A Low-cost Compact Diffuse Speckle Contrast Flow-oximeter for Neonatal Brain Monitoring

Grants and Contracts Details


An estimated 15 million babies are born preterm annually in the world and almost 1 million children die each year due to complications of preterm birth1. These preterm infants are at highest risk for neurologic injuries including hypoxia-ischemia, intraventricular hemorrhage, and white matter injury/periventricular leukomalacia due to their premature brain structures, hemodynamic instability, anemia, and impaired cerebral hemodynamics/metabolism. Unstable cerebral hemodynamics has been found in preterm infants using near-infrared spectroscopy (NIRS) to monitor fluctuations in cerebral oxy- and deoxy-hemoglobin concentrations ([HbO2] and [Hb]) and tissue oxygenation saturation (StO2)2-4. However, NIRS has not yet to be widely accepted into clinical practice, in part because the large intra- and inter-patient variability of StO2 makes it difficult to establish thresholds that would have sufficient predictive value5-7. Consequently, there is a growing interest in alternative methods that can directly measure cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) since these are likely more sensitive biomarkers of brain health than StO2 alone8-10. The recent development of a novel near-infrared diffuse speckle contrast flowmeter (DSCF) in our laboratory provides a low-cost, fast, and portable means for direct monitoring of CBF variations in infants11, 12. DSCF uses a small laser diode and a bare charge-coupled-device (CCD) sensor chip to rapidly quantify spatial speckle fluctuations resulting from moving red blood cells (RBCs) in deep tissues (up to 8 mm). As a result, DSCF allows for the assembly of a tiny probe which can be easily fixed on the small heads of infants for CBF monitoring. DSCF measurements of flow variations have already been validated on head-simulating tissue phantoms and in-vivo adult forearm tissues11, 12. We propose to optimize and extend our novel DSCF (measuring CBF alone) to a diffuse speckle contrast flow-oximeter (DSCFO), which will enable simultaneous measurements of CBF, StO2, and CMRO2 in infants. Measurement of multiple hemodynamic/metabolic variables together will provide better assessment of neonatal brain health than a single parameter alone. In Aim 1, the DSCFO device will be constructed, calibrated, and validated in head-simulating tissue phantoms and in vivo tissues against other established standards. In Aim 2, the optimized DSCFO device will be further examined in clinic to measure CBF, StO2, and CMRO2 in preterm infants diagnosed with patent ductus arteriosus (PDA) who will be undergoing treatment with indomethacin. This treatment group is selected because of the well-known vasoconstricting effects of indomethacin, which provides the opportunity to assess whether the DSCFO can detect the expected variations in CBF and StO2, required to maintain a normal CMRO2. We hypothesize that neonatal cerebral hemodynamics/metabolism altered by the treatment can be safely detected by the DSCFO device, which should reasonably correlate with other standard physiological measures and clinical outcomes. Exploration of these correlations will allow us to further validate the novel DSCFO for clinical use and demonstrate the device’s potential to provide prompt biomarkers for evaluating brain health and treatment effects. Specific Aim 1: Develop, Calibrate, and Validate a Low-cost DSCFO Device (Year 1). The proposed DSCFO probe will consist of two small laser diodes at wavelengths of 690 nm and 830 nm and a tiny inexpensive complementary metal-oxide semiconductor (CMOS) sensor board. Alternative measurements of light intensity changes at the two wavelengths will enable quantification of StO2 variations13. Data will be processed using the algorithms developed in our lab to derive CBF, StO2, and CMRO213-18. In addition, the CMOS pixel array will enable parallel measurements at different regions and depths of the neonatal head for quantifying cerebral hemodynamic/metabolic heterogeneity and reducing partial volume effects from the top layers of scalp and skull17, 18. The DSCFO device will be optimized and calibrated using head-simulating tissue phantoms and will be further validated in adult forearm tissues (reducing potential risk to infants) against standard methods, i.e., NIRS for StO2 and diffuse correlation spectroscopy (DCS) for CBF13-18. Specific Aim 2: Test the Use of DSCFO to Continually Monitor Cerebral Hemodynamic/Metabolic Variations in Preterm Infants with Patent Ductus Arteriosus (PDA) Undergoing Indomethacin Treatment (Year 2). Preterm infants (gestational age < 30 weeks) with hemodynamically significant PDA confirmed by echocardiography will be studied. Acquisition of DSCFO data sets will be coordinated during the pharmacological treatment of PDA, which involves the infusion of intravenous indomethacin over 30 minutes at a dose of 0.2 mg/kg. A small DSCFO sensor will be fixed on infant forehead for continuous monitoring of CBF, StO2, and CMRO213-18 while cerebral blood flow velocity (CBFV) in the middle cerebral artery will be measured intermittently by a small handheld transcranial Doppler (TCD) probe over the study period. We will correlate DSCFO and TCD measurements with other physiological measures and clinical outcomes. We hypothesize that indomethacin treatment will result in global physiological changes (e.g., CBFV, blood pressure, and arterial blood oxygen saturation SaO2), leading to hemodynamic/metabolic variations in local brain tissues detected by DSCFO (i.e., CBF, StO2, and CMRO2). Also, these global and local physiological variations will affect clinical outcomes. Impact: Completion of this study will offer a noninvasive, inexpensive, fast, and portable device for bedside cerebral monitoring of the critically ill infants who are at highest risk for neurological morbidities.
Effective start/end date2/10/181/31/22


  • National Institute of Child Health and Human Develop: $567,506.00


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