flow in children with sickle cell disease

Abstract

Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro-and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children <6 year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex-and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls (p < 0.001). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels (p ¼ 0.012), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD (n ¼ 7), DCSmeasured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery (R s ¼ 0.68), although the trend was not statistically significant (p ¼ 0.11). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.

Quantifying the Cerebral Hemometabolic Response to Blood Transfusion in Pediatric Sickle Cell Disease With Diffuse Optical Spectroscopies

“…Further, OEF, CBF i , and CBV were significantly inversely associated with hemoglobin concentration, and these associations persisted after accounting for the influence of age and sex (Table 4). While our changes in OEF largely agree with previous reports (11,12), the decreases in CBF i that we measured were larger than expected (26). We hypothesize that the origin of these differences is due to the confounding influence of hematocrit (28) and work is ongoing to develop correction factors that account for this influence.…”

“…When FDNIRS data was available, measured µ a and µ ′ s at 852 nm were incorporated into the fit for CBF i . When unavailable (as was the case in 2 measurements), µ a and µ ′ s were assumed to be 0.16 cm −1 and 8.4 cm −1 , respectively (26). Fits were discarded if ǫ > 14% where ǫ = i (g 2, fit (τ i ) − g 2, meas (τ i ))/g 2, fit (τ i ) × 100%.…”

Cerebrovascular reactivity measured in awake mice using diffuse correlation spectroscopy

“…The DCS instrument employed herein consisted of an 852-nm long coherence-length laser (iBeam smart, TOPTICA Photonics, Farmington, NY), an array of four photon counting avalanche photodiodes (SPCM-AQ4C-IO, Perkin-Elmer, Quebec, Canada), and a hardware autocorrelator board (Flex05-8ch, 49 NJ). 33 , 50 The animal interface for the device consisted of a custom 3D printed optical sensor with a multimode source fiber (FT-400-EMT, Thorlabs Inc., Newton, NJ, USA) and four single-mode detector fibers (780HP, Thorlabs Inc., Newton, NJ, USA) spaced 3 and 4.5 mm from the source [ Figs. 1(a) and 1(c) ].…”

Intracranial Sensors for Continuous Monitoring of Neurophysiology

“…However, the current DCS technology is restricted in depth and spatial sensitivity that affects deep brain tissue perfusion. [ 133 ] Recently, a fiber‐less diffuse speckle contrast flowmeter has been proven to provide a low‐cost, simple, and flexible approach to continuous monitoring of CBF variations in deep tissues through the intact scalp and skull. [ 134 ] In comparison with DCS that has rigid optical fiber bundles, this diffuse speckle contrast flowmeter contains soft electrical wires, which could be integrated with wearable sensors for continuous monitoring of free‐moving animals.…”