The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease.

ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

Efficient Data Gathering in 3D Linear Underwater Wireless Sensor Networks Using Sink Mobility.

Due to the unpleasant and unpredictable underwater environment, designing an energy-efficient routing protocol for underwater wireless sensor networks (UWSNs) demands more accuracy and extra computations. In the proposed scheme, we introduce a mobile sink (MS), i.e., an autonomous underwater vehicle (AUV), and also courier nodes (CNs), to minimize the energy consumption of nodes. MS and CNs stop at specific stops for data gathering; later on, CNs forward the received data to the MS for further transmission. By the mobility of CNs and MS, the overall energy consumption of nodes is minimized. We perform simulations to investigate the performance of the proposed scheme and compare it to preexisting techniques. Simulation results are compared in terms of network lifetime, throughput, path loss, transmission loss and packet drop ratio. The results show that the proposed technique performs better in terms of network lifetime, throughput, path loss and scalability.

On Reliable and Efficient Data Gathering Based Routing in Underwater Wireless Sensor Networks.

This paper presents cooperative routing scheme to improve data reliability. The proposed protocol achieves its objective, however, at the cost of surplus energy consumption. Thus sink mobility is introduced to minimize the energy consumption cost of nodes as it directly collects data from the network nodes at minimized communication distance. We also present delay and energy optimized versions of our proposed RE-AEDG to further enhance its performance. Simulation results prove the effectiveness of our proposed RE-AEDG in terms of the selected performance matrics.

Stand-alone segmentation of blood flow pulsatility measured with diffuse correlation spectroscopy.

We present a stand-alone blood flow index (BFI) pulse segmentation method for diffuse correlation spectroscopy that uses a wavelet-based representation of the BFI signal at the cardiac frequency in place of an exogenous physiological reference. We use this wavelet-based segmentation method to quantify BFI waveform morphology in a cohort of 30 healthy adults. We demonstrate that the waveform morphology features obtained with the wavelet approach strongly agree with those obtained using an exogenous blood pressure reference signal. These results suggest the promise of stand-alone wavelet-based BFI segmentation for quantifying BFI waveform morphological features.

Impaired cerebrovascular reactivity in pediatric sickle cell disease using diffuse correlation spectroscopy.

Cerebrovascular reactivity (CVR), defined as the ability of cerebral vasculature to dilate in response to a vasodilatory stimulus, is an integral mechanism in brain homeostasis that is thought to be impaired in sickle cell disease (SCD). This study used diffuse correlation spectroscopy and a simple breath-hold stimulus to quantify CVR non-invasively in a cohort of 12 children with SCD and 14 controls. Median [interquartile range] CVR was significantly decreased in SCD compared to controls (2.03 [1.31, 2.44] versus 3.49 [3.00, 4.11] %/mmHg, p = 0.028). These results suggest DCS may provide a feasible means to routinely monitor CVR impairments in pediatric SCD.

Normative cerebral microvascular blood flow waveform morphology assessed with diffuse correlation spectroscopy.

Microvascular cerebral blood flow exhibits pulsatility at the cardiac frequency that carries valuable information about cerebrovascular health. This study used diffuse correlation spectroscopy to quantify normative features of these waveforms in a cohort of thirty healthy adults. We demonstrate they are sensitive to changes in vascular tone, as indicated by pronounced morphological changes with hypercapnia. Further, we observe significant sex-based differences in waveform morphology, with females exhibiting higher flow, greater area-under-the-curve, and lower pulsatility. Finally, we quantify normative values for cerebral critical closing pressure, i.e., the minimum pressure required to maintain flow in a given vascular region.