Multi-wavelength multi-distance diffuse correlation spectroscopy system for assessment of premature infants' cerebral hemodynamics.

Infants born at an extremely low gestational age (ELGA, < 29 weeks) are at an increased risk of intraventricular hemorrhage (IVH), and there is a need for standalone, safe, easy-to-use tools for monitoring cerebral hemodynamics. We have built a multi-wavelength multi-distance diffuse correlation spectroscopy device (MW-MD-DCS), which utilizes time-multiplexed, long-coherence lasers at 785, 808, and 853 nm, to simultaneously quantify the index of cerebral blood flow (CBFi) and the hemoglobin oxygen saturation (SO2). We show characterization data on liquid phantoms and demonstrate the system performance on the forearm of healthy adults, as well as clinical data obtained on two preterm infants.

Comparing the performance potential of speckle contrast optical spectroscopy and diffuse correlation spectroscopy for cerebral blood flow monitoring using Monte Carlo simulations in realistic head geometries.

Significance: The non-invasive measurement of cerebral blood flow based on diffuse optical techniques has seen increased interest as a research tool for cerebral perfusion monitoring in critical care and functional brain imaging. Diffuse correlation spectroscopy (DCS) and speckle contrast optical spectroscopy (SCOS) are two such techniques that measure complementary aspects of the fluctuating intensity signal, with DCS quantifying the temporal fluctuations of the signal and SCOS quantifying the spatial blurring of a speckle pattern. With the increasing interest in the use of these techniques, a thorough comparison would inform new adopters of the benefits of each technique. Aim: We systematically evaluate the performance of DCS and SCOS for the measurement of cerebral blood flow. Approach: Monte Carlo simulations of dynamic light scattering in an MRI-derived head model were performed. For both DCS and SCOS, estimates of sensitivity to cerebral blood flow changes, coefficient of variation of the measured blood flow, and the contrast-to-noise ratio of the measurement to the cerebral perfusion signal were calculated. By varying complementary aspects of data collection between the two methods, we investigated the performance benefits of different measurement strategies, including altering the number of modes per optical detector, the integration time/fitting time of the speckle measurement, and the laser source delivery strategy. Results: Through comparison across these metrics with simulated detectors having realistic noise properties, we determine several guiding principles for the optimization of these techniques and report the performance comparison between the two over a range of measurement properties and tissue geometries. We find that SCOS outperforms DCS in terms of contrast-to-noise ratio for the cerebral blood flow signal in the ideal case simulated here but note that SCOS requires careful experimental calibrations to ensure accurate measurements of cerebral blood flow. Conclusion: We provide design principles by which to evaluate the development of DCS and SCOS systems for their use in the measurement of cerebral blood flow.

Open-source FlexNIRS: A low-cost, wireless and wearable cerebral health tracker.

Currently, there is great interest in making neuroimaging widely accessible and thus expanding the sampling population for better understanding and preventing diseases. The use of wearable health devices has skyrocketed in recent years, allowing continuous assessment of physiological parameters in patients and research cohorts. While most health wearables monitor the heart, lungs and skeletal muscles, devices targeting the brain are currently lacking. To promote brain health in the general population, we developed a novel, low-cost wireless cerebral oximeter called FlexNIRS. The device has 4 LEDs and 3 photodiode detectors arranged in a symmetric geometry, which allows for a self-calibrated multi-distance method to recover cerebral hemoglobin oxygenation (SO2) at a rate of 100 Hz. The device is powered by a rechargeable battery and uses Bluetooth Low Energy (BLE) for wireless communication. We developed an Android application for portable data collection and real-time analysis and display. Characterization tests in phantoms and human participants show very low noise (noise-equivalent power <70 fW/√Hz) and robustness of SO2 quantification in vivo. The estimated cost is on the order of $50/unit for 1000 units, and our goal is to share the device with the research community following an open-source model. The low cost, ease-of-use, smart-phone readiness, accurate SO2 quantification, real time data quality feedback, and long battery life make prolonged monitoring feasible in low resource settings, including typically medically underserved communities, and enable new community and telehealth applications.

Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling.

