Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

The overall goal of this procedure is to assess cerebral oxygen metabolism in newborns at the bedside. This is accomplished by first placing the optical probe on the head and measuring with the frequency domain near infrared spectroscopy or FD nears device cerebral hemoglobin oxygenation at concentration in the underlying brain. Next, using a diffuse correlation spectroscopy or DCS device and index of cerebral blood flow is measured, then the FDIR and DCS measurements are repeated on six other locations covering the frontal, temporal and parietal areas.

Using a pulse co oximeter, systemic parameters like arterial oxygenation and hemoglobin in the blood are then acquired. Finally, all the parameters are combined to calculate oxygen consumption or CM RO two. Ultimately, results can be obtained that show cerebral hemoglobin oxygenation, cerebral blood flow, and cerebral oxygen metabolism across cortical regions to help detect possible brain injury response to therapy or measure brain development.

The main advantage at D CSS over existing methods such as MI and Path is that it provide bedside measure of brain metabolism without any risk to the infant. We use research devices that require some technical expertise and training to operate. We're currently working with Incorporated and other companies to develop full integrated FD near DCS systems that are Easier to use.

This method has the potential to improve neonatal brain health by allowing us to screen for injuries, monitor treatment responses, predict outcomes, and ideally optimize individual care. We first had this idea for this approach when we realized that zero oxygen metabolism as a more precise and accurate measure of neural function than oxygen extraction fraction demonstrating the procedure will be pay. Lynn, Angela Ollio and Catherine Hagen, members of our study team, all of the following demonstration are filmed in the neonatal intensive care unit at Brigham and Women Hospital with the valuable help of the NICU staff.

These recordings are approved by the Partners Healthcare IRB Frequency domain, near infrared spectroscopy and diffuse correlation Spectroscopy comprise a customized frequency domain system from ISS Incorporated with two identical sets of eight laser diodes emitting at eight wavelengths ranging from 660 to 830 nanometers, two photomultiplier tube detectors, and a DCS device, which is a home-built system consisting of a solid state long coherence laser at 785 nanometers and four photon counting avalanche photo diode detectors. Choose the appropriate probe according to the infant's postmenstrual age or PMA. For example, use an optical probe with FD nears source detector separations of one 1.52 and 2.5 centimeters for infants less than 37 weeks PMA and the probe with FD nears separations 1.52, 2.5, and three centimeters for older infants in both probes.

DCS source detector separations are 1.5 and two centimeters, sanitize the probes with a disinfecting wipe and insert the probe and fibers into a single use polypropylene plastic sleeve to meet ANSI standards for skin exposure. The light at the probe is attenuated and diffused across a large area by a white Teflon disc at the bedside. Using a power meter, ensure that the laser power at the probe is less than 25 milliwatts and use an infrared viewing card to verify the spot size is larger than three millimeters in diameter.

Open the ER's gooey and select the prob settings file corresponding to the probe and calibration block being used to adjust detector gains. Gently place the probe on an area of the subject's head without hair and maintain it in the same position without applying any pressure. We prefer to set the gains in the frontal area because this region has the lowest absorption and is therefore the most prone to saturation.

Turn on sources and detectors and adjust the PMT voltage until the amplitude of any of the source lasers reaches 20, 000 counts. Place the probe back on the calibration block and use neutral density filters. If any.

Source detector pair saturates hold the probe still for 16 seconds while running the calibration procedure. Measuring a calibration block of known optical properties allows estimation of coupling factors for each source detector pair. After calibration, acquire 16 seconds of data on the block and use an in-house MATLAB GUI to visually assess the adequacy of the calibration.

The measured absorption and scattering coefficients should match the actual coefficients of the calibration block at all. Wavelengths recalibrate if the fit is poor. For DCS preparation, open the in-house DCS data acquisition MATLAB GUI and load the settings file corresponding to the optical probe being used.

There is no gain adjustment for the DCS detectors. As for the FD nears device, if low counts are noticed, part the hair and reposition the probe to have better light detection. Avoid excessive room light to reduce background noise.

In addition to CBFI and SO two, which will be acquired by the FD nears DCS two systemic parameters, arterial oxygenation and hemoglobin in the blood are needed to calculate cerebral oxygen metabolism. Use a pulse co oximeter to acquire these systemic parameters by attaching an adhesive single use sensor to the infant's big toe or foot SA O2 and HGB will be displayed on the monitor within a few seconds. Measure seven locations covering frontal, temporal, and parietal areas according to a 10 20 system in sequence shown here.

Begin by parting the hair of the infant along the source detector line and place the probe on an area of the head. Next, turn on FD nears lasers and detectors and acquire data for 16 seconds. Then turn on the DCS laser and detectors and acquire data for 10 seconds.

Repeat FD nears DCS measurements up to three times in each location. Repositioning the probe in a slightly different spot for each acquisition. This is done to minimize the effect of local in homogeneity such as hair and superficial large vessels, and to provide values representative of a region rather than a single spot for data analysis.

Open an in-house post-processing data analysis MATLAB script. This software not only estimates all hemodynamic parameters, but also uses the redundancy of data to automatically assess measurement quality and constrain results. Calculate absolute HBO and HBR concentrations by fitting the absorption coefficients at all wavelengths, using literature values for HB extinction coefficients and a 75%concentration of water in tissue derive total hemoglobin concentration and hemoglobin oxygen saturation from HBO and HBR concentrations.

Estimate the cerebral blood volume using the molecular weight of hemoglobin and the brain tissue density. Calculate the blood flow index or CBFI by fitting the measured temporal auto correlation functions to the diffusion correlation equation. Finally, calculate the index of cerebral oxygen consumption by using the FD nears measure of SO two and the DCS measure of CBFI with the following equation.

As shown here, a cross-sectional study on more than 50 healthy infants revealed that while CBV more than doubles during the first year of life, SO two remains constant. A study on 70 healthy newborns also demonstrated that C-B-V-C-B-F-I and CMR O2 I are higher in temporal and parietal regions than in the frontal region, which is consistent with pet glucose uptake findings. In both of our studies, the constant SO two indicates that oxygen delivery closely matches local consumption while C-B-V-C-B-F and CM O2 are more tightly coupled with neural development.

To verify that CM RO two I is a better screening tool than SO two. In detecting neonatal brain injury studies in brain injured infants demonstrate that SO two is not significantly altered by brain injury in both early and chronic stages. While CMR O2 I is significantly different than normal during both the acute and chronic stages to verify hypothermia therapy reduces damage after hypoxic insult by lowering brain metabolism.

We measured 10 infants during therapy and compared them to normal controls. As shown here, the CMR O2 I of infants treated with therapeutic hypothermia significantly decreases to levels below normal. These preliminary results suggest that the FD nears DCS method may be able to guide and optimize hypothermia therapy once mastered.

This technique can be performed efficiently at the bedside without disturbing the infant. To ensure optimal data quality, it's important to maintain good contact between the probe and the infant's head during acquisition. After watching this video, you should have a good understanding of how to perform measures of cerebral metabolism and hemodynamics in infants.