Significance: Contamination of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow (CBF) due to systemic physiology remains a significant challenge in the clinical translation of DCS for neuromonitoring. Tunable, multi-layer Monte Carlo-based (MC) light transport models have the potential to remove extracerebral flow cross-talk in cerebral blood flow index ( CBF i ) estimates. Aim: We explore the effectiveness of MC DCS models in recovering accurate CBF i changes in the presence of strong systemic physiology variations during a hypercapnia maneuver. Approach: Multi-layer slab and head-like realistic (curved) geometries were used to run MC simulations of photon propagation through the head. The simulation data were post-processed into models with variable extracerebral thicknesses and used to fit DCS multi-distance intensity autocorrelation measurements to estimate CBF i timecourses. The results of the MC CBF i values from a set of human subject hypercapnia sessions were compared with CBF i values estimated using a semi-infinite analytical model, as commonly used in the field. Results: Group averages indicate a gradual systemic increase in blood flow following a different temporal profile versus the expected rapid CBF response. Optimized MC models, guided by several intrinsic criteria and a pressure modulation maneuver, were able to more effectively separate CBF i changes from scalp blood flow influence than the analytical fitting, which assumed a homogeneous medium. Three-layer models performed better than two-layer ones; slab and curved models achieved largely similar results, though curved geometries were closer to physiological layer thicknesses. Conclusion: Three-layer, adjustable MC models can be useful in separating distinct changes in scalp and brain blood flow. Pressure modulation, along with reasonable estimates of physiological parameters, can help direct the choice of appropriate layer thicknesses in MC models.

Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain.

Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO(2)) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BF(ix)) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO(2) and CBV, relative values of BF(ix), and relative cerebral metabolic rate of oxygen (rCMRO(2)) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO(2) correlates with chronological age (r=-0.54, P value ≤0.001) but not with PMA (r=-0.07), whereas BF(ix) and rCMRO(2) correlate better with PMA (r=0.37 and 0.43, respectively, P value ≤0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO(2) are more accurate biomarkers of the brain development than SO(2) in the premature newborns.

Assessment of the frequency-domain multi-distance method to evaluate the brain optical properties: Monte Carlo simulations from neonate to adult.

The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult. For each age, we determined the optimal set of source-detector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8-24% in neonates and infants, while the error increased to 19-44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults.

Assessment of infant brain development with frequency-domain near-infrared spectroscopy.

This is the first report to demonstrate quantitative monitoring of infant brain development with frequency-domain near-infrared spectroscopy (FD-NIRS). Regionally specific increases in blood volume and oxygen consumption were measured in healthy infants during their first year. The results agree with prior PET and SPECT reports; but, unlike these methods, FD-NIRS is portable and uses nonionizing radiation. Further, new information includes the relatively constant tissue oxygenation with age and location, suggesting a tight control between local oxygen delivery and consumption in healthy infants during brain development. FD-NIRS could become the preferred clinical tool for quantitatively assessing infant brain development.

Noninvasive measurement of neuronal activity with near-infrared optical imaging.

Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and noninvasively measuring neuronal and vascular signals in the brain with temporal resolution of up to 1 ms. However, while optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the so-called fast signal) is just emerging and requires further optimization and validation. In this work, we present preliminary studies in which we measured the fast signal in 10 healthy volunteers during finger-tapping, tactile stimulation, and electrical median nerve stimulation. We used an instrument (CW4) with 8 source (690 and 830 nm) and 16 detector positions-more optodes than the instruments in previously reported studies. This allowed us to record the ipsilateral and contralateral sensorimotor cortex simultaneously, while at the same time measuring the evoked hemodynamic response. We used an acquisition time of 25 ms per image; after averaging approximately 1000 events, the signal-to-noise ratio was approximately 10(4). Since the expected relative intensity changes due to the fast signal (approximately 10(-3)) are smaller than the relative intensity changes due to physiological effects (approximately 10(-1)), we enhanced the suppression of competing signals such as the heartbeat-associated intensity changes, and established five criteria with which to assess the robustness of the fast signal. We detected the fast signal in 43% of the measurements during finger-tapping, 60% of those during tactile stimulation, and 23% of those during electrical median nerve stimulation. The relative changes in intensity associated with the fast signal were approximately 0.07% and the latency of the signal was approximately 100 ms.

Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters.

Near-infrared spectroscopy (NIRS) can be used to noninvasively measure changes in the concentrations of oxy- and deoxyhemoglobin in tissue. We have previously shown that while global changes can be reliably measured, focal changes can produce erroneous estimates of concentration changes (NeuroImage 13 (2001), 76). Here, we describe four separate sources for systematic error in the calculation of focal hemoglobin changes from NIRS data and use experimental methods and Monte Carlo simulations to examine the importance and mitigation methods of each. The sources of error are: (1). the absolute magnitudes and relative differences in pathlength factors as a function of wavelength, (2). the location and spatial extent of the absorption change with respect to the optical probe, (3). possible differences in the spatial distribution of hemoglobin species, and (4). the potential for simultaneous monitoring of multiple regions of activation. We found wavelength selection and optode placement to be important variables in minimizing such errors, and our findings indicate that appropriate experimental procedures could reduce each of these errors to a small fraction (<10%) of the observed concentration changes